PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (35)
 

Clipboard (0)
None

Select a Filter Below

Year of Publication
more »
1.  Effect of total disc replacement on atypical symptoms associated with cervical spondylosis 
European Spine Journal  2013;22(7):1553-1557.
Purpose
To determine the efficacy of total disc replacement (TDR) for the treatment of cervical spondylosis associated with atypical symptoms.
Methods
In this retrospective study, patients with myelopathy and/or radiculopathy related to cervical spondylosis that were treated with TDR were contacted by phone. Atypical symptoms involved in the questionnaire included dizziness, headache, nausea, vomiting, blurred vision, tinnitus, palpitations, hypomnesia, and abdominal discomfort. The severity of each atypical symptom was evaluated separately based on an numerical rating scale. The radiographs and charts before and after the surgery were reviewed. Paired samples t tests were used to compare the severity of the symptoms before and after surgery.
Results
Between 2003 and 2010, 73 of 133 patients diagnosed with cervical spondylotic myelopathy and/or radiculopathy treated by TDR experienced atypical symptoms before surgery. The mean follow-up was 34.6 months. There were 47 males and 26 females (mean age 48.9 years). Of the 73 patients, 41 were diagnosed with myelopathy; 13 with radiculopathy; and 19 with mixed-type spondylosis. The incidence of each symptom before surgery was dizziness (46.6 %), tinnitus (41.1 %), facial flushing and sweating (41.1 %), palpitations (39.7 %), headache (35.6 %), hypomnesia (30.1 %), nausea and vomiting (20.5 %), blurred vision (20.5 %), and gastroenterologic discomfort (5.5 %). The severity of the following symptoms improved after surgery: dizziness (p = 0.000, α = 0.05), headache (p = 0.000, α = 0.05), nausea and vomiting (p = 0.000, α = 0.05), blurred vision (p = 0.004, α = 0.05), tinnitus (p = 0.000, α = 0.05), palpitations (p = 0.000, α = 0.05), hypomnesia (p = 0.010, α = 0.05), and other symptoms (p = 0.030, α = 0.05). The gastroenterologic discomfort did not improve (p = 0.731, α = 0.05).
Conclusions
TDR may have a positive effect on atypical symptoms associated with cervical spondylotic myelopathy and/or radiculopathy.
doi:10.1007/s00586-013-2785-6
PMCID: PMC3698341  PMID: 23653130
Cervical spondylosis; Atypical symptoms; Total disc replacement
2.  Delivery Induced Intraperitoneal Rupture of a Cystic Ovarian Teratoma and Associated Chronic Chemical Peritonitis 
Case Reports in Radiology  2014;2014:189409.
Intraperitoneal rupture of cystic ovarian teratoma is a rare complication. We report a case in a 29-year-old female, with increased abdominal circumference 2 months after vaginal delivery. MRI/CT raised this diagnosis associated to chemical peritonitis. A malignant ovarian mass with peritoneal carcinomatosis was excluded. Laparoscopic oophorectomy was performed and histologic analysis confirmed imaging findings. This case demonstrates the interest of imaging before surgery in pelvic masses to avoid misdiagnosing and to provide adequate treatment.
doi:10.1155/2014/189409
PMCID: PMC3972939  PMID: 24744942
3.  Neural networks using two-component Bose-Einstein condensates 
Scientific Reports  2013;3:2531.
The authors previously considered a method of solving optimization problems by using a system of interconnected network of two component Bose-Einstein condensates (Byrnes, Yan, Yamamoto New J. Phys. 13, 113025 (2011)). The use of bosonic particles gives a reduced time proportional to the number of bosons N for solving Ising model Hamiltonians by taking advantage of enhanced bosonic cooling rates. Here we consider the same system in terms of neural networks. We find that up to the accelerated cooling of the bosons the previously proposed system is equivalent to a stochastic continuous Hopfield network. This makes it clear that the BEC network is a physical realization of a simulated annealing algorithm, with an additional speedup due to bosonic enhancement. We discuss the BEC network in terms of neural network tasks such as learning and pattern recognition and find that the latter process may be accelerated by a factor of N.
doi:10.1038/srep02531
PMCID: PMC3757363  PMID: 23989391
4.  The complete mitochondrial genomes of two rice planthoppers, Nilaparvata lugens and Laodelphax striatellus: conserved genome rearrangement in Delphacidae and discovery of new characteristics of atp8 and tRNA genes 
BMC Genomics  2013;14:417.
