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1.  Unexplained False Negative Results in Noninvasive Prenatal Testing: Two Cases Involving Trisomies 13 and 18 
Case Reports in Genetics  2015;2015:926545.
Noninvasive prenatal testing (NIPT) validation studies show high sensitivity and specificity for detection of trisomies 13, 18, and 21. False negative cases have rarely been reported. We describe a false negative case of trisomy 13 and another of trisomy 18 in which NIPT was commercially marketed directly to the clinician. Both cases came to our attention because a fetal anatomy scan at 20 weeks of gestation revealed multiple anomalies. Karyotyping of cultured amniocytes showed nonmosaic trisomies 13 and 18, respectively. Cytogenetic investigation of cytotrophoblast cells from multiple placental biopsies showed a low proportion of nontrisomic cells in each case, but this was considered too small for explaining the false negative NIPT result. The discordant results also could not be explained by early gestational age, elevated maternal weight, a vanishing twin, or suboptimal storage or transport of samples. The root cause of the discrepancies could, therefore, not be identified. The couples involved experienced difficulties in accepting the unexpected and late-adverse outcome of their pregnancy. We recommend that all parties involved in caring for couples who choose NIPT should collaborate to clarify false negative results in order to unravel possible biological causes and to improve the process of patient care from initial counseling to communication of the result.
doi:10.1155/2015/926545
PMCID: PMC4475527  PMID: 26137330
2.  3p14 De Novo Interstitial Microdeletion in a Patient with Intellectual Disability and Autistic Features with Language Impairment: A Comparison with Similar Cases 
Case Reports in Genetics  2015;2015:876348.
To date, few cases of 3p proximal interstitial deletions have been reported and the phenotype and genotype correlation is not well understood. Here, we report a new case of a 3p proximal interstitial deletion. The patient is an 11-year-old female with speech and social interaction difficulties, learning disability, and slight facial dysmorphism, but no other major malformations. An 8 Mb de novo interstitial deletion at 3p14.2-p14.1, from position 60.461.316 to 68.515.453, was revealed by means of array comparative genomic hybridization and confirmed using quantitative reverse-transcription polymerase chain reaction assays. This region includes six genes: FEZF2, CADPS, SYNPR, ATXN7, PRICKLE, and MAGI1, that are known to have a role in neurodevelopment. These genes are located on the proximal side of the deletion. We compare our case with previously well-defined patients reported in the literature and databases.
doi:10.1155/2015/876348
PMCID: PMC4446465  PMID: 26075115
3.  PWS/AS MS-MLPA Confirms Maternal Origin of 15q11.2 Microduplication 
Case Reports in Genetics  2015;2015:474097.
The proximal region of the long arm of chromosome 15q11.2-q13 is associated with various neurodevelopmental disorders, including Prader-Willi (PWS) and Angelman (AS) syndromes, autism, and other developmental abnormalities resulting from deletions and duplications. In addition, this region encompasses imprinted genes that cause PWS or AS, depending on the parent-of-origin. This imprinting allows for diagnosis of PWS or AS based on methylation status using methylation sensitive (MS) multiplex ligation dependent probe amplification (MLPA). Maternally derived microduplications at 15q11.2-q13 have been associated with autism and other neuropsychiatric disorders. Multiple methods have been used to determine the parent-of-origin for 15q11.2-q13 microdeletions and microduplications. In the present study, a four-year-old nondysmorphic female patient with developmental delay was found to have a de novo ~5 Mb duplication within 15q11.2 by oligonucleotide genomic array. In order to determine the significance of this microduplication to the clinical phenotype, the parent-of-origin needed to be identified. The PWS/AS MS-MLPA assay is generally used to distinguish between deletion and uniparental disomy (UPD) of 15q11.2-q13, resulting in either PWS or AS. However, our study shows that PWS/AS MS-MLPA can also efficiently distinguish the parental origin of duplications of 15q11.2-q13.
doi:10.1155/2015/474097
PMCID: PMC4439467  PMID: 26064710
4.  Identification of Novel Mutations in Spatacsin and Apolipoprotein B Genes in a Patient with Spastic Paraplegia and Hypobetalipoproteinemia 
Case Reports in Genetics  2015;2015:219691.
