scholarly journals Simultaneous Identification of Both MFSD8 and RDH12 Pathogenic Variants in a Chinese Family Affected With Retinitis Pigmentosa

2021 ◽  
Vol 12 ◽  
Author(s):  
Yihui Wang ◽  
Yanling Teng ◽  
Desheng Liang ◽  
Zhuo Li ◽  
Lingqian Wu
Keyword(s):  
Retinitis Pigmentosa ◽  
Molecular Genetic ◽  
Cerebellar Atrophy ◽  
Compound Heterozygous Mutation ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Pathogenic Variants ◽  
Reproductive Counseling

Retinitis pigmentosa (RP) is characterized by tremendous genetic and phenotypic heterogeneity. Here, we investigate the pathogeny of RP in a family to provide evidence for genetic and reproductive counseling for families. Although this pregnant woman of 8+3 weeks presented with RP, her first baby was born with RP, epilepsy, and cerebellar atrophy. The research identified a compound heterozygous mutation (c.998+3_998+6del/deletion) in the MFSD8 gene of the first born, explaining the cause of the proband’s disease, which cannot explain the mother’s. Then, a homozygous mutation c.343+1G > A in RDH12 of the mother was found. RT-PCR is employed to find that there is a skipping of exon 10 in MFSD8 and a 15-nucleotide retention of intron5 in RDH12. The coexistence of two independent instances of RP caused by distinct genes in one pedigree is demonstrated. Based on the diagnosis, a prenatal diagnosis performed on the fetus found that the fetus’s MFSD8 is affected by the same mutation as the proband. The research underscoring the complexity of RP and the need for the combination of extensive molecular genetic testing and clinical characterization in addition expands the spectrum of MFSD8 mutations. Finally, it is expected that the family members would be prevented from reproducing children with the similar disease.

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 Novel compound heterozygous mutation in the CNGA1 gene underlie autosomal recessive retinitis pigmentosa in a Chinese family

2016 ◽  
Vol 36 (1) ◽  
Author(s):  
Xin Jin ◽  
Ling-Hui Qu ◽  
Bao-Ke Hou ◽  
Hai-Wei Xu ◽  
Xiao-Hong Meng ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Autosomal Recessive ◽  
Protein Product ◽  
Compound Heterozygous Mutation ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Rod Photoreceptors ◽  
Gene Coding ◽  
Compound Mutation

A novel compound mutation in CNGA1 gene, coding for the cGMP-gated ion channel protein, results in a protein product that is not targeted to the plasma membrane, which would be deleterious to rod photoreceptors leading to retinitis pigmentosa (RP).

scholarly journals BETA-GLOBIN GENE MUTATIONS IN TURKISH CHILDREN WITH BETA-THALASSEMIA: RESULTS FROM A SINGLE CENTER STUDY

2013 ◽  
Vol 5 (1) ◽  
pp. e2013055 ◽  
Author(s):  
Ali Fettah ◽  
Cengiz Bayram ◽  
Nese Yarali ◽  
Pamir Isik ◽  
Abdurrahman Kara ◽  
...  
Keyword(s):  
Globin Gene ◽  
Gene Mutations ◽  
Thalassemia Major ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Thalassemia Intermedia ◽  
Turkish Children ◽  
Tertiary Center