Background
Nilaparvata lugens (the brown planthopper, BPH) and Laodelphax striatellus (the small brown planthopper, SBPH) are two of the most important pests of rice. Up to now, there was only one mitochondrial genome of rice planthopper has been sequenced and very few dependable information of mitochondria could be used for research on population genetics, phylogeographics and phylogenetic evolution of these pests. To get more valuable information from the mitochondria, we sequenced the complete mitochondrial genomes of BPH and SBPH. These two planthoppers were infected with two different functional Wolbachia (intracellular endosymbiont) strains (wLug and wStri). Since both mitochondria and Wolbachia are transmitted by cytoplasmic inheritance and it was difficult to separate them when purified the Wolbachia particles, concomitantly sequencing the genome of Wolbachia using next generation sequencing method, we also got nearly complete mitochondrial genome sequences of these two rice planthoppers. After gap closing, we present high quality and reliable complete mitochondrial genomes of these two planthoppers.
Results
The mitogenomes of N. lugens (BPH) and L. striatellus (SBPH) are 17, 619 bp and 16, 431 bp long with A + T contents of 76.95% and 77.17%, respectively. Both species have typical circular mitochondrial genomes that encode the complete set of 37 genes which are usually found in metazoans. However, the BPH mitogenome also possesses two additional copies of the trnC gene. In both mitochondrial genomes, the lengths of the atp8 gene were conspicuously shorter than that of all other known insect mitochondrial genomes (99 bp for BPH, 102 bp for SBPH). That two rearrangement regions (trnC-trnW and nad6-trnP-trnT) of mitochondrial genomes differing from other known insect were found in these two distantly related planthoppers revealed that the gene order of mitochondria might be conservative in Delphacidae. The large non-coding fragment (the A+T-rich region) putatively corresponding responsible for the control of replication and transcription of mitochondria contained a variable number of tandem repeats (VNTRs) block in different natural individuals of these two planthoppers. Comparison with a previously sequenced individual of SBPH revealed that the mitochondrial genetic variation within a species exists not only in the sequence and secondary structure of genes, but also in the gene order (the different location of trnH gene).
Conclusion
The mitochondrial genome arrangement pattern found in planthoppers was involved in rearrangements of both tRNA genes and protein-coding genes (PCGs). Different species from different genera of Delphacidae possessing the same mitochondrial gene rearrangement suggests that gene rearrangements of mitochondrial genome probably occurred before the differentiation of this family. After comparatively analyzing the gene order of different species of Hemiptera, we propose that except for some specific taxonomical group (e.g. the whiteflies) the gene order might have diversified in family level of this order. The VNTRs detected in the control region might provide additional genetic markers for studying population genetics, individual difference and phylogeographics of planthoppers.
doi:10.1186/1471-2164-14-417
PMCID: PMC3701526  PMID: 23799924
5.  Wolbachia-Host Interactions: Host Mating Patterns Affect Wolbachia Density Dynamics 
PLoS ONE  2013;8(6):e66373.
Wolbachia are maternally inherited intracellular bacteria that infect a wide range of arthropods and cause an array of effects on host reproduction, fitness and mating behavior. Although our understanding of the Wolbachia-associated effects on hosts is rapidly expanding, our knowledge of the host factors that mediate Wolbachia dynamics is rudimentary. Here, we explore the interactions between Wolbachia and its host, the two-spotted spider mite Tetranychus urticae Koch. Our results indicate that Wolbachia induces strong cytoplasmic incompatibility (CI), increases host fecundity, but has no effects on the longevity of females and the mating competitiveness of males in T. urticae. Most importantly, host mating pattern was found to affect Wolbachia density dynamics during host aging. Mating of an uninfected mite of either sex with an infected mite attenuates the Wolbachia density in the infected mite. According to the results of Wolbachia localization, this finding may be associated with the tropism of Wolbachia for the reproductive tissue in adult spider mites. Our findings describe a new interaction between Wolbachia and their hosts.