Complicated hereditary spastic paraplegia (HSP) presents with complex neurological and nonneurological manifestations. We report a patient with autosomal recessive (AR) HSP in whom laboratory investigations revealed hypobetalipoproteinemia raising the possibility of a shared pathophysiology of these clinical features. A lipid profile of his parents disclosed a normal maternal lipid profile. However, the paternal lipid profile was similar to that of the patient suggesting autosomal dominant transmission of this trait. Whole exome sequence analysis was performed and novel mutations were detected in both the SPG11 and the APOB genes. Genetic testing of the parents showed that both APOB variants were inherited from the father while the SPG11 variants were inherited one from each parent. Our results indicate that, in this patient, the hypobetalipoproteinemia and spastic paraplegia are unrelated resulting from mutations in two independent genes. This clinical study provides support for the use of whole exome sequencing as a diagnostic tool for identification of mutations in conditions with complex presentations.
doi:10.1155/2015/219691
PMCID: PMC4439468  PMID: 26064709
5.  Identification of SLC22A5 Gene Mutation in a Family with Carnitine Uptake Defect 
Case Reports in Genetics  2015;2015:259627.
Primary systemic carnitine deficiency is caused by homozygous or compound heterozygous mutation in the SLC22A5 gene on chromosome 5q31. The most common presentations are in infancy and early childhood with either metabolic decompensation or cardiac and myopathic manifestations. We report a case of 9-year-old boy with dysmorphic appearance and hypertrophic cardiomyopathy. Tandem MS spectrometry analysis was compatible with carnitine uptake defect (CUD). His sister had died due to sudden infant death at 19 months. His second 4-year-old sister's echocardiographic examination revealed hypertrophic cardiomyopathy, also suffering from easy fatigability. Her tandem MS spectrometry analyses resulted in CUD. We sequenced all the exons of the SLC22A5 gene encoding the high affinity carnitine transporter OCTN2 in the DNA. And one new mutation (c.1427T>G → p.Leu476Arg) was found in the boy and his sister in homozygous form, leading to the synthesis of an altered protein which causes CUD. The parent's molecular diagnosis supported the carrier status. In order to explore the genetic background of the patient's dysmorphic appearance, an array-CGH analysis was performed that revealed nine copy number variations only. Here we report a novel SLC22A5 mutation with the novel hallmark of its association with dysmorphologic feature.
doi:10.1155/2015/259627
PMCID: PMC4436458  PMID: 26075114
6.  Cognitive, Affective Problems and Renal Cross Ectopy in a Patient with 48,XXYY/47,XYY Syndrome 
Case Reports in Genetics  2015;2015:950574.
Klinefelter syndrome is the most common sex chromosome abnormality (SCA) in infertile patients and 47,XXY genomic configuration constitutes most of the cases. However, additional Xs and/or Y such as 48,XXYY, 48,XXXY, and 47,XYY can occur less frequently than 47,XXY. Those configurations were considered as variants of Klinefelter syndrome. In this report, we present an infertile man with tall stature and decreased testicular volume. Semen analysis and hormonal evaluation supported the diagnosis of nonobstructive azoospermia. Genetic investigation demonstrated an abnormal male karyotype with two X chromosomes and two Y chromosomes consistent with 48,XXYY(17)/47,XYY (13). Additionally, the patient expressed cognitive and affective problems which were documented by psychomotor retardation and borderline intelligence measured by an IQ value between 70 and 80. Systemic evaluation also revealed cross ectopy and malrotation of the right kidney in the patient. The couple was referred to microtesticular sperm extraction (micro-TESE)/intracytoplasmic sperm injection (ICSI) cycles and preimplantation genetic diagnosis (PGD). To the best of our knowledge, this is the first report of combination of XYY and XXYY syndromes associated with cognitive, affective dysfunction and renal malrotation.
doi:10.1155/2015/950574
PMCID: PMC4436470  PMID: 26075116
7.  Deletion of 7q33-q35 in a Patient with Intellectual Disability and Dysmorphic Features: Further Characterization of 7q Interstitial Deletion Syndrome 
Case Reports in Genetics  2015;2015:131852.