Introduction: The beta thalassemias are common genetic disorders in Turkey and in this retrospective study our aim was to evaluate β-globin chain mutations and the phenotypic severity of β-thalassemia patients followed-up in our hospital, a tertiary center which serves patients from all regions of Turkey. Materials and Methods: 106 pediatric patients were analysed for β-globin gene mutations by using DNA analysis. Patients were classified as having β-thalassemia major or β-thalassemia intermedia based on age at diagnosis, transfusion frequency and lowest hemoglobin concentration in between transfusions. Results: There were 106 patients (52.8% female and 47.2% male) with a mean age of 11.2±5 years (1.6 – 22.3 years). Eighty-four (79.2%) patients had β-thalassemia major, whereas the remaining 22 patients (20.8%) were identified as having β-thalassemia intermedia. Overall, 18 different mutations were detected on 212 alleles. The most frequently encountered mutation was IVS I.110 (G>A) (35.3%), followed by Codon 8 del-AA (10.4%), IVS II.1 (G>A) (8%), IVS I.1 (G>A) (7.5%), Codon 39 (C>T) (7.1%) and Codon 5 (-CT) (6.6%), which made up 79.4% of observed mutations. According to present results, IVS I.110 (G>AA) was the most frequent mutation observed in this study, as in other results from Turkey. Evaluation of β-thalassemia mutations in 106 patients with 212 alleles, revealed the presence of homozygous mutation in 85 patients (80.2%) and compound heterozygous mutation in 21 patients (19.8%). The mutations detected in patients with homozygous mutation were IVS I.110 (G>A) (38.8%), Codon 8 del –AA (11.8%), IVS II.1 (G>A) (8.2%) and IVS I.1 (G>A) (8.2%). Observed mutations in the compound heterozygotes were Codon 39 (C>T)/Codon 41-42 (-CTTT) (14.3%), IVS I.110 (G>A)/Codon 39(C>T) (14.3%), IVS I.110 (G>A)/Codon 44(-C) (14.3%), and IVS II.745 (C>G)/ 5’UTR + 22 (G>A) (9.5%). Conclusion: Our hospital is a tertiary referral center that provides care to patients from all over the country, and thus the distribution of mutations observed in the current study is significant in term of representing that of the country as a whole.

scholarly journals A novel compound heterozygous mutation in the GJB2 gene is associated with non-syndromic hearing loss in a Chinese family

2018 ◽  
Vol 12 (5) ◽  
pp. 470-475 ◽  
Author(s):  
Haiou Jiang ◽  
Youya Niu ◽  
Lingfeng Qu ◽  
Xueshuang Huang ◽  
Xinlong Zhu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Compound Heterozygous Mutation ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Syndromic Hearing Loss ◽  
I Gene

scholarly journals Genetic Examination for Fetuses with Increased Fetal Nuchal Translucency by Genomic Technology

2020 ◽  
Vol 160 (2) ◽  
pp. 57-62
Author(s):  
Shuya Xue ◽  
Huanchen Yan ◽  
Jingsi Chen ◽  
Nan Li ◽  
Jiayan Wang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Detection Rate ◽  
Nuchal Translucency ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Chromosomal Microarray Analysis ◽  
Chromosomal Anomalies ◽  
Crown Rump Length ◽  
Pathogenic Variants

This study aims to investigate the value of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in fetuses with increased nuchal translucency (defined as NT above the 95th centile for the crown-rump length). A total of 374 singleton pregnancies with gestational ages ranging from 11 to 13 + 6 weeks were investigated. Ultrasound displayed increased NT and no detectable structural malformations in these fetuses. Pregnancies were divided into 4 groups according to the NT values: 95th centile-3.4 mm (114 cases); 3.5-4.4 mm (150 cases); 4.5-5.4 mm (55 cases); and ≥5.5 mm (55 cases). The possible chromosomal anomalies were all analyzed by CMA first. Furthermore, 24 cases with increased NT but negative CMA results were investigated by WES, and the outcomes were followed up. Among all the 374 cases, causative genetic defects were detected in 100/374 (26.7%) of the cases along with 9 variants of unknown significance (VOUS) by CMA. CMA testing yielded 30 pathogenic variants (30/55), accounting for a detection rate of 54.5%, and 1 VOUS in the group of NT ≥5.5 mm, indicating the highest detection rate in the 4 groups. The 24 cases of the CMA negative sub-cohort with WES analysis further yielded 2 VOUS and 3 likely pathogenic variants, including 2 dominant de novo mutations in SOS1 and ECE1 and 1 recessive inherited compound heterozygous mutation in PIGN, which are associated with cardiac defects. All 3 cases opted for termination of pregnancy (TOP). In addition, 2 cases with increased NT were negative by both CMA and WES analysis, and fetal demise occurred. In conclusion, for the investigation of fetuses with increased NT exome sequencing is suggested to be considered in cases with negative CMA findings. However, appropriate genetic counseling should be given to optimizing its utilization in prenatal diagnosis.

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