doi:10.1371/journal.pone.0066373
PMCID: PMC3688896  PMID: 23823081
6.  Recurrent giant orbital apocrine hidrocystoma 
Eye  2012;26(6):895-896.
doi:10.1038/eye.2012.57
PMCID: PMC3376301  PMID: 22498797
7.  WNT signaling underlies the pathogenesis of neuropathic pain in rodents 
The Journal of Clinical Investigation  2013;123(5):2268-2286.
Treating neuropathic pain is a major clinical challenge, and the underlying mechanisms of neuropathic pain remain elusive. We hypothesized that neuropathic pain–inducing nerve injury may elicit neuronal alterations that recapitulate events that occur during development. Here, we report that WNT signaling, which is important in developmental processes of the nervous system, plays a critical role in neuropathic pain after sciatic nerve injury and bone cancer in rodents. Nerve injury and bone cancer caused a rapid-onset and long-lasting expression of WNTs, as well as activation of WNT/frizzled/β-catenin signaling in the primary sensory neurons, the spinal dorsal horn neurons, and astrocytes. Spinal blockade of WNT signaling pathways inhibited the production and persistence of neuropathic pain and the accompanying neurochemical alterations without affecting normal pain sensitivity and locomotor activity. WNT signaling activation stimulated production of the proinflammatory cytokines IL-18 and TNF-α and regulated the NR2B glutamate receptor and Ca2+-dependent signals through the β-catenin pathway in the spinal cord. These findings indicate a critical mechanism underlying the pathogenesis of neuropathic pain and suggest that targeting the WNT signaling pathway may be an effective approach for treating neuropathic pain, including bone cancer pain.
doi:10.1172/JCI65364
PMCID: PMC3635721  PMID: 23585476
8.  Novel Method for Isolation of Murine Clara Cell Secretory Protein-Expressing Cells with Traces of Stemness 
PLoS ONE  2012;7(8):e43008.
Clara cells are non-ciliated, secretory bronchiolar epithelial cells that serve to detoxify harmful inhaled substances. Clara cells also function as stem/progenitor cells for repair in the bronchioles. Clara cell secretory protein (CCSP) is specifically expressed in pulmonary Clara cells and is widely used as a Clara cell marker. In addition CCSP promoter is commonly used to direct gene expression into the lung in transgenic models. The discovery of CCSP immunoreactivity in plasma membranes of airway lining cells prompted us to explore the possibility of enriching Clara cells by flow cytometry. We established a novel and simple method for the isolation of CCSP-expressing cell Clara cells using a combination of mechanical and enzymatic dissociation followed by flow cytometry sorting technology. We showed that ∼25% of dissociated cells from whole lung expressed CCSP. In the resulting preparation, up to 98% of cells expressed CCSP. Notably, we found that several common stem cell markers including CD44, CD133, Sca-1 and Sox2 were expressed in CCSP+ cells. Moreover, CCSP+ cells were able to form spheroid colonies in vitro with 0.97‰ efficiency. Parallel studies in vivo confirmed that a small population of CCSP−expressing cells in mouse airways also demonstrates stem cell-like properties such as label retention and harboring rare bronchioalveolar stem cells (BASCs) in terminal bronchioles (TBs). We conclude that CCSP+ cells exhibit a number of stem cell-like features including stem cell marker expression, bronchosphere colony formation and self-renewal ability. Clara cell isolation by flow cytometry sorting is a useful method for investigating the function of primary Clara cells in stem cell research and mouse models.
doi:10.1371/journal.pone.0043008
PMCID: PMC3420884  PMID: 22916196
9.  BinTree Seeking: A Novel Approach to Mine Both Bi-Sparse and Cohesive Modules in Protein Interaction Networks 
PLoS ONE  2011;6(11):e27646.
