Novel cases of Tunisian patients with mutations in the gene encoding 17ß-hydroxysteroid dehydrogenase type 3 and a founder effect.
J Steroid Biochem Mol Biol
; 165(Pt A): 86-94, 2017 01.
Article
en En
| MEDLINE
| ID: mdl-26956191
17ß-Hydroxysteroid dehydrogenase type 3 (17ß-HSD3) is expressed almost exclusively in the testis and converts Δ4-androstene-3,17-dione to testosterone. Mutations in the HSD17B3 gene causing 17ß-HSD3 deficiency are responsible for a rare recessive form of 46, XY Disorders of Sex Development (46, XY DSD). We report novel cases of Tunisian patients with 17ß-HSD3 deficiency due to previously reported mutations, i.e. p.C206X and p.G133R, as well as a case with the novel compound heterozygous mutations p.C206X and p.Q176P. Moreover, the previously reported polymorphism p.G289S was identified in a heterozygous state in combination with a novel non-coding variant c.54G>T, also in a heterozygous state, in a male patient presenting with micropenis and low testosterone levels. The identification of four different mutations in a cohort of eight patients confirms the generally observed genetic heterogeneity of 17ß-HSD3 deficiency. Nevertheless, analysis of DNA from 272 randomly selected healthy controls from the same geographic area (region of Sfax) revealed a high carrier frequency for the p.C206X mutation of approximately 1 in 40. Genotype reconstruction of the affected pedigree members revealed that all p.C206X mutation carriers harbored the same haplotype, indicating inheritance of the mutation from a common ancestor. Thus, the identification of a founder effect and the elevated carrier frequency of the p.C206X mutation emphasize the importance to consider this mutation in the diagnosis and genetic counseling of affected 17ß-HSD3 deficiency pedigrees in Tunisia.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
17-Hidroxiesteroide Deshidrogenasas
Tipo de estudio:
Etiology_studies
/
Incidence_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Límite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
/
Humans
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Infant
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Male
/
Newborn
País/Región como asunto:
Africa
Idioma:
En
Revista:
J Steroid Biochem Mol Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2017
Tipo del documento:
Article
Pais de publicación:
Reino Unido