This case report concerns a 16-year-old girl with a 9.92 Mb, heterozygous interstitial chromosome deletion at 7q33-q35, identified using array comparative genomic hybridization. The patient has dysmorphic facial features, intellectual disability, recurrent infections, self-injurious behavior, obesity, and recent onset of hemihypertrophy. This patient has overlapping features with previously reported individuals who have similar deletions spanning the 7q32-q36 region. It has been difficult to describe an interstitial 7q deletion syndrome due to variations in the sizes and regions in the few patients reported in the literature. This case contributes to the further characterization of an interstitial distal 7q deletion syndrome.
doi:10.1155/2015/131852
PMCID: PMC4433680  PMID: 26064708
8.  Ellis-van Creveld Syndrome: Mutations Uncovered in Lebanese Families 
Case Reports in Genetics  2015;2015:528481.
Background. Ellis-van Creveld (EvC) syndrome is a rare, autosomal recessive disorder characterized by short stature, short limbs, growth retardation, polydactyly, and ectodermal defects with cardiac anomalies occurring in around 60% of cases. EVC syndrome has been linked to mutations in EVC and EVC2 genes. Case Presentation. We report EvC syndrome in two unrelated Lebanese families both having homozygous mutations in the EVC2 gene, c.2653C>T (p.(Arg885*)) and c.2012_2015del (p.(Leu671*)) in exons 15 and 13, respectively, with the latter being reported for the first time. Conclusion. Although EvC has been largely described in the medical literature, clinical features of this syndrome vary. While more research is required to explore other genes involved in EvC, early diagnosis and therapeutic care are important to achieve a better quality of life.
doi:10.1155/2015/528481
PMCID: PMC4430639  PMID: 26064711
9.  Incidental Finding of a Homozygous p.M348K Asymptomatic Italian Patient Confirms the Many Faces of Cystic Fibrosis 
Case Reports in Genetics  2015;2015:289627.
Cystic fibrosis (CF; OMIM number 219700) is an autosomal recessive disease caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene, which results in abnormal viscous mucoid secretions in multiple organs and whose main clinical features are pancreatic insufficiency, chronic endobronchial infection, and male infertility. We report the case of a 47-year-old apparently normal male resulting in homozygosity for the mutation p.M348K from nonconsanguineous parents. The proband was screened using a standard panel of 70 different tested on NanoChip 400 platform. The massive parallel pyrosequencing on 454 JS machine allowed the second level analysis. The patient was firstly screened with two different platforms available in our laboratory, obtaining an ambiguous signal for the p.R347P mutation. For this reason we decided to clarify the discordant result of CFTR status by Next Generation Sequencing (NGS) using 454 Junior instrument. The patient is resulted no carrier of the p.R347P mutation, but NGS highlighted a homozygous substitution from T>A at position 1043 in the coding region, causing an amino acid substitution from methionine to lysine (p.M348K). Casual finding of p.M348K homozygote mutation in an individual, without any feature of classical or nonclassical CF form, allowed us to confirm that p.M348K is a benign rare polymorphism.
doi:10.1155/2015/289627
PMCID: PMC4397493  PMID: 25922769
10.  Case of 7p22.1 Microduplication Detected by Whole Genome Microarray (REVEAL) in Workup of Child Diagnosed with Autism 
Case Reports in Genetics  2015;2015:212436.
Introduction. More than 60 cases of 7p22 duplications and deletions have been reported with over 16 of them occurring without concomitant chromosomal abnormalities. Patient and Methods. We report a 29-month-old male diagnosed with autism. Whole genome chromosome SNP microarray (REVEAL) demonstrated a 1.3 Mb interstitial duplication of 7p22.1 ->p22.1 arr 7p22.1 (5,436,367–6,762,394), the second smallest interstitial 7p duplication reported to date. This interval included 14 OMIM annotated genes (FBXL18, ACTB, FSCN1, RNF216, OCM, EIF2AK1, AIMP2, PMS2, CYTH3, RAC1, DAGLB, KDELR2, GRID2IP, and ZNF12). Results. Our patient presented features similar to previously reported cases with 7p22 duplication, including brachycephaly, prominent ears, cryptorchidism, speech delay, poor eye contact, and outburst of aggressive behavior with autism-like features. Among the genes located in the duplicated segment, ACTB gene has been proposed as a candidate gene for the alteration of craniofacial development. Overexpression of RNF216L has been linked to autism. FSCN1 may play a role in neurodevelopmental disease. Conclusion. Characterization of a possible 7p22.1 Duplication Syndrome has yet to be made. Recognition of the clinical spectrum in patients with a smaller duplication of 7p should prove valuable for determining the minimal critical region, helping delineate a better prediction of outcome and genetic counseling
doi:10.1155/2015/212436
PMCID: PMC4393924  PMID: 25893121
11.  Rare Manifestation of a c.290 C>T, p.Gly97Glu VCP Mutation 
Case Reports in Genetics  2015;2015:239167.