Modern science of networks has brought significant advances to our understanding of complex systems biology. As a representative model of systems biology, Protein Interaction Networks (PINs) are characterized by a remarkable modular structures, reflecting functional associations between their components. Many methods were proposed to capture cohesive modules so that there is a higher density of edges within modules than those across them. Recent studies reveal that cohesively interacting modules of proteins is not a universal organizing principle in PINs, which has opened up new avenues for revisiting functional modules in PINs. In this paper, functional clusters in PINs are found to be able to form unorthodox structures defined as bi-sparse module. In contrast to the traditional cohesive module, the nodes in the bi-sparse module are sparsely connected internally and densely connected with other bi-sparse or cohesive modules. We present a novel protocol called the BinTree Seeking (BTS) for mining both bi-sparse and cohesive modules in PINs based on Edge Density of Module (EDM) and matrix theory. BTS detects modules by depicting links and nodes rather than nodes alone and its derivation procedure is totally performed on adjacency matrix of networks. The number of modules in a PIN can be automatically determined in the proposed BTS approach. BTS is tested on three real PINs and the results demonstrate that functional modules in PINs are not dominantly cohesive but can be sparse. BTS software and the supporting information are available at: www.csbio.sjtu.edu.cn/bioinf/BTS/.
doi:10.1371/journal.pone.0027646
PMCID: PMC3225364  PMID: 22140454
10.  Preparation and immunogenicity of tag-free recombinant human eppin 
Asian Journal of Andrology  2011;13(6):889-894.
Human epididymal protease inhibitor (eppin) may be effective as a male contraceptive vaccine. In a number of studies, eppin with an engineered His6-tag has been produced using prokaryotic expression systems. For production of pharmaceutical-grade proteins for human use, however, the His6-tag must be removed. This study describes a method for producing recombinant human eppin without a His6-tag. We constructed plasmid pET28a (+)-His6-tobacco etch virus (TEV)-eppin for expression in Escherichia coli. After purification and refolding, the fusion protein His6-TEV-eppin was digested with TEV protease to remove the His6-tag and was further purified by NTA-Ni2+ affinity chromatography. Using this procedure, 2 mg of eppin without a His6-tag was isolated from 1 l of culture with a purity of >95%. The immunogenicity of the eppin was characterized using male Balb/c mice.
doi:10.1038/aja.2011.89
PMCID: PMC3739548  PMID: 21892195
Eppin; immunogenicity; male contraception; recombinant protein preparation; tag-free
11.  Calcium-Binding Protein Immunoreactivity Characterizes the Auditory System of Gekko gecko 
The Journal of comparative neurology  2010;518(17):3409-3426.
Geckos use vocalizations for intraspecific communication, but little is known about the organization of their central auditory system. We therefore used antibodies against the calcium-binding proteins calretinin (CR), parvalbumin (PV), and calbindin-D28k (CB) to characterize the gecko auditory system. We also examined expression of both glutamic acid decarboxlase (GAD) and synaptic vesicle protein (SV2). Western blots showed that these antibodies are specific to gecko brain. All three calcium-binding proteins were expressed in the auditory nerve, and CR immunoreactivity labeled the first-order nuclei and delineated the terminal fields associated with the ascending projections from the first-order auditory nuclei. PV expression characterized the superior olivary nuclei, whereas GAD immunoreactivity characterized many neurons in the nucleus of the lateral lemniscus and some neurons in the torus semicircularis. In the auditory midbrain, the distribution of CR, PV, and CB characterized divisions within the central nucleus of the torus semicircularis. All three calcium-binding proteins were expressed in nucleus medialis of the thalamus. These expression patterns are similar to those described for other vertebrates.
doi:10.1002/cne.22428
PMCID: PMC3170861  PMID: 20589907
cochlear nucleus; magnocellularis; laminaris; angularis; torus
12.  6-Benzyl-2-[(triphenyl-λ5-phosphanyl­idene)amino]-4,5,6,7-tetra­hydro­thieno[2,3-c]pyridine-3-carbonitrile 
In the title compound, C33H28N3PS, the P atom has a distorted tetra­hedral PNC3 environment, formed by the N atom and three aryl rings. No inter­molecular hydrogen-bonding inter­actions or π–π stacking inter­actions are present in the crystal structure.
doi:10.1107/S1600536811035082
PMCID: PMC3201343  PMID: 22058728
13.  ACS6, a Hydrogen sulfide-donating derivative of sildenafil, inhibits homocysteine-induced apoptosis by preservation of mitochondrial function 
Medical Gas Research  2011;1:20.
