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1.  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
2.  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
3.  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
4.  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
5.  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
6.  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
7.  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
8.  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
9.  Novel Mutation in the PKHD1 Gene Diagnosed Prenatally in a Fetus with Autosomal Recessive Polycystic Kidney Disease 
Case Reports in Genetics  2014;2014:517952.
We report a 29-year-old gravida 2, para 0100, who presented at 19 weeks and 4 days of gestation for ultrasound to assess fetal anatomy. Routine midtrimester fetal anatomy ultrasound revealed enlarged, hyperechoic fetal kidneys and normal amniotic fluid index. Follow-up ultrasound at 23 weeks and 5 days revealed persistently enlarged, hyperechoic fetal kidneys. Progressive oligohydramnios was not evident until 29 weeks of gestation, with anhydramnios noted by 35 weeks of gestation. Amniocentesis was performed for karyotype and to search for mutations in the PKHD1 for the presumptive diagnosis of autosomal recessive polycystic kidney disease (ARPKD). In our patient, a maternally inherited, previously reported pathogenic missense mutation in the PKHD1 gene, c.10444C>T, was identified. A second, previously unreported de novo mutation, c.5909-2delA, was also identified. This mutation affects the canonical splice site and is most likely pathogenic. Our case highlights PKHD1 allelic heterogeneity and the importance of genetic testing in the prenatal setting where many other genetic etiologies can phenocopy ARPKD.
doi:10.1155/2014/517952
PMCID: PMC4120792  PMID: 25114813
10.  Concomitant Alpha- and Gamma-Sarcoglycan Deficiencies in a Turkish Boy with a Novel Deletion in the Alpha-Sarcoglycan Gene 
Case Reports in Genetics  2014;2014:248561.
Limb-girdle muscular dystrophy type 2D (LGMD-2D) is caused by autosomal recessive defects in the alpha-sarcoglycan gene located on chromosome 17q21. In this study, we present a child with alpha-sarcoglycanopathy and describe a novel deletion in the alpha-sarcoglycan gene. A 5-year-old boy had a very high serum creatinine phosphokinase level, which was determined incidentally, and a negative molecular test for the dystrophin gene. Muscle biopsy showed dystrophic features. Immunohistochemistry showed that there was diminished expression of alpha- and gamma-sarcoglycans. DNA analysis revealed a novel 7 bp homozygous deletion in exon 3 of the alpha-sarcoglycan gene. His parents were consanguineous heterozygous carriers of the same deletion. We believe this is the first confirmed case of primary alpha-sarcoglycanopathy with a novel deletion in Turkey. In addition, this study demonstrated that both muscle biopsy and DNA analysis remain important methods for the differential diagnosis of muscular dystrophies because dystrophinopathies and sarcoglycanopathies are so similar.
doi:10.1155/2014/248561
PMCID: PMC4090428  PMID: 25050186
11.  Complex Variant of Philadelphia Translocation Involving Chromosomes 9, 12, and 22 in a Case with Chronic Myeloid Leukaemia 
Case Reports in Genetics  2014;2014:691630.
Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder included in the broader diagnostic category of myeloproliferative neoplasms, associated with fusion by BCR gene at chromosome 22q11 to ABL1 gene at chromosome 9q34 with the formation of the Philadelphia (Ph) chromosome. In 2–10% of CML cases, the fusion gene arises in connection with a variant translocation, involving chromosomes 9, 22, and one or more different chromosomes; consequently, the Ph chromosome could be masked within a complex chromosome rearrangement. In cases with variant Ph translocation a deletion on der(9) may be more frequently observed than in cases with the classical one. Herein we describe a novel case of CML with complex variant Ph translocation involving chromosomes 9, 12, and 22. We present the hematologic response and cytogenetic response after Imatinib treatment. We also speculated the mechanism which had originated the chromosome rearrangement.
doi:10.1155/2014/691630
PMCID: PMC4087276  PMID: 25045550
12.  Clinical Report of a 17q12 Microdeletion with Additionally Unreported Clinical Features 
Case Reports in Genetics  2014;2014:264947.
