Identification of 8 Novel Mutations in Nephrogenesis-Related Genes in Chinese Han Patients with Unilateral Renal Agenesis

2017 ◽  
Vol 46 (1) ◽  
pp. 55-63 ◽  
Author(s):  
Hangdi Wu ◽  
Qian Xu ◽  
Jingyuan Xie ◽  
Jun Ma ◽  
Panpan Qiao ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Renal Agenesis ◽  
Clinical Manifestations ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Urogenital System ◽  
Healthy Controls ◽  
Missense Mutations ◽  
Chinese Han ◽  
Unilateral Renal Agenesis

Background: Few genetic studies have focused on unilateral renal agenesis (URA), which is a disorder with insidious clinical manifestations and a tendency to result in renal failure. We aimed to detect pathogenic mutations in nephrogenesis-related genes, which were identified by a literature review conducted among a large cohort of Chinese Han patients with URA. Methods: Totally, 86 unrelated URA patients were included. All URA patients were diagnosed by employing radiological methods. Patients with a solitary kidney owing to nephrectomy or renal atrophy due to secondary factors were excluded. Nine (10.5%) patients had a family history of abnormal nephrogenesis. Fifteen (17.4%) had other malformations in the urogenital system. All coding exons and adjacent intron regions of 25 genes were analyzed using next-generation sequencing and validated by Sanger sequencing and 100 ethnically matched healthy controls. Results: Ten conserved mutations (9 missense mutations and 1 deletion mutation) were identified in SALL1, EYA1, RET, HNF1B, DSTYK, WNT4, and SIX5. All mutations were novel or rare (frequency <0.1%) in the public databases and absent from the 100 healthy controls. Nine patients carried mutations in candidate genes. Most of the patients carried one single heterozygous mutation, except for 2, who respectively carried compound heterozygous mutations and 2 single heterozygous mutations. In addition, 2 patients shared the same mutation in DSTYK. Conclusion: A total of 10.5% of our URA cases could be explained by mutations in our candidate genes. The mutations in nephrogenesis-related genes in the Chinese Han patients with URA had a decentralized distribution without any hotspot mutations.

scholarly journals Identification of two novel CAKUT-causing genes by massively parallel exon resequencing of candidate genes in patients with unilateral renal agenesis

2012 ◽  
Vol 81 (2) ◽  
pp. 196-200 ◽  
Author(s):  
Pawaree Saisawat ◽  
Velibor Tasic ◽  
Virginia Vega-Warner ◽  
Elijah O. Kehinde ◽  
Barbara Günther ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Renal Agenesis ◽  
Massively Parallel ◽  
Unilateral Renal Agenesis

scholarly journals Unique three-site compound heterozygous mutation in the WFS1 gene in Wolfram syndrome

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ziyu Ren ◽  
Jixiu Yi ◽  
Min Zhong ◽  
Yunting Wang ◽  
Qicong Liu ◽  
...  
Keyword(s):  
Genetic Disease ◽  
Target Genes ◽  
Novel Mutation ◽  
Clinical Manifestations ◽  
Wolfram Syndrome ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Compound Heterozygous Mutations ◽  
Wfs1 Gene

Abstract Background Wolfram syndrome (WFS) is a rare autosomal recessive genetic disease whose main cause is mutations in the WFS1 and CISD2 genes. Its characteristic clinical manifestations are diabetes insipidus, diabetes mellitus, optic atrophy and deafness. Methods In this study, two patients from this particular family underwent complete routine biochemical and ophthalmic tests. Blood, urine, routine stool test, visual acuity (VA) examination, visual field assessment, funduscope, optical coherence tomography and periorbital magnetic resonance imaging (MRI) scans were performed for each patient to evaluate whether the nerve fiber layer around the optic nerve head was atrophied and next-generation sequencing of target genes was performed in two patients. Results When the patients were diagnosed with Wolfram syndrome, their genetic analyses suggested unique three-site compound heterozygous mutations (c.2314C > T + c.2194C > T + c.2171C > T) in exon 8 of both patients’ chromosome 4. One mutation (c.2314C > T) was a novel mutation in the known reports of Wolfram syndrome. As a degenerative genetic disease, the types of gene mutations in the Chinese population are generally homozygous mutations at the unit point or compound heterozygous mutations at two nucleotide change sites. However, the two patients reported in this study are the first known cases of compound heterozygous mutations with three mutation sites coexisting on the WFS1 gene in China or even globally. Conclusions This study expands the phenotypic spectrum of Wolfram syndrome and may reveal a novel mutation pattern of pathogenesis of Wolfram syndrome. The implications of this discovery are valuable in the clinical diagnosis, prognosis, and treatment of patients with WFS1.