Background
The hydrogen sulfide-releasing sildenafil, ACS6, has been demonstrated to inhibit superoxide formation through donating hydrogen sulfide (H2S). We have found that H2S antagonizes homocysteine-induced oxidative stress and neurotoxicity. The aim of the present study is to explore the protection of ACS6 against homocysteine-triggered cytotoxicity and apoptosis and the molecular mechanisms underlying in PC12 cells.
Methods
Cell viability was determined by Cell Counting Kit-8 assay. Cell apoptosis was observed using the chromatin dye Hoechst 33258 and analyzed by Flow Cytometry after propidium iodide staining. Mitochondrial membrane potential was monitored using the fluorescent dye Rh123. Intracellular reactive oxygen species were determined by oxidative conversion of cell permeable 2',7'-dichlorfluorescein-diacetate to fluorescent 2',7'-dichlorfluorescein. The expression of cleaved caspase-3 and bcl-2 and the accumulation of cytosolic cytochrome c were analyzed by Western blot.
Results
We show that ACS6 protects PC12 cells against cytotoxicity and apoptosis induced by homocysteine and blocks homocysteine-triggered cytochrome c release and caspase-3 activation. ACS6 treatment results in not only prevention of homocysteine-caused mitochondrial membrane potential (Δψ) loss and reactive oxygen species (ROS) overproduction but also reversal of Bcl-2 down-expression.
Conclusions
These results indicate that ACS6 protects PC12 cells against homocysteine-induced cytotoxicity and apoptosis by preservation of mitochondrial function though inhibiting both loss of Δψ and accumulation of ROS as well as modulating the expression of Bcl-2. Our study provides evidence both for a neuroprotective effect of ACS6 and for further evaluation of ACS6 as novel neuroprotectants for Alzheimer's disease associated with homocysteine.
doi:10.1186/2045-9912-1-20
PMCID: PMC3231821  PMID: 22146536
H2S-releasing sildenafil; Apoptosis; Homocysteine; Mitochondrial membrane potential; Reactive oxygen species; Bcl-2
14.  7-Benzyl-3-(4-fluoro­phen­yl)-2-(pyrrol­idin-1-yl)-5,6,7,8-tetra­hydro­pyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4(3H)-one 
In the title compound, C26H25FN4OS, the thienopyrimidine fused-ring system is close to planar (r.m.s. deviation = 0.066 Å), with a maximum deviation of 0.1243 (17) Å for the N atom adjacent to the carbonyl group. This ring system forms dihedral angles of 67.5 (1) and 88.9 (1) ° with the adjacent six-membered rings. Inter­molecular C—H⋯O hydrogen bonding and C—H⋯π inter­actions help to stabilize the crystal structure.
doi:10.1107/S1600536811030625
PMCID: PMC3200784  PMID: 22065028
15.  SAX microscopy with fluorescent nanodiamond probes for high-resolution fluorescence imaging 
Biomedical Optics Express  2011;2(7):1946-1954.
We report the use of fluorescent nanodiamonds (FNDs) as a photostable fluorescent probe for high resolution saturated excitation (SAX) microscopy. We confirmed that FNDs show a nonlinear fluorescence response under saturated excitation conditions generated by intense excitation light. Using FNDs, we quantified the spatial resolution improvement inherent in SAX microscopy, and experimentally demonstrated the scalability of the spatial resolution of SAX microscopy. The photostability of the FNDs allowed us to perform nanoparticle imaging of a multicolor-stained macrophage cell with a spatial resolution beyond the diffraction limit.
doi:10.1364/BOE.2.001946
PMCID: PMC3130580  PMID: 21750771
(170.1790) Confocal microscopy; (170.2520) Fluorescence microscopy
16.  Transcription intermediary factor 1γ is a tumor suppressor in mouse and human chronic myelomonocytic leukemia 
The Journal of Clinical Investigation  2011;121(6):2361-2370.