Copy number variations involving the 17q12 region have been associated with developmental and speech delay, autism, aggression, self-injury, biting and hitting, oppositional defiance, inappropriate language, and auditory hallucinations. We present a tall-appearing 17-year-old boy with marfanoid habitus, hypermobile joints, mild scoliosis, pectus deformity, widely spaced nipples, pes cavus, autism spectrum disorder, intellectual disability, and psychiatric manifestations including physical and verbal aggression, obsessive-compulsive behaviors, and oppositional defiance. An echocardiogram showed borderline increased aortic root size. An abdominal ultrasound revealed a small pancreas, mild splenomegaly with a 1.3 cm accessory splenule, and normal kidneys and liver. A testing panel for Marfan, aneurysm, and related disorders was negative. Subsequently, a 400 K array-based comparative genomic hybridization (aCGH) + SNP analysis was performed which identified a de novo suspected pathogenic deletion on chromosome 17q12 encompassing 28 genes. Despite the limited number of cases described in the literature with 17q12 rearrangements, our proband's phenotypic features both overlap and expand on previously reported cases. Since syndrome-specific DNA sequencing studies failed to provide an explanation for this patient's unusual habitus, we postulate that this case represents an expansion of the 17q12 microdeletion phenotype. Further analysis of the deleted interval is recommended for new genotype-phenotype correlations.
doi:10.1155/2014/264947
PMCID: PMC4060289  PMID: 24991439
13.  Intrauterine Growth Retardation Fetus with Trisomy 16 Mosaicism 
Case Reports in Genetics  2014;2014:739513.
Fetal trisomy 16 is considered uniformly lethal early in gestation. It has been reported to be associated with the variability of clinical features and outcomes. Mosaic trisomy 16 leads to a high risk of abnormality in prenatal cases. Intrauterine growth retardation (IUGR) is a common outcome of mosaic trisomy 16. Herein, we report on the case of Thai male IUGR fetus with trisomy 16 mosaicism. The fetal body was too small. Postmortem investigation of placenta revealed the abnormality including small placenta with furcated cord insertion and single umbilical cord artery. Cytogenetic study demonstrated trisomy 16 that was found 100% in placenta and only 16% in the fetal heart while other organs had normal karyotype. In addition, cardiac and other internal organs examination revealed normal morphology.
doi:10.1155/2014/739513
PMCID: PMC4052622  PMID: 24955263
14.  A Rare, Recurrent, De Novo 14q32.2q32.31 Microdeletion of 1.1 Mb in a 20-Year-Old Female Patient with a Maternal UPD(14)-Like Phenotype and Intellectual Disability 
Case Reports in Genetics  2014;2014:530134.
We present a 20-year-old female patient from Indonesia with intellectual disability (ID), proportionate short stature, motor delay, feeding problems, microcephaly, facial dysmorphism, and precocious puberty who was previously screened normal for conventional karyotyping, fragile X testing, and subtelomeric MLPA analysis. Subsequent genome wide array analysis was performed on DNA from blood and revealed a 1.1 Mb deletion in 14q32.2q32.31 (chr14:100,388,343-101,506,214; hg19). Subsequent carrier testing in the parents by array showed that the deletion had occurred de novo in the patient and that her paternal 14q32 allele was deleted. The deleted region encompasses the DLK1/GTL2 imprinted gene cluster which is consistent with the maternal UPD(14)-like phenotype of the patient. This rare, recurrent microdeletion was recently shown not to be mediated by low copy repeats, but by expanded TGG repeats, flanking the 14q32.2q32.21 deletion boundaries, a novel mechanism of recurrent genomic rearrangement. This is another example how the application of high resolution genome wide testing provides an accurate genetic diagnosis, thereby improving the care for patients and optimizing the counselling for family.
doi:10.1155/2014/530134
PMCID: PMC3985205  PMID: 24800088
15.  A Turner Syndrome Patient Carrying a Mosaic Distal X Chromosome Marker 
Case Reports in Genetics  2014;2014:597314.
