Clinical and molecular spectrum of patients with 17β-hydroxysteroid dehydrogenase type 3 (17-β-HSD3) deficiency

Castro, Carla Cristina Telles de Sousa; Guaragna‐Filho, Guilherme; Calais, Flávia Leme de; Coeli, Fernanda Borchers; Leal, Ianik Rafaela Lima; Cavalcante-Junior, Erisvaldo Ferreira; Monlleó, Isabella Lopes; Pereira, Silma Regina Ferreira; Silva, Roberto Benedito de Paiva e; Gabiatti, José Roberto Erbolato; Marques-de-Faria, Antônia Paula; Maciel‐Guerra, Andréa Trevas; Mello, Maricilda Palandi de; Guerra‐Júnior, Gil

doi:10.1590/s0004-27302012000800012

Cited by 30 publications

(12 citation statements)

References 26 publications

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“…Collectively, the phenotype of the external genitalia indicated moderately defective masculinization, where 2 patients had Quigley score 3 and the other had score 4. This genital ambiguity might be the cause for their early presentations in infancy or early childhood, which is a finding similar to the 3 previously reported cases [Boehmer et al, 1999;Bertelloni et al, 2009;Castro et al, 2012]. The second recurrent mutation in our study was c.575A>C (p.Gln176Pro) in exon 8.…”

Section: Discussionsupporting

confidence: 90%

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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Section: Discussionsupporting

confidence: 90%

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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“…HSD17B3 deficiency is an autosomal recessive disorder characterised by ambiguous genitalia and significant virilisation during puberty due to conversion of androstenedine to testosterone by extra-gonadal HSD17B isoenzymes or residual HSD17B3 activity ( 25 ). Puberty-dependent virilization pushes many patients to change their social sex to male at puberty.…”

Section: Discussionmentioning

confidence: 99%

Disorders of sex development: a study of 194 cases

Walia

Singla

Vaiphei

et al. 2018

Endocrine Connections

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ObjectiveTo study the clinical proﬁle and the management of patients with disorders of sex development (DSD).Design and settingRetrospective study from a tertiary care hospital of North India.Methods and patientsOne hundred ninety-four patients of DSD registered in the Endocrine clinic of Postgraduate Institute of Medical Education and Research, Chandigarh between 1995 and 2014 were included.ResultsOne hundred and two patients (52.5%) had 46,XY DSD and seventy-four patients (38.1%) had 46,XX DSD. Sex chromosome DSD was identified in seven (3.6%) patients. Of 102 patients with 46,XY DSD, 32 (31.4%) had androgen insensitivity syndrome and 26 (25.5%) had androgen biosynthetic defect. Of the 74 patients with 46,XX DSD, 52 (70.27%) had congenital adrenal hyperplasia (CAH) and eight (10.8%) had ovotesticular DSD. Five patients with sex chromosome DSD had mixed gonadal dysgenesis. Excluding CAH, majority of the patients (90%) presented in the post-pubertal period. One-fourth of the patients with simple virilising CAH were reared as males because of strong male gender identity and behaviour and firm insistence by the parents. Corrective surgeries were performed in twenty patients (20%) of 46,XY DSD without hormonal evaluation prior to the presentation.ConclusionCongenital adrenal hyperplasia is the most common DSD in the present series. Most common XY DSD is androgen insensitivity syndrome, while CAH is the most common XX DSD. Delayed diagnosis is a common feature, and corrective surgeries are performed without seeking a definite diagnosis.

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“…The c.277 + 2 T > G HSD17B3 mutation located in the 5′ splice site of intron 3 (Fig. 1 ) was previously described in compound heterozygosis with the c.277 + 4 A > T mutation in a 46,XY female patient 23 . As aberrant splicing had already been described for the c.277 + 4 A > T HSD17B3 mutation 19 , we investigated the affect of the c.277 + 2 T > G mutation on splicing.…”

Section: Resultsmentioning

confidence: 70%

A study of splicing mutations in disorders of sex development

Calais

Smith

Raponi

et al. 2017

Sci Rep

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The presence of splicing sequence variants in genes responsible for sex development in humans may compromise correct biosynthesis of proteins involved in the normal development of gonads and external genitalia. In a cohort of Brazilian patients, we identified mutations in HSD17B3 and SRD5A2 which are both required for human sexual differentiation. A number of these mutations occurred within regions potentially critical for splicing regulation. Minigenes were used to validate the functional effect of mutations in both genes. We evaluated the c.277 + 2 T > G mutation in HSD17B3, and the c.544 G > A, c.548-44 T > G and c.278delG mutations in SRD5A2. We demonstrated that these mutations altered the splicing pattern of these genes. In a genomic era these results illustrate, and remind us, that sequence variants within exon-intron boundaries, which are primarily identified for diagnostic purposes and have unknown pathogenicity, need to be assessed with regards to their impact not only on protein expression, but also on mRNA splicing.

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Clinical and molecular spectrum of patients with 17β-hydroxysteroid dehydrogenase type 3 (17-β-HSD3) deficiency

Cited by 30 publications

References 26 publications

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

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

Disorders of sex development: a study of 194 cases

A study of splicing mutations in disorders of sex development

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