Introduction. The valosin-containing protein (VCP) regulates several distinct cellular processes. Consistent with this, VCP mutations manifest variable clinical phenotypes among and within families and are a diagnostic challenge. Methods. A 60-year-old man who played ice hockey into his 50's was evaluated by electrodiagnostics, muscle biopsy, and molecular genetics. Results. With long-standing pes cavus and toe walking, our patient developed progressive weakness, cramps, memory loss, and paresthesias at age 52. An axonal sensorimotor neuropathy was found upon repeated testing at age 58. Neuropathic histopathology was present in the quadriceps, and exome sequencing revealed the VCP mutation c.290 C>T, p.Gly97Glu. Conclusions. Our patient reflects the clinical heterogeneity of VCP mutations, as his neurological localization is a spectrum between a lower motor neuron disorder and a hereditary axonal peripheral neuropathy such as CMT2. Our case demonstrates a rare manifestation of the c.290 C>T, pGly97Glu VCP mutation.
doi:10.1155/2015/239167
PMCID: PMC4386706  PMID: 25878907
12.  A Novel PHEX Mutation in Japanese Patients with X-Linked Hypophosphatemic Rickets 
Case Reports in Genetics  2015;2015:301264.
X-linked hypophosphatemic rickets (XLH) is a dominant inherited disorder characterized by renal phosphate wasting, aberrant vitamin D metabolism, and abnormal bone mineralization. Inactivating mutations in the gene encoding phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) have been found to be associated with XLH. Here, we report a 16-year-old female patient affected by hypophosphatemic rickets. We evaluated her serum fibroblast growth factor 23 (FGF23) levels and conducted sequence analysis of the disease-associated genes of FGF23-related hypophosphatemic rickets: PHEX, FGF23, dentin matrix protein 1, and ectonucleotide pyrophosphatase/phosphodiesterase 1. She was diagnosed with XLH based on her clinical features and family history. Additionally, we observed elevated FGF23 levels and a novel PHEX exon 9 mutation (c.947G>T; p.Gly316Val) inherited from her father. Although bioinformatics showed that the mutation was neutral, Gly316 is perfectly conserved among humans, mice, and rats, and there were no mutations in other FGF23-related rickets genes, suggesting that in silico analysis is limited in determining mutation pathogenicity. In summary, we present a female patient and her father with XLH harboring a novel PHEX mutation that appears to be causative of disease. Measurement of FGF23 for hypophosphatemic patients is therefore useful for the diagnosis of FGF23-dependent hypophosphatemia.
doi:10.1155/2015/301264
PMCID: PMC4377384  PMID: 25861491
14.  Unusual Presentation of Pelizaeus-Merzbacher Disease: Female Patient with Deletion of the Proteolipid Protein 1 Gene 
Case Reports in Genetics  2015;2015:453105.
Pelizaeus-Merzbacher disease (PMD) is neurodegenerative leukodystrophy caused by dysfunction of the proteolipid protein 1 (PLP1) gene on Xq22, which codes for an essential myelin protein. As an X-linked condition, PMD primarily affects males; however there have been a small number of affected females reported in the medical literature with a variety of different mutations in this gene. No affected females to date have a deletion like our patient. In addition to this, our patient has skewed X chromosome inactivation which adds to her presentation as her unaffected mother also carries the mutation.
doi:10.1155/2015/453105
PMCID: PMC4348602  PMID: 25789183
15.  Novel Mutation in a Patient with Cholesterol Ester Storage Disease 
Case Reports in Genetics  2015;2015:347342.