A skin sample from a 17-year-old female was received for routine karyotyping with a set of clinical features including clonic seizures, cardiomyopathy, hepatic adenomas, and skeletal dysplasia. Conventional karyotyping revealed a mosaic Turner syndrome karyotype with a cell line containing a small marker of X chromosome origin. This was later confirmed on peripheral blood cultures by conventional G-banding, fluorescence in situ hybridisation and microarray analysis. Similar Turner mosaic marker chromosome cases have been previously reported in the literature, with a variable phenotype ranging from the mild “classic” Turner syndrome to anencephaly, agenesis of the corpus callosum, complex heart malformation, and syndactyly of the fingers and toes. This case report has a phenotype that is largely discordant with previously published cases as it lies at the severe end of the Turner variant phenotype scale. The observed cytogenetic abnormalities in this study may represent a coincidental finding, but we cannot exclude the possibility that the marker has a nonfunctioning X chromosome inactivation locus, leading to functional disomy of those genes carried by the marker.
doi:10.1155/2014/597314
PMCID: PMC3977098  PMID: 24778889
16.  Neurofibromatosis Type 1: A Novel NF1 Mutation Associated with Mitochondrial Complex I Deficiency 
Case Reports in Genetics  2014;2014:423071.
Background. Neurofibromatosis type 1 is a multisystemic, progressive disease, with an estimated incidence of 1/3500-2500. Mitochondrial diseases are generally multisystemic and may be present at any age, and the global prevalence is 1/8500. The diagnosis of these disorders is complex because of its clinical and genetic heterogeneity. Case Report. We present a rare case of the association of these two different genetic diseases, in which a heterozygous missense mutation in the NF1 gene was identified which had not yet been described (p.M1149 V). Additionally, the patient is suspected of carrying an unspecified mutation causing respiratory chain complex I deficiency. Clinical presentation included hypotonia, global development delay, reduced growth rate, progressive microcephaly, and numerous café-au-lait spots. Discussion. To the best of our knowledge this is the first report of complex I deficiency in a patient with neurofibromatosis type 1. It is very important to maintain a high index of suspicion for the diagnosis of mitochondrial disorders. In this patient, both the laboratory screening and muscle histology were normal and only the biochemical study of muscle allowed us to confirm the diagnosis.
doi:10.1155/2014/423071
PMCID: PMC3965950  PMID: 24711935
17.  Novel SMAD3 Mutation in a Patient with Hypoplastic Left Heart Syndrome with Significant Aortic Aneurysm 
Case Reports in Genetics  2014;2014:591516.
Aneurysms-osteoarthritis syndrome (AOS) caused by haploinsufficiency of SMAD3 is a recently described cause of syndromic familial thoracic aortic aneurysm and dissection (TAAD). We identified a novel SMAD3 mutation in a patient with hypoplastic left heart syndrome (HLHS) who developed progressive aortic aneurysm requiring surgical replacement of the neoaortic root, ascending aorta, and proximal aortic arch. Family screening for the mutation revealed that his father, who has vascular and skeletal features of AOS, and his brother, who is asymptomatic, also have the pathogenic mutation. This is the first case report of a SMAD3 mutation in a patient with hypoplastic left heart syndrome. This case highlights the importance of genetic testing for known causes of aneurysm in patients with congenital heart disease who develop aneurysmal disease as it may significantly impact the management of those patients and their family members.
doi:10.1155/2014/591516
PMCID: PMC3970455  PMID: 24711937
18.  Previously Unreported Chromosomal Aberrations of t(3;3)(q29;q23), t(4;11)(q21;q23), and t(11;18)(q10;q10) in a Patient with Accelerated Phase Ph+ CML 
Case Reports in Genetics  2014;2014:582016.