Transcription intermediary factor 1γ (TIF1γ) was suggested to play a role in erythropoiesis. However, how TIF1γ regulates the development of different blood cell lineages and whether TIF1γ is involved in human hematological malignancies remain to be determined. Here we have shown that TIF1γ was a tumor suppressor in mouse and human chronic myelomonocytic leukemia (CMML). Loss of Tif1g in mouse HSCs favored the expansion of the granulo-monocytic progenitor compartment. Furthermore, Tif1g deletion induced the age-dependent appearance of a cell-autonomous myeloproliferative disorder in mice that recapitulated essential characteristics of human CMML. TIF1γ was almost undetectable in leukemic cells of 35% of CMML patients. This downregulation was related to the hypermethylation of CpG sequences and specific histone modifications in the gene promoter. A demethylating agent restored the normal epigenetic status of the TIF1G promoter in human cells, which correlated with a reestablishment of TIF1γ expression. Together, these results demonstrate that TIF1G is an epigenetically regulated tumor suppressor gene in hematopoietic cells and suggest that changes in TIF1γ expression may be a biomarker of response to demethylating agents in CMML.
doi:10.1172/JCI45213
PMCID: PMC3104753  PMID: 21537084
17.  Mining and Characterization of Sequence Tagged Microsatellites from the Brown Planthopper Nilaparvata lugens  
The brown planthopper, Nilaparvata lugens (Stål) (Hemiptera: Delphacidae), is an important pest of rice. To better understand the migration pattern and population structure of the Chinese populations of N. lugens, we developed and characterized 12 polymorphic microsatellites from the expressed sequence tags database of N. lugens. The occurrence of these simple sequence repeats was assessed in three populations collected from three provinces of China. The number of alleles per locus ranged from 3 to 13 with an average of 6.5 alleles per locus. The mean observed heterozygosity of the three populations ranged from 0.051 to 0.772 and the expected heterozygosity ranged from 0.074 to 0.766. The sequences of the 12 markers were highly variable. The polymorphism information content of the 12 markers was high and ranged from 0.074 to 0.807 (mean = 0.503). Sequencing of microsatellite alleles revealed that the fragment length differences were mainly due to the variation of the repeat motif. Significant genetic differentiation was detected among the three N. lugens populations as the Fst ranged from 0.034 to 0.273. Principle coordinates analysis also revealed significant genetic differentiation between populations of different years. We conclude that these microsatellite markers will be a powerful tools to study the migration routine of the N. lugens.
doi:10.1673/031.011.13401
PMCID: PMC3281394  PMID: 22243416
migration routine; expressed sequences; population genetics
18.  DFNB44, a Novel Autosomal Recessive Non-Syndromic Hearing Impairment Locus, Maps to Chromosome 7p14.1-q11.22 
Human heredity  2004;57(4):195-199.
The genetic etiology for many forms of hearing impairment (HI) is very diverse. Non-syndromic HI (NSHI) is one of the most heterogeneous traits known. Autosomal recessive forms of prelingual HI account for ∼75% of hereditary cases. A novel autosomal recessive NSHI locus, DFNB44, was mapped to a 20.9 cM genetic interval on chromosome 7p14.1-q11.22, according to the Marshfield genetic map, in a consanguineous Pakistani family. Multipoint linkage analysis resulted in a maximum LOD score of 5.0 at marker D7S1818. The 3-unit support interval ranged from marker D7S2209 to marker D7S2435, spanning a 30.1 Mb region on the sequence-based physical map.
doi:10.1159/000081446
PMCID: PMC2920138  PMID: 15583425
7p14.1-q11.22; DFNB44; Non-syndromic hearing impairment; Pakistan
19.  SimPed: A Simulation Program to Generate Haplotype and Genotype Data for Pedigree Structures 
Human heredity  2005;60(2):119-122.