Cholesterol ester storage disease (CESD) is a chronic liver disease that typically presents with hepatomegaly. It is characterized by hypercholesterolemia, hypertriglyceridemia, high-density lipoprotein deficiency, and abnormal lipid deposition within multiple organs. It is an autosomal recessive disease that is due to a deficiency in lysosomal acid lipase (LAL) activity, which is coded by the lysosomal acid lipase gene (LIPA). We describe the case of a 5-year-old south Asian female incidentally found to have hepatomegaly, and subsequent workup confirmed the diagnosis of CESD. DNA sequencing confirmed the presence of a novel hepatic mutation. It is a four-nucleotide deletion c.57_60delTGAG in exon 2 of the LIPA gene. This mutation is predicted to result in a premature translation stop downstream of the deletion (p.E20fs) and, therefore, is felt to be a disease-causing mutation.
doi:10.1155/2015/347342
PMCID: PMC4334435  PMID: 25722898
16.  A Prenatally Ascertained De Novo Terminal Deletion of Chromosomal Bands 1q43q44 Associated with Multiple Congenital Abnormalities in a Female Fetus 
Case Reports in Genetics  2015;2015:517678.
Terminal deletions in the long arm of chromosome 1 result in a postnatally recognizable disorder described as 1q43q44 deletion syndrome. The size of the deletions and the resulting phenotype varies among patients. However, some features are common among patients as the chromosomal regions included in the deletions. In the present case, ultrasonography at 22 weeks of gestation revealed choroid plexus cysts (CPCs) and a single umbilical artery (SUA) and therefore amniocentesis was performed. Chromosomal analysis revealed a possible terminal deletion in 1q and high resolution array CGH confirmed the terminal 1q43q44 deletion and estimated the size to be approximately 8 Mb. Following termination of pregnancy, performance of fetopsy allowed further clinical characterization. We report here a prenatal case with the smallest pure terminal 1q43q44 deletion, that has been molecularly and phenotypically characterized. In addition, to our knowledge this is the first prenatal case reported with 1q13q44 terminal deletion and Pierre-Robin sequence (PRS). Our findings combined with review data from the literature show the complexity of the genetic basis of the associated syndrome.
doi:10.1155/2015/517678
PMCID: PMC4334433  PMID: 25722899
17.  Exceptional Complex Chromosomal Rearrangements in Three Generations 
Case Reports in Genetics  2015;2015:321014.
We report an exceptional complex chromosomal rearrangement (CCR) found in three individuals in a family that involves 4 chromosomes with 5 breakpoints. The CCR was ascertained in a phenotypically abnormal newborn with additional chromosomal material on the short arm of chromosome 4. Maternal karyotyping indicated that the mother carried an apparently balanced CCR involving chromosomes 4, 6, 11, and 18. Maternal transmission of the derivative chromosome 4 resulted in partial trisomy for chromosomes 6q and 18q and a partial monosomy of chromosome 4p in the proband. Further family studies found that the maternal grandmother carried the same apparently balanced CCR as the proband's mother, which was confirmed using the whole chromosome painting (WCP) FISH. High resolution whole genome microarray analysis of DNA from the proband's mother found no evidence for copy number imbalance in the vicinity of the CCR translocation breakpoints, or elsewhere in the genome, providing evidence that the mother's and grandmother's CCRs were balanced at a molecular level. This structural rearrangement can be categorized as an exceptional CCR due to its complexity and is a rare example of an exceptional CCR being transmitted in balanced and/or unbalanced form across three generations.
doi:10.1155/2015/321014
PMCID: PMC4333187  PMID: 25722897
18.  Severe Psychomotor Delay in a Severe Presentation of Cat-Eye Syndrome 
Case Reports in Genetics  2015;2015:943905.
