A Homozygous Missense Mutation in &lt;b&gt;&lt;i&gt;FANCA&lt;/i&gt;&lt;/b&gt; Gene in a 46,XY Female with Gonadal Dysgenesis

Mazen, Inas; McElreavey, Kenneth; Eid, Maha M.; Bashamboo, Anu; Kamah, Ghada

doi:10.1159/000491407

Cited by 3 publications

(1 citation statement)

References 24 publications

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“…A homozygous rare variant, p.Pro1411Leu (c.4232C > T), involving FANCA gene was detected in a 46,XY gonadal dysgenesis female patient presenting with atypical external genitalia and microcephaly. This variant was found to be inherited from the heterozygous parents (Mazen et al, 2018). The phenotype of Fanconi anemia patients is highly variable and may be associated with varying degrees of skeletal, genital, renal, and central nervous system anomalies.…”

Section: Discussionmentioning

confidence: 99%

Advances in genomic diagnosis of a large cohort of Egyptian patients with disorders of sex development

Mazen

Mekkawy²,

Kamel³

et al. 2021

American J of Med Genetics Pt A

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Disorders/differences of sex development (DSD) comprise a group of congenital disorders that affect the genitourinary tract and usually involve the endocrine and reproductive system. The aim of this work was to identify genetic variants responsible for disorders of human urogenital development in a cohort of Egyptian patients. This three‐year study included 225 patients with various DSD forms, referred to the genetic DSD and endocrinology clinic, National Research Centre, Egypt. The patients underwent thorough clinical examination, hormonal and imaging studies, detailed cytogenetic and fluorescence in situ hybridization analysis, and molecular sequencing of genes known to commonly cause DSD including AR, SRD5A2, 17BHSD3, NR5A1, SRY, and WT1. Whole exome sequencing (WES) was carried out for 18 selected patients. The study revealed a high rate of sex chromosomal DSD (33%) with a wide array of cytogenetic abnormalities. Sanger sequencing identified pathogenic variants in 33.7% of 46,XY patients, while the detection rate of WES reached 66.7%. Our patients showed a different mutational profile compared with that reported in other populations with a predominance of heritable DSD causes. WES identified rare and novel pathogenic variants in NR5A1, WT1, HHAT, CYP19A1, AMH, AMHR2, and FANCA and in the X‐linked genes ARX and KDM6A. In addition, digenic inheritance was observed in two of our patients and was suggested to be a cause of the phenotypic variability observed in DSD.

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Section: Discussionmentioning

confidence: 99%

Advances in genomic diagnosis of a large cohort of Egyptian patients with disorders of sex development

Mazen

Mekkawy²,

Kamel³

et al. 2021

American J of Med Genetics Pt A

Self Cite

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In silico study of missense variants of FANCA, FANCC and FANCG genes reveals high risk deleterious alleles predisposing to Fanconi anemia pathogenesis

Shahid

Azfaralariff

Zubair

et al. 2022

Gene

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Bioinformatics analysis and verification of hub genes in 46,XY, disorders of sexual development

Cao

Liu

et al. 2023

Reprod. Fertil. Dev.

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Context 46,XY, disorders of sexual development (46,XY, DSD) is a congenital genetic disease whose pathogenesis is complex and clinical manifestations are diverse. The existing molecular research has often focused on single-centre sequencing data, instead of prediction based on big data. Aims This work aimed to fully understand the pathogenesis of 46,XY, DSD, and summarise the key pathogenic genes. Methods Firstly, the potential pathogenic genes were identified from public data. Secondly, bioinformatics was used to predict pathogenic genes, including hub gene analysis, protein–protein interaction (PPI) and function enrichment analysis. Lastly, the genomic DNA from two unrelated families were recruited, next-generation sequencing and Sanger sequencing were performed to verify the hub genes. Key results A total of 161 potential pathogenic genes were selected from MGI and PubMed gene sets. The PPI network was built which included 144 nodes and 194 edges. MCODE 4 was selected from PPI which scored the most significant P-value. The top 15 hub genes were ranked and identified by Cytoscape. Furthermore, three variants were found on SRD5A2 gene by genome sequencing, which belonged to the prediction hub genes. Conclusions Our results indicate that occurrence of 46,XY, DSD is attributed to a variety of genes. Bioinformatics analysis can help us predict the hub genes and find the most core network MCODE model. Implications Bioinformatic predictions may provide a novel perspective on better understanding the pathogenesis of 46,XY, DSD.

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A Homozygous Missense Mutation in <b><i>FANCA</i></b> Gene in a 46,XY Female with Gonadal Dysgenesis

Cited by 3 publications

References 24 publications

Advances in genomic diagnosis of a large cohort of Egyptian patients with disorders of sex development

Advances in genomic diagnosis of a large cohort of Egyptian patients with disorders of sex development

In silico study of missense variants of FANCA, FANCC and FANCG genes reveals high risk deleterious alleles predisposing to Fanconi anemia pathogenesis

Bioinformatics analysis and verification of hub genes in 46,XY, disorders of sexual development

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