With the widespread availability of SNP genotype data, there is great interest in analyzing pedigree haplotype data. Intermarker linkage disequilibrium for micro-satellite markers is usually low due to their physical distance; however, for dense maps of SNP markers, there can be strong linkage disequilibrium between marker loci. Linkage analysis (parametric and nonparametric) and family-based association studies are currently being carried out using dense maps of SNP marker loci. Monte Carlo methods are often used for both linkage and association studies; however, to date there are no programs available which can generate haplotype and/or genotype data consisting of a large number of loci for pedigree structures. SimPed is a program that quickly generates haplotype and/or genotype data for pedigrees of virtually any size and complexity. Marker data either in linkage disequilibrium or equilibrium can be generated for greater than 20,000 diallelic or multiallelic marker loci. Haplotypes and/or genotypes are generated for pedigree structures using specified genetic map distances and haplotype and/or allele frequencies. The simulated data generated by SimPed is useful for a variety of purposes, including evaluating methods that estimate haplotype frequencies for pedigree data, evaluating type I error due to intermarker linkage disequilibrium and estimating empirical p values for linkage and family-based association studies.
doi:10.1159/000088914
PMCID: PMC2909095  PMID: 16224189
Simulation; Pedigree structure; Type I error; Empirical p values
20.  A Novel Autosomal Recessive Nonsyndromic Hearing Impairment Locus (DFNB42) Maps to Chromosome 3q13.31-q22.3 
A consanguineous family with autosomal recessive nonsyndromic hearing impairment (NSHI) was ascertained in Pakistan and displayed significant evidence of linkage to 3q13.31-q22.3. The novel locus (DFNB42) segregating in this kindred, maps to a 21.6 cM region according to a genetic map constructed using data from both the deCode and Marshfield genetic maps. This region of homozygosity is flanked by markers D3S1278 and D3S2453. A maximum multipoint LOD score of 3.72 was obtained at marker D3S4523. DFNB42 represents the third autosomal recessive NSHI locus to map to chromosome 3.
doi:10.1002/ajmg.a.30508
PMCID: PMC2909096  PMID: 15641023
3q13.31-q22.3; DFNB42; nonsyndromic hearing impairment; Pakistan
21.  Novel Sequence Variants in the TMC1 Gene in Pakistani Families With Autosomal Recessive Hearing Impairment 
Human mutation  2005;26(4):396.
Though many hearing impairment genes have been identified, only a few of these genes have been screened in population studies. For this study, 168 Pakistani families with autosomal recessive hearing impairment not due to mutations in the GJB2 (Cx26) gene underwent a genome scan. Two-point and multipoint parametric linkage analyses were carried out. Twelve families had two-point or multipoint LOD scores of 1.4 or greater within the transmembrane cochlear expressed gene 1 (TMC1) region and were subjected to further screening with direct DNA sequencing. Five novel putatively functional non-synonymous sequence variants, c.830A>G (p.Y277C), c.1114G>A (p.V372M), c.1334G>A (p.R445H), c.2004T>G (p.S668R) and c.2035G>A (p.E679K), were found to segregate within seven families, but were not observed in 234 Pakistani control chromosomes. The variants c.830A>G (p.Y277C), c.1114G>A (p.V372M) and c.1334G>A (p.R445H) occurred at highly conserved regions and were predicted to lie within hydrophobic transmembrane domains, while non-synonymous variants c.2004T>G (p.S668R) and c.2035G>A (p.E679K) occurred in extracellular regions that were not highly conserved. There is evidence that the c.2004T>G (p.S668R) variant may have occurred at a phosphorylation site. One family has the known splice site mutation c.536 -8T>A. The prevalence of non-syndromic hearing impairment due to TMC1 in this Pakistani population is 4.4% (95%CI: 1.9, 8.6%). The TMC1 protein might have an important function in K+ channels of inner hair cells, which would be consistent with the hypothetical structure of protein domains in which sequence variants were identified.