Cat-eye syndrome is a rare genetic syndrome of chromosomal origin. Individuals with cat-eye syndrome are characterized by the presence of preauricular pits and/or tags, anal atresia, and iris coloboma. Many reported cases also presented with variable congenital anomalies and intellectual disability. Most patients diagnosed with CES carry a small supernumerary bisatellited marker chromosome, resulting in partial tetrasomy of 22p-22q11.21. There are two types of small supernumerary marker chromosome, depending on the breakpoint site. In a very small proportion of cases, other cytogenetic anomalies are reportedly associated with the cat-eye syndrome phenotype. Here, we report a patient with cat-eye syndrome caused by a type 1 small supernumerary marker chromosome. The phenotype was atypical and included a severe developmental delay. The use of array comparative genomic hybridization ruled out the involvement of another chromosomal imbalance in the neurological phenotype. In the literature, only a few patients with cat-eye syndrome present with a severe developmental delay, and all of the latter carried an atypical partial trisomy 22 or an uncharacterized small supernumerary marker chromosome. Hence, this is the first report of a severe neurological phenotype in cat-eye syndrome with a typical type 1 small supernumerary marker chromosome. Our observation clearly complicates prognostic assessment, particularly when cat-eye syndrome is diagnosed prenatally.
doi:10.1155/2015/943905
PMCID: PMC4310452  PMID: 25648072
19.  A New Case of 13q12.2q13.1 Microdeletion Syndrome Contributes to Phenotype Delineation 
Case Reports in Genetics  2014;2014:470830.
A recently described genetic disorder has been associated with 13q12.3 microdeletion spanning three genes, namely, KATNAL1, LINC00426, and HMGB1. Here, we report a new case with similar clinical features that we have followed from birth to 5 years old. The child carried a complex rearrangement with a double translocation: 46,XX,t(7;13)(p15;q14),t(11;15)(q23;q22). Array-CGH identified a de novo microdeletion at 13q12.2q13.1 spanning 3–3.4 Mb and overlapping 13q12.3 critical region. Clinical features resembling those reported in the literature confirm the existence of a distinct 13q12.3 microdeletion syndrome and provide further evidence that is useful to characterize its phenotypic expression during the 5 years of development.
doi:10.1155/2014/470830
PMCID: PMC4259072  PMID: 25506442
20.  Partial Gene Deletions of PMP22 Causing Hereditary Neuropathy with Liability to Pressure Palsies 
Case Reports in Genetics  2014;2014:946010.
Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal neuropathy that is commonly caused by a reciprocal 1.5 Mb deletion on chromosome 17p11.2, at the site of the peripheral myelin protein 22 (PMP22) gene. Other patients with similar phenotypes have been shown to harbor point mutations or small deletions, although there is some clinical variation across these patients. In this report, we describe a case of HNPP with copy number changes in exon or promoter regions of PMP22. Multiplex ligation-dependent probe analysis revealed an exon 1b deletion in the patient, who had been diagnosed with HNPP in the first decade of life using molecular analysis.
doi:10.1155/2014/946010
PMCID: PMC4258352  PMID: 25506001
21.  A Case of Acute Myeloid Leukemia with a Previously Unreported Translocation (14; 15) (q32; q13) 
Case Reports in Genetics  2014;2014:921240.
Background. We hereby describe what we believe to be the first reported case of t (14; 15) (q32; q13) associated with acute myeloid leukemia (AML). Methods. PubMed, Embase, and OVID search engines were used to review the related literature and similar published cases. Case. A47-year-old female presented in December 2011 with AML (acute myelomonocytic leukemia) with normal cytogenetics; molecular testing revealed FLT-3 internal tandem duplication (ITD) mutation, while no mutations involving FLT3 D385/I836, NPM1 exon 12, or KIT exons 8 and 17 were detected. She was induced with 7 + 3 (cytarabine + idarubicin) and achieved complete remission after a second induction with high-dose cytarabine (HiDAC) followed by uneventful consolidation. She presented 19 months after diagnosis with relapsed disease. Of note, at relapse cytogenetic analysis revealed t (14; 15) (q32; q13), while FLT-3 analysis showed a codon D835 mutation (no ITD mutation was detected). She proved refractory to the initial clofarabine-based regimen, so FLAG-idarubicin then was used. She continued to have persistent disease, and she was discharged on best supportive care. Conclusion. Based on this single case of AML with t (14; 15) (q32; q13), this newly reported translocation may be associated with refractory disease.
doi:10.1155/2014/921240
PMCID: PMC4243475  PMID: 25436161
22.  Atypical Association of Angelman Syndrome and Klinefelter Syndrome in a Boy with 47,XXY Karyotype and Deletion 15q11.2-q13 
Case Reports in Genetics  2014;2014:517091.