Clinical and molecular genetic characterization of two patients with mutations in the phosphoglucomutase 1 (PGM1) gene

2018 ◽  
Vol 31 (7) ◽  
pp. 781-788 ◽  
Author(s):  
Yu Ding ◽  
Niu Li ◽  
Gouying Chang ◽  
Juan Li ◽  
Ruen Yao ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Chinese Han ◽  
Targeted Gene Sequencing ◽  
Molecular Genetic Characterization

Abstract Background The phosphoglucomutase 1 (PGM1) enzyme plays a central role in glucose homeostasis by catalyzing the inter-conversion of glucose 1-phosphate and glucose 6-phosphate. Recently, PGM1 deficiency has been recognized as a cause of the congenital disorders of glycosylation (CDGs). Methods Two Chinese Han pediatric patients with recurrent hypoglycemia, hepatopathy and growth retardation are described in this study. Targeted gene sequencing (TGS) was performed to screen for causal genetic variants in the genome of the patients and their parents to determine the genetic basis of the phenotype. Results DNA sequencing identified three variations of the PGM1 gene (NM_002633.2). Patient 1 had a novel homozygous mutation (c.119delT, p.Ile40Thrfs*28). In patient 2, we found a compound heterozygous mutation of c.1172G>T(p.Gly391Val) (novel) and c.1507C>T(p.Arg503*) (known pathogenic). Conclusions This report deepens our understanding of the clinical features of PGM1 mutation. The early molecular genetic analysis and multisystem assessment were here found to be essential to the diagnosis of PGM1-CDG and the provision of timely and proper treatment.

scholarly journals Hereditary Spherocytosis Caused by a Novel Compound Heterozygous Mutation of the SPTA1 Gene and Autoimmune Hepatitis in a Pediatric Patient

2021 ◽  
Author(s):  
Yu-mei Qin ◽  
Yan-yun Chen ◽  
Lin Liao ◽  
Yang-yang Wu ◽  
Min Chen ◽  
...  
Keyword(s):  
Autoimmune Hepatitis ◽  
Hereditary Spherocytosis ◽  
Clinical Manifestations ◽  
Liver Function Tests ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Concomitant Disease ◽  
Genetic Characteristics ◽  
Paternal Grandmother

Abstract Objective: Patients suffering from both hereditary spherocytosis (HS) and autoimmune hepatitis (AIH) are very rare. We analyzed the clinical and genetic characteristics of a seven-year-old girl with yellow sclerae and abnormal liver function tests, but no further symptoms. Methods: Blood samples were collected from the proband, her parents, and her paternal grandmother, and analyzed using routine laboratory tests, as well as subjected to next-generation and Sanger sequencing.Results: Compound heterozygous mutations of the spectrin alpha, erythrocytic 1 (SPTA1) gene were identified in the proband. Thec.134G>A (p.R45K) and c.6544G>C (p.D2182H) mutations were inherited from her mother and father, respectively. The proband’s father and paternal grandmother had the same mutation. Neither mutation is described in the Human Gene Mutation Database. Conclusions: HS has clinical manifestations similar to AIH, it may be difficult to diagnose when it coexists with AIH. When laboratory results cannot be explained by autoimmune liver disease alone, the possibility of a concomitant disease should be considered. Pedigree investigation and genetic analyses might be required to arrive at the final diagnosis.

scholarly journals Case Report: A Novel Compound Heterozygous Mutation of the FRMD4A Gene Identified in a Chinese Family With Global Developmental Delay, Intellectual Disability, and Ataxia

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuhua Pan ◽  
Xiaoling Guo ◽  
Xiaoqiang Zhou ◽  
Yue Liu ◽  
Jingli Lian ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Intellectual Development ◽  
Scaffolding Protein ◽  
Compound Heterozygous Mutation ◽  
Global Developmental Delay ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Missense Mutations ◽  
Sequencing Data