doi:10.1002/humu.9374
PMCID: PMC2909098  PMID: 16134132
TMC1; autosomal recessive non-syndromic hearing impairment; Pakistan; prevalence
22.  Mapping of a Novel Autosomal Recessive Nonsyndromic Deafness Locus (DFNB46) to Chromosome 18p11.32-p11.31 
Hereditary nonsyndromic deafness (NSD) is extremely heterogeneous. Autosomal recessive (AR) forms account for ~75% of genetic cases. To date, over 40 ARNSD loci have been mapped. A novel locus (DFNB46) for ARNSD was mapped to chromosome 18p11.32-p11.31 in a five-generation Pakistani family. A 10 cM genome-wide scan and fine mapping was carried out using microsatellite markers. A maximum multipoint LOD score of 3.8 was obtained at two markers, D18S481 and D18S1370. The three-unit support interval is flanked by markers D18S59 and D18S391, corresponds to a 17.6 cM region according to the decode genetic map and spans 5.8 Mb on the sequence-based physical map.
doi:10.1002/ajmg.a.30516
PMCID: PMC2909100  PMID: 15637723
18p11.32-p11.31; DFNB19; DFNB46; nonsyndromic deafness; Pakistan
23.  DFNB39, a recessive form of sensorineural hearing impairment, maps to chromosome 7q11.22–q21.12 
This article describes the identification of a novel locus (DFNB39) responsible for an autosomal recessive form of hearing loss segregating in a Pakistani consanguineous family. The hearing impaired members of this family present with profound prelingual sensorineural hearing impairment and use sign language for communications. Linkage was established to microsatellite markers located on chromosome 7q with a maximum multipoint lod score of 3.8. The region of homozygosity spans a 19 cM region that is bounded by markers D7S3046 and D7S644.
doi:10.1038/sj.ejhg.5201041
PMCID: PMC2909101  PMID: 14512973
autosomal recessive nonsyndromic hearing impairment; DFNB39; linkage mapping; Pakistan; 7q11.22—q21.12
24.  A novel autosomal recessive non-syndromic hearing impairment locus (DFNB47) maps to chromosome 2p25.1-p24.3 
Human genetics  2005;118(5):605-610.
Hereditary hearing impairment (HI) displays extensive genetic heterogeneity. Autosomal recessive (AR) forms of prelingual HI account for ~75% of cases with a genetic etiology. A novel AR non-syndromic HI locus (DFNB47) was mapped to chromosome 2p25.1-p24.3, in two distantly related Pakistani kindreds. Genome scan and fine mapping were carried out using microsatellite markers. Multipoint linkage analysis resulted in a maximum LOD score of 4.7 at markers D2S1400 and D2S262. The three-unit support interval was bounded by D2S330 and D2S131. The region of homozygosity was found within the three-unit support interval and flanked by markers D2S2952 and D2S131, which corresponds to 13.2 cM according to the Rutgers combined linkage-physical map. This region contains 5.3 Mb according to the sequence-based physical map. Three candidate genes, KCNF1, ID2 and ATP6V1C2 were sequenced, and were found to be negative for functional sequence variants.
doi:10.1007/s00439-005-0079-8
PMCID: PMC2909103  PMID: 16261342
25.  Localization of A Novel Autosomal Recessive Non-Syndromic Hearing Impairment Locus (DFNB38) to 6q26–q27 in a Consanguineous Kindred from Pakistan 
Human heredity  2003;55(1):71-74.
For autosomal recessive nonsyndromic hearing impairment over 30 loci have been mapped and 19 genes have been identified. DFNB38, a novel locus for autosomal recessive nonsyndromic hearing impairment, was localized in a consanguineous Pakistani kindred to 6q26–q27. The affected family members present with profound prelingual sensorineural hearing impairment and use sign language for communications. Linkage was established to microsatellite markers located on chromosome 6q26–q27 (Multipoint lod score 3.6). The genetic region for DFNB38 spans 10.1 cM according to the Marshfield genetic map and is bounded by markers D6S980 and D6S1719. This genetic region corresponds to 3.4 MB on the sequence-based physical map.
doi:10.1159/000071813
PMCID: PMC2909108  PMID: 12890929
Autosomal recessive hearing impairment; DFNB38; Gene mapping; Pakistan; 6q26–q27

Results 1-25 (35)