46,XY Disorder of Sex Development in a Sudanese Patient Caused by a Novel Mutation in the &lt;b&gt;&lt;i&gt;HSD17B3&lt;/i&gt;&lt;/b&gt; Gene

Ellaithi, Mona; Werner, Ralf; Riepe, Felix G.; Krone, Nils; Kulle, Alexandra; Diab, Tayseer; Kamel, Alaa K.; Arlt, Wiebke; Holterhus, Paul‐Martin; Sabir, Omyma; Hiort, Olaf

doi:10.1159/000363201

Cited by 8 publications

(4 citation statements)

References 29 publications

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“…19,20 17-β-HSD3 deficiency is a genetic steroid disorder of testicular androgen synthesis that was first described by Saez et al 21 As in our case, male newborns with 17-β-HSD3 deficiency usually have external genitalia with feminizing features together with undescended testes usually in the inguinal region or in a bifid scrotum. 5,10,11 The presence of Wolffian duct structures such as epididymis, seminal vesicles, vas deferens, and ejaculatory ducts may be explained by the low testosterone concentration, which appears to be sufficient for their development in utero.…”

Section: Discussionsupporting

confidence: 52%

“…23 However, almost all diagnosed cases of Arab patients involve male social sex assignment. 15,17,19,[23][24][25][26][27] The excessive virilization at puberty and its discrepancy from intrauterine masculinization is not fully understood, but it is thought to occur by one of two mechanisms. The first is attributed to the peripheral conversion of androstenedione to testosterone by other 17-β-HSD isoenzymes particularly isoenzyme five in extragonadal tissues.…”

Section: Discussionmentioning

confidence: 99%

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A Novel Mutation Causing 17-β-Hydroxysteroid Dehydrogenase Type 3 Deficiency in an Omani Child: First Case Report and Review of Literature

Al-Sinani¹,

Mula-Abed²,

Al-Kindi³

et al. 2015

Oman Med J

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This is the first case report in Oman and the Gulf region of a 17-β-hydroxysteroid dehydrogenase type 3 (17-β-HSD3) deficiency with a novel mutation in the HSD17B3 gene that has not been previously described in the medical literature. An Omani child was diagnosed with 17-β-HSD3 deficiency and was followed up for 11 years at the Pediatric Endocrinology Clinic, Royal Hospital, Oman. He presented at the age of six weeks with ambiguous genitalia, stretched penile and bilateral undescended testes. Ultrasound showed no evidence of any uterine or ovarian structures with oval shaped solid structures in both inguinal regions that were confirmed by histology to be testicular tissues with immature seminiferous tubules only. The diagnosis was made by demonstrating low serum testosterone and high androstenedione, estrone, and androstenedione:testosterone ratio. Karyotyping confirmed 46,XY and the infant was raised as male. Testosterone injections (25mg once monthly) were given at two and six months and then three months before his surgeries at five and seven years of age when he underwent multiple operations for orchidopexy and hypospadias correction. At the age of 10 years he developed bilateral gynecomastia (stage 4). Laboratory investigations showed raised follicle-stimulating hormone, luteinizing hormone, androstenedione, and estrone with low-normal testosterone and low androstendiol glucurunide. Testosterone injections (50mg once monthly for six months) were given that resulted in significant reduction in his gynecomastia. Molecular analysis revealed a previously unreported homozygous variant in exon eight of the HSD17B3 gene (NM_000197.1:c.576G>A.Trp192*). This variant creates a premature stop codon, which is very likely to result in a truncated protein or loss of protein production. This is the first report in the medical literature of this novel HSD17B3 gene mutation. A literature review was conducted to identify the previous studies related to this disorder.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

A Novel Mutation Causing 17-β-Hydroxysteroid Dehydrogenase Type 3 Deficiency in an Omani Child: First Case Report and Review of Literature

Al-Sinani¹,

Mula-Abed²,

Al-Kindi³

et al. 2015

Oman Med J

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show abstract

“…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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“…Also, a large duplication spanning from intron 2 to intron 10 was reported twice, both in a heterozygous pattern [Neocleous et al, 2012;Massanyi et al, 2013]. Only 9 coding exons (excluding exons 4 and 7) and 4 introns (introns 3, 6, 7 and 8) of the gene had reported missense or splice site mutations [George et al, 2010;Hassan et al, 2013;Ellaithi et al, 2014;Demir et al, 2015].…”

Section: Discussionmentioning

confidence: 99%

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

Hassan

Mazen²,

Gad³

et al. 2016

Sex Dev

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This study aimed at the detection of HSD17B3 gene mutations in Egyptian patients with suspected diagnosis of 46,XY DSD due to 17-β-HSD-3 deficiency and at evaluation of phenotype/genotype relationship of these mutations. The study was conducted on 11 patients of 10 families which were provisionally diagnosed to have 17-β-HSD-3 enzyme deficiency. Karyotyping, hormonal evaluation of testosterone, Δ4-androstenedione, and dihydrotestosterone, and sequencing analysis of the 11 exons of the HSD17B3 gene were done. Mutations in HSD17B3 were detected in exons 2, 7, 8, 10, and 11, and 6 novel mutations were determined in exons 1, 2, 7, and 8. Two patients showed compound heterozygous mutations, while 8 families had probands with homozygous mutations. The current study shows that 17-β-HSD-3 deficiency is not an uncommon disorder among Egyptian DSD cases. It was evidenced that the mutational profile of the disease is rather heterogeneous, relatively different from those reported in other populations, and has a high degree of novel genetic defects.

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46,XY Disorder of Sex Development in a Sudanese Patient Caused by a Novel Mutation in the <b><i>HSD17B3</i></b> Gene

Cited by 8 publications

References 29 publications

A Novel Mutation Causing 17-β-Hydroxysteroid Dehydrogenase Type 3 Deficiency in an Omani Child: First Case Report and Review of Literature

A Novel Mutation Causing 17-β-Hydroxysteroid Dehydrogenase Type 3 Deficiency in an Omani Child: First Case Report and Review of Literature

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

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

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