Chronic myelogenous leukemia (CML) is a clonal hematological disorder, which is characterized by the presence of the classical or variant Philadelphia translocations. During the progression to blastic phase of the disease secondary chromosomal abnormalities may emerge. Such secondary chromosomal abnormalities are nonrandom, the more frequent ones being trisomy 8 and 19, supernumerary i(17q), and extra Philadelphia chromosomes. Furthermore, a minor percentage of the patients may acquire different secondary chromosomal abnormalities including translocations between other chromosomes. We report here a patient with Ph+ CML presenting secondary chromosomal abnormalities including t(4;11)(q21;q23), t(3;3)(q29;q23) and t(11;18)(q10;q10) during the course of CML progression.
doi:10.1155/2014/582016
PMCID: PMC3965933  PMID: 24711936
19.  Microduplication of 3p26.3 Implicated in Cognitive Development 
Case Reports in Genetics  2014;2014:295359.
We report here a 34-month-old boy with global developmental delay referred for molecular karyotyping and fragile X studies. Molecular karyotype analysis revealed a microduplication in the 3p26.3 region involving part of the CHL1 and CNTN6 genes. Several deletions, one translocation, and one duplication have previously been described in this region of chromosome 3. The CHL1 gene has been proposed as a dosage-sensitive gene with a central role in cognitive development, and so the microduplication reported here appears to be implicated in our patient's phenotype.
doi:10.1155/2014/295359
PMCID: PMC3978399  PMID: 24778888
20.  Congenital Arthrogryposis: An Extension of the 15q11.2 BP1-BP2 Microdeletion Syndrome? 
Case Reports in Genetics  2014;2014:127258.
The proximal 15q11–q13 region contains 5 breakpoints (BP1–BP5). The BP1-BP2 region spans approximately 500 kb and contains four evolutionarily conserved genes. The genes in this region are known to play a role in central nervous system development and/or function. Microdeletions within the 15q11.2 BP1-BP2 region have been reported in patients with neurological dysfunction, developmental delays, behavioral problems, and dysmorphic features. We report two unrelated subjects with the 15q11.2 BP1-BP2 microdeletion and presenting with congenital arthrogryposis, a feature which has not been previously reported as part of this newly recognized microdeletion syndrome. While arthrogryposis seen in these two subjects may be coincidental, we propose that congenital arthrogryposis may result from neurological dysfunction and involvement of the microdeletion of the 15q11.2 BP1-BP2 region, further expanding the phenotype of this microdeletion syndrome. We encourage others to report patients with this chromosome microdeletion and neurological findings to further characterize the clinical phenotype.
doi:10.1155/2014/127258
PMCID: PMC3978403  PMID: 24778887
21.  A Paternally Inherited BRCA1 Mutation Associated with an Unusual Aggressive Clinical Phenotype 
Case Reports in Genetics  2014;2014:875029.
This report highlights the necessity of genetic testing, at least for BRCA1 mutations, of young females diagnosed with triple negative breast cancer, even in the absence of or limited family history. A 34-year-old female with a locally advanced, triple negative tumour, which perforated the skin, is described. At the time of diagnosis, the patient had already multiple lung metastases and although chemotherapy was started immediately, she died with rapid systemic disease progression. The patient was found to carry the BRCA1 p.E1060X mutation, which is located on exon 11 of the gene. The high penetrance of BRCA1 gene is not represented in the patient's family, since the mutation was paternally inherited. It is evident that females belonging to small families, along with paternal inheritance of pathogenic BRCA mutations that predispose for breast cancer, in most cases will probably be genetically tested only after being diagnosed with cancer.
doi:10.1155/2014/875029
PMCID: PMC3934306  PMID: 24660075
22.  An Interstitial Deletion at 10q26.2q26.3 
Case Reports in Genetics  2014;2014:505832.