Background: FERM domain-containing protein 4A (FRMD4A) is a scaffolding protein previously proposed to be critical in the regulation of cell polarity in neurons and implicated in human intellectual development.Case Presentation: We report a case of a 3-year-old boy with corpus callosum anomaly, relative macrocephaly, ataxia, and unexplained global developmental delay. Here, compound heterozygous missense mutations in the FRMD4A gene [c.1830G&gt;A, p.(Met610Ile) and c.2973G&gt;C, p.(Gln991His)] were identified in the proband, and subsequent familial segregation showed that each parent had transmitted a mutation.Conclusions: Our results have confirmed the associations of mutations in the FRMD4A gene with intellectual development and indicated that for patients with unexplained global developmental delay, the FRMD4A gene should be included in the analysis of whole exome sequencing data, which can contribute to the identification of more patients affected by this severe phenotypic spectrum.

scholarly journals Novel PTPRQ Mutations Identified in Three Congenital Hearing Loss Patients With Various Types of Hearing Loss

2015 ◽  
Vol 124 (1_suppl) ◽  
pp. 184S-192S ◽  
Author(s):  
Naoko Sakuma ◽  
Hideaki Moteki ◽  
Hela Azaiez ◽  
Kevin T. Booth ◽  
Masahiro Takahashi ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Clinical Manifestations ◽  
Vestibular Dysfunction ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Caloric Test ◽  
Compound Heterozygous ◽  
Site Mutation ◽  
Vestibular Evoked Myogenic Potential ◽  
Phenotypic Features

Objectives: We present 3 patients with congenital sensorineural hearing loss (SNHL) caused by novel PTPRQ mutations, including clinical manifestations and phenotypic features. Methods: Two hundred twenty (220) Japanese subjects with SNHL from unrelated and nonconsanguineous families were enrolled in the study. Targeted genomic enrichment with massively parallel DNA sequencing of all known nonsyndromic hearing loss genes was performed to identify the genetic cause of hearing loss. Results: Four novel causative PTPRQ mutations were identified in 3 cases. Case 1 had progressive profound SNHL with a homozygous nonsense mutation. Case 2 had nonprogressive profound SNHL with a compound heterozygous mutation (nonsense and missense mutation). Case 3 had nonprogressive moderate SNHL with a compound heterozygous mutation (missense and splice site mutation). Caloric test and vestibular evoked myogenic potential (VEMP) test showed vestibular dysfunction in Case 1. Conclusion: Hearing loss levels and progression among the present cases were varied, and there seem to be no obvious correlations between genotypes and the phenotypic features of their hearing loss. The PTPRQ mutations appeared to be responsible for vestibular dysfunction.

Hepatic Manifestations of 3-Hydroxy-3-Methylglutaryl-Coenzyme-A Lyase Deficiency in Saudi Patients: Experience of a Tertiary Care Center

2020 ◽  
Author(s):  
Sinan Holdar ◽  
Zuhair Rahbeeni ◽  
Khushnooda Ramzan ◽  
Faiqa Imtiaz
Keyword(s):  
Coenzyme A ◽  
Care Center ◽  
Tertiary Care ◽  
Clinical Manifestations ◽  
Research Centre ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Laboratory Findings ◽  
Saudi Patients

Abstract3-Hydroxy-3-methylglutaryl-coenzyme-A lyase (HMGCL) deficiency, a rare autosomal recessive disorder, is caused by a homozygous or compound heterozygous mutation in the HMGCL gene (chromosome 1p36.11). HMGCL catalyzes the final step of leucine degradation and plays a key role in ketone body formation. Several studies have reported general hepatic findings (e.g., hepatomegaly) in patients with HMGCL deficiency, but currently, there are no available data regarding the incidence and epidemiology of liver involvement. The main objective of our study was to investigate the overall clinical manifestations, laboratory findings, genotype, and presence of hepatic involvement in Saudi patients with HMGCL deficiency. A retrospective chart review of patients with HMGCL deficiency including those with a documented hepatic manifestation was performed at the King Faisal Specialist Hospital & Research Centre in Riyadh, Saudi Arabia. We evaluated 50 cases of HMGCL deficiency. Hepatic findings were found in 17 patients at the time of diagnosis. The mean age of hepatic presentation was 135 days, and the median age was 56 days (range: 2–315 days). Hepatomegaly was found in 65%, abnormal biochemical profile in 47%, and an abnormal imaging in 53% of patients. The most frequent mutation in this cohort was the p.Arg41Gln founder mutation (59%). In comparison to data from the current literature, HMGCL deficiency can be considered as a diagnostic metabolite for hepatic manifestations and requires appropriate evaluation, including molecular genetic analysis.

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