scholarly journals Unveiling the 46,XY disorder of sex development patients family with a novel mutation in the GATA4 gene

2021 ◽  
Author(s):  
Liwei Li ◽  
Hui Yang ◽  
Junhong Zhang ◽  
Huijing Lv ◽  
Qing Li ◽  
...  
Keyword(s):  
Karyotype Analysis ◽  
Novel Mutation ◽  
Binding Protein ◽  
Gonadal Development ◽  
Heterozygous Mutation ◽  
Disorder Of Sex Development ◽  
First Report ◽  
Sex Development ◽  
Physical Examinations

Abstract Background GATA-binding protein 4 (GATA4) is the critical regulator in gonadal development and its mutation has been reported related with 46,XY disorder of sex development (DSD). Here, we found the two Chinese cases with 46,XY DSD carried the GATA4 mutation. Physical examinations, B-ultrasound and Karyotype analysis were performed and confirmed the two patients with 46,XY DSD. Results Sequencing were performed and the heterozygous mutation p.Gly375Arg in GATA4 gene was identified in the 2 cases with 46,XY DSD. Their mother was identified carrying the p.Gly375Arg mutation in GATA4 protein. However, their father and litter sister without 46,XY DSD didn’t be found carrying the p.Gly375Arg mutation in GATA4 gene. Conclusion This is the first report that the case with 46,XY DSD carried the mutation Gly375Arg in the GATA4 gene. Our

46,XY Disorder of Sex Development in a Sudanese Patient Caused by a Novel Mutation in theHSD17B3Gene

2014 ◽  
Vol 8 (4) ◽  
pp. 151-155 ◽  
Author(s):  
Mona Ellaithi ◽  
Ralf Werner ◽  
Felix G. Riepe ◽  
Nils Krone ◽  
Alexandra E. Kulle ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Disorder Of Sex Development ◽  
Sex Development

scholarly journals Mutational Analysis of Compound Heterozygous Mutation P.q6x/p.h232r in Srd5a2 Causing 46,xy Disorder of Sex Development

2022 ◽  
Author(s):  
Hui Yang ◽  
Liwei Li ◽  
Junhong Zhang ◽  
Qing Li ◽  
Li Qiao ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Mutational Analysis ◽  
Catalytic Efficiency ◽  
Hek293 Cells ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Disorder Of Sex Development ◽  
Sex Development ◽  
The Family

Abstract Background: Over 100 mutations in the SRD5A2 gene have been identified in subjects with 46,XY disorder of sex development (DSD). Exploration of SRD5A2 mutations and elucidation of the molecular mechanisms behind their effects should reveal the functions of the domains of the 5α-reductase 2 enzyme and identify the cause of 46,XY DSD. Previously, we reported a novel compound heterozygous p.Q6X/p.H232R mutation of the SRD5A2 gene in a case with 46,XY DSD. Whether the compound heterozygous p.Q6X/p.H232R mutation in this gene causes 46,XY DSD requires further exploration. Results: To clarify the cause of 46,XY DSD in the affected family focused on here, SRD5A2 sequencing was performed. Heterozygous p.H232R mutation was identified in the proband’s father, so we concluded that this mutation originated from the paternal side of the family and did not cause 46,XY DSD. Meanwhile, heterozygous p.Q6X mutation was identified in the proband’s mother, maternal uncle, and maternal grandfather, indicating that this mutation originated from maternal side of the family and did not cause 46,XY DSD. To clarify the effect of the p.H232R mutation in SRD5A2 on dihydrotestosterone (DHT) production, p.H232R mutant SRD5A2 plasmids were transfected into HEK293 cells. LC-MS indicated that DHT production decreased compared with that in cells transfected with wild-type SRD5A2.Conclusions: Our findings confirmed that the compound heterozygous p.Q6X/p.H232R mutation in the SRD5A2 gene is the cause of 46,XY DSD. p.H232R mutation reduced DHT production while attenuating the catalytic efficiency of the 5α-reductase 2 enzyme.

scholarly journals Mutational Analysis of a Novel Mutation (p.H232R) in the SRD5A2 Causing 46,XY Disorder of Sex Development

