Mutational Profile of 10 Afflicted Egyptian Families with 17-β-HSD-3 Deficiency

Hassan, Heba; Mazen, Inas; Gad, Yehia Z.; Ali, Ola; Mekkawy, Mona; Essawi, Mona

doi:10.1159/000445311

Cited by 4 publications

(2 citation statements)

References 38 publications

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“…Similar to our findings, SRD5A2 variants were the second most frequently reported cause of 46,XY DSD in Indian populations (Nagaraja et al, 2019). We have found that 17β‐Hydroxysteroid dehydrogenases III (HSD17B3) deficiency is relatively common in our cohort with a different mutational profile compared with that observed in other populations (Hassan et al, 2016) (Table 3). In contrast, only five pathogenic variants were detected in the AR gene out of 28 patients with suspected androgen insensitivity.…”

Section: Discussionmentioning

confidence: 46%

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: 46%

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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“…Sixty-eight articles reported one or more patients with HSD17B3 mutations ( Supplemental Table S1 ) [ 1 , 3 , 4 , 5 , 9 , 10 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ...…”

Section: Resultsmentioning

confidence: 99%

Disorder of Sex Development Due to 17-Beta-Hydroxysteroid Dehydrogenase Type 3 Deficiency: A Case Report and Review of 70 Different HSD17B3 Mutations Reported in 239 Patients

Gonçalves

Carriço

Bastos

et al. 2022

IJMS

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The 17-beta-hydroxysteroid dehydrogenase type 3 (17-β-HSD3) enzyme converts androstenedione to testosterone and is encoded by the HSD17B3 gene. Homozygous or compound heterozygous HSD17B3 mutations block the synthesis of testosterone in the fetal testis, resulting in a Disorder of Sex Development (DSD). We describe a child raised as a female in whom the discovery of testes in the inguinal canals led to a genetic study by whole exome sequencing (WES) and to the identification of a compound heterozygous mutation of the HSD17B3 gene (c.608C>T, p.Ala203Val, and c.645A>T, p.Glu215Asp). Furthermore, we review all HSD17B3 mutations published so far in cases of 17-β-HSD3 deficiency. A total of 70 different HSD17B3 mutations have so far been reported in 239 patients from 187 families. A total of 118 families had homozygous mutations, 63 had compound heterozygous mutations and six had undetermined genotypes. Mutations occurred in all 11 exons and were missense (55%), splice-site (29%), small deletions and insertions (7%), nonsense (5%), and multiple exon deletions and duplications (2%). Several mutations were recurrent and missense mutations at codon 80 and the splice-site mutation c.277+4A>T each represented 17% of all mutated alleles. These findings may be useful to those involved in the clinical management and genetic diagnosis of this disorder.

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Novel mutations of the LHCGR gene in two families with 46,XY DSD causing Leydig cell hypoplasia I

et al. 2020

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Mutational Profile of 10 Afflicted Egyptian Families with 17-β-HSD-3 Deficiency

Cited by 4 publications

References 38 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

Disorder of Sex Development Due to 17-Beta-Hydroxysteroid Dehydrogenase Type 3 Deficiency: A Case Report and Review of 70 Different HSD17B3 Mutations Reported in 239 Patients

Novel mutations of the LHCGR gene in two families with 46,XY DSD causing Leydig cell hypoplasia I

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