Angelman syndrome (AS, OMIM 105830) is a neurogenetic disorder with firm clinical diagnostic guidelines, characterized by severe developmental delay and speech impairment, balanced and behavioral disturbance as well as microcephaly, seizures, and a characteristic electroencephalogram (EEG). The majority of AS cases (70%) are caused by a 15q11.2-q13 deletion on the maternally derived chromosome. The frequency of AS has been estimated to be between 1/10000 and 1/20000. Klinefelter syndrome (KS) occurs due to the presence of an extra X chromosome (karyotype 47,XXY). The main features in KS are small testes, hypergonadotropic hypogonadism, gynecomastia, learning difficulties, and infertility. We present what is, to our knowledge, the first case of a patient with both KS and AS due to a 15q11.2-q13 deletion on the maternally derived chromosome and an extra X chromosome of paternal origin. He showed dysmorphic features, axial hypotonia, and delayed acquisition of motor skills. Early diagnosis is essential for optimal treatment of AS children; this is one of the earliest diagnosed cases of AS probably due to the presence of two syndromes. Clinical findings in this patient here described may be helpful to identify any other cases and to evaluate recurrence risks in these families.
doi:10.1155/2014/517091
PMCID: PMC4212645  PMID: 25379297
23.  Alsin Related Disorders: Literature Review and Case Study with Novel Mutations 
Case Reports in Genetics  2014;2014:691515.
Mutations in the ALS2 gene cause three distinct disorders: infantile ascending hereditary spastic paraplegia, juvenile primary lateral sclerosis, and autosomal recessive juvenile amyotrophic lateral sclerosis. We present a review of the literature and the case of a 16-year-old boy who is, to the best of our knowledge, the first Portuguese case with infantile ascending hereditary spastic paraplegia. Clinical investigations included sequencing analysis of the ALS2 gene, which revealed a heterozygous mutation in exon 5 (c.1425_1428del p.G477Afs*19) and a heterozygous and previously unreported variant in exon 3 (c.145G>A p.G49R). We also examined 42 reported cases on the clinical characteristics and neurophysiological and imaging studies of patients with known ALS2 gene mutations sourced from PubMed. This showed that an overlap of phenotypic manifestations can exist in patients with infantile ascending hereditary spastic paraplegia, juvenile primary lateral sclerosis, and juvenile amyotrophic lateral sclerosis.
doi:10.1155/2014/691515
PMCID: PMC4180207  PMID: 25302125
24.  Preaxial Polydactyly of the Foot: Variable Expression of Trisomy 13 in a Case from Central Africa 
Case Reports in Genetics  2014;2014:365031.
Trisomy 13 is a chromosomal disorder characterized by a severe clinical picture of multiple congenital anomalies. We here describe the clinical and genetic features and prognosis observed in a newborn with trisomy 13 from Central Africa. He presented the rare feature of preaxial polydactyly of the feet.
doi:10.1155/2014/365031
PMCID: PMC4164427  PMID: 25254124
25.  Pheochromocytoma in a Twelve-Year-Old Girl with SDHB-Related Hereditary Paraganglioma-Pheochromocytoma Syndrome 
Case Reports in Genetics  2014;2014:273423.
A twelve-year-old girl presented with a history of several weeks of worsening headaches accompanied by flushing and diaphoresis. The discovery of markedly elevated blood pressure and tachycardia led the child's pediatrician to consider the diagnosis of a catecholamine-secreting tumor, and an abdominal CT scan confirmed the presence of a pheochromocytoma. The patient was found to have a mutation in the succinyl dehydrogenase B (SDHB) gene, which is causative for SDHB-related hereditary paraganglioma-pheochromocytoma syndrome. Herein, we describe her presentation and medical management and discuss the clinical implications of SDHB deficiency.
doi:10.1155/2014/273423
PMCID: PMC4156988  PMID: 25215250

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