2021 ◽  
Author(s):  
Liwei Li ◽  
Junhong Zhang ◽  
Qing Li ◽  
Li Qiao ◽  
Pengcheng Li ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Mutational Analysis ◽  
Novel Mutation ◽  
Catalytic Efficiency ◽  
Hek293 Cells ◽  
Compound Heterozygous ◽  
Wild Type ◽  
Disorder Of Sex Development ◽  
Maternal Grandfather ◽  
Sex Development

Abstract Background: Over 100 mutations in SRD5A2 gene have been identified in subjects with 46,XY DSD. Exploring SRD5A2 mutation and elucidating its molecular mechanism will find the domains function of 5α-reductase 2 enzyme and identify the cause of 46,XY DSD. Previously, we reported a novel compound heterozygous p.H232R/p.Q6X mutation of SRD5A2 gene in a case with 46,XY DSD. Whether the compound heterozygous p.Q6X/p.H232R mutation in SRD5A2 gene causes 46,XY DSD occurrence is needed to be further explored. Results: In order to clarify the cause of 46,XY DSD in the case’s family, SRD5A2 sequencing were performed. The heterozygous p.H232R mutation were identified in the case’s father, so we concluded that the heterozygous p.H232R mutation originated from paternal family and didn’t cause 46,XY DSD occurrence. The heterozygous p.Q6X mutation were identified in the case’s mother, maternal uncle and maternal grandfather, indicating that the heterozygous p.Q6X mutation descended from maternal family and didn’t cause 46,XY DSD occurrence. In order to clarify p.H232R mutation in SRD5A2 on DHT production, p.H232R mutant SRD5A2 plasmids were transfected with HEK293 cells and LC-MS detected that DHT production decreased compared with wild-type SRD5A2 infected ones.Conclusions: Our findings confirmed that the compound heterozygous p.Q6X/p.H232R mutation in SRD5A2 gene is the cause of 46,XY DSD. p.H232R mutation reduced DHT production while attenuated 5α-reductase 2 enzymatic catalytic efficiency.

scholarly journals Identification of a novel mutation in the SRD5A2 gene of one patient with 46,XY disorder of sex development

2018 ◽  
Vol 20 (5) ◽  
pp. 518
Author(s):  
Shu-Jun Li ◽  
Xiao-Wei Dou ◽  
Shu-Ping Li ◽  
Li-Wei Li ◽  
Ming-Xia Sun ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Disorder Of Sex Development ◽  
Sex Development ◽  
Srd5a2 Gene

scholarly journals Novel mutation in the TGFBI gene in a Moroccan family with atypical corneal dystrophy: a case report

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yahya Benbouchta ◽  
Imane Cherkaoui Jaouad ◽  
Habiba Tazi ◽  
Hamza Elorch ◽  
Mouna Ouhenach ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Symptoms ◽  
Age Of Onset ◽  
Novel Mutation ◽  
Corneal Dystrophy ◽  
Heterozygous Mutation ◽  
Large Variability ◽  
Whole Exome ◽  
Moroccan Family

Abstract Background Corneal dystrophies (CDs) are a heterogeneous group of bilateral, genetically determined, noninflammatory bilateral corneal diseases that are usually limited to the cornea. CD is characterized by a large variability in the age of onset, evolution and visual impact and the accumulation of insoluble deposits at different depths in the cornea. Clinical symptoms revealed bilateral multiple superficial, epithelial, and stromal anterior granular opacities in different stages of severity among three patients of this family. A total of 99 genes are involved in CDs. The aim of this study was to identify pathogenic variants causing atypical corneal dystrophy in a large Moroccan family and to describe the clinical phenotype with severely different stages of evolution. Case presentation In this study, we report a large Moroccan family with CD. Whole-exome sequencing (WES) was performed in the three affected members who shared a phenotype of corneal dystrophy in different stages of severity. Variant validation and familial segregation were performed by Sanger sequencing in affected sisters and mothers and in two unaffected brothers. Whole-exome sequencing showed a novel heterozygous mutation (c.1772C > A; p.Ser591Tyr) in the TGFBI gene. Clinical examinations demonstrated bilaterally multiple superficial, epithelial and stromal anterior granular opacities in different stages of severity among three patients in this family. Conclusions This report describes a novel mutation in the TGFBI gene found in three family members affected by different phenotypic aspects. This mutation is associated with Thiel-Behnke corneal dystrophy; therefore, it could be considered a novel phenotype genotype correlation, which will help in genetic counselling for this family.

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