We present a case of an interstitial subtelomeric 10q26 deletion in a male child with moderate developmental delay and minor dysmorphic features. Using array comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH), we have detected an interstitial deletion at 10q26.2q26.3 encompassing a 5.8 Mb region and spanning 24 genes. Interestingly, losses of this chromosome 10 region have not been previously associated with a phenotype outcome. According to an in silico evaluation, we have suggested that PPP2R2D and BNIP3 losses are likely a cause of developmental delay in the index patient. Our data allow to speculating that haploinsufficiency of these two genes in 10q26.3, which is usually ignored in the context of chromosome 10q deletions, has a phenotypic effect.
doi:10.1155/2014/505832
PMCID: PMC3932651  PMID: 24649379
23.  Apparent Homozygosity of p.Phe508del in CFTR due to a Large Gene Deletion of Exons 4–11 
Case Reports in Genetics  2014;2014:613863.
We report a classic cystic fibrosis (CF) boy with a large deletion of exons 4–11 in the cystic fibrosis transmembrane conductance regulator (CFTR) gene on one allele and p.Phe508del in exon 10 on the second allele. Both parents of Georgian and Ukrainian background had no personal or family history of the disease. The initial molecular diagnostic investigation identified the patient as homozygous for the p.Phe508del and not compatible with his parent's genetic status. The possibility of nonpaternity or uniparental disomy (UPD7) was investigated and excluded using microsatellite analysis of highly polymorphic markers on chromosome 7. Array-CGH was also performed on the patient and revealed a male profile with a subtle deletion within the CFTR gene on the long arm (q-arm) of chromosome 7 (7q31.2). The deletion was confirmed by MLPA extending from probe L02380 to probe L14978 (28.7 kb) and that was inherited from his father, while p.PheF508del was inherited from his mother. These data highlight the need for additional testing for large deletions in patients with apparent homozygosity for a mutated CFTR allele that do not match the carrier status of the parents. Not testing can lead to misdiagnosis and misinterpretation of mutation carrier status and the expected penetrance of the disorder.
doi:10.1155/2014/613863
PMCID: PMC3932727  PMID: 24649380
24.  A Case of False Negative NIPT for Down Syndrome-Lessons Learned 
Case Reports in Genetics  2014;2014:823504.
Down syndrome or trisomy 21 is the most common cause of prenatal chromosome abnormalities with approximately 50% of all reported chromosome conditions. With the successful introduction of noninvasive prenatal testing (NIPT) for Down syndrome into routine prenatal care, it is important to understand the risks, benefits, and limitations in order to guide patients in making an informed decision. Herein, we describe the first published case report of a patient whose fetus tested “negative” for Trisomy 21 by NIPT but was diagnosed postnatally with trisomy 21. We present the importance of proper pretest and posttest genetic counseling to ensure prenatal patients are able to make informed decisions and are educated appropriately about NIPT.
doi:10.1155/2014/823504
PMCID: PMC3932282  PMID: 24649382
25.  A Case of 17q21.31 Microduplication and 7q31.33 Microdeletion, Associated with Developmental Delay, Microcephaly, and Mild Dysmorphic Features 
Case Reports in Genetics  2014;2014:658570.
Concurrent cryptic microdeletion and microduplication syndromes have recently started to reveal themselves with the advent of microarray technology. Analysis has shown that low-copy repeats (LCRs) have allowed chromosome regions throughout the genome to become hotspots for nonallelic homologous recombination to take place. Here, we report a case of a 7.5-year-old girl who manifests microcephaly, developmental delay, and mild dysmorphic features. Microarray analysis identified a microduplication in chromosome 17q21.31, which encompasses the CRHR1, MAPT, and KANSL1 genes, as well as a microdeletion in chromosome 7q31.33 that is localised within the GRM8 gene. To our knowledge this is one of only a few cases of 17q21.31 microduplication. The clinical phenotype of patients with this microduplication is milder than of those carrying the reciprocal microdeletions, and suggests that the lower incidence of the former compared to the latter may be due to underascertainment.
doi:10.1155/2014/658570
PMCID: PMC3932285  PMID: 24649381

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