5α-Reductase 2 Gene Mutations in Three Unrelated Patients of Greek Cypriot Origin: Identification of an Ancestral Founder Effect

Skordis, Nicos; Patsalis, Philippos C.; Bacopoulou, Ioanna; Sismani, Carolina; Sultan, Charles; Lumbroso, Serge

doi:10.1515/jpem.2005.18.3.241

Cited by 22 publications

(16 citation statements)

References 8 publications

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“…Mutations in the SRD5A2 gene lead to a reduction in enzymatic activity and DHT production [6], causing defective masculinization in the forms of hypospadia and microphallus [7,8]. To date, more than 50 different mutations have been reported in patients with 5α-reductase type 2 deficiency, and missense and nonsense mutations were frequently reported [4,9,10,11,12,13]. …”

Section: Introductionmentioning

confidence: 99%

A Novel SRD5A2 Mutation with Loss of Function Identified in Chinese Patients with Hypospadias

et al. 2011

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Objective: To investigate the functional change of SRD5A2 gene mutations identified in patients with 5α-reductase type 2 deficiency. Patients and Methods: Three unrelated subjects born with ambiguous genitalia were included. All patients were initially reared as girls, but they gradually exhibited variable degrees of virilization at puberty without breast development, followed by a change of gender role. Sequencing analysis of the SRD5A2 gene was performed and enzymatic activities of 5α-reductase type 2 were assessed. Results: Three compound heterozygous mutations in the SRD5A2 gene were identified: patient 1 with p.G203S/ c.655delT, patient 2 with p.Q6X/p.G203S, and patient 3 with p.G203S/c.755_756insT. Heterozygosity for the p.V89L polymorphism was also found in patients 2 and 3. The c.655delT mutation led to a complete loss of the enzymatic activity, whereas mutants p.G203S and c.755_756insT resulted in a reduction of the enzymatic activities by 60 and 90%, respectively. Conclusion: Two frameshift heterozygous mutations, c.655delT and c.755_756insT, led to a dramatic reduction in 5α-reductase activity, and the latter had not been reported previously. In addition, the heterozygous mutation (p.G203) identified in the 3 patients presumably suggests a founder effect in the Chinese population and may explain the similarity in phenotype among the patients.

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Section: Introductionmentioning

confidence: 99%

A Novel SRD5A2 Mutation with Loss of Function Identified in Chinese Patients with Hypospadias

et al. 2011

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“…23 Identical splicemutations affecting the 5alpha-steroid reductase type 2 gene (SRD5A2) gene-5aSRD IVS1-2A>G-have been found in Cypriots which are most probably due to a founder effect. 24 In conclusion, we report here a Cypriot family with FNDI associated with a mutation within the AVP moiety of the AVP-NPII gene. This offers further confirmation that mutations affecting position 2 of AVP are causally implicated in autosomal dominant FNDI.…”

Section: Discussionmentioning

confidence: 65%

Identification of an AVP-NPII mutation within the AVP moiety in a family with neurohypophyseal diabetes insipidus: review of the literature

Koufaris¹,

Alexandrou²,

Sismani³

et al. 2015

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“…41 Our study in the general population indicates that this is a common mutation in the Cyprus population with an estimated carrier frequency of 0.98%. 7 This is further supported by the fact that this mutation has so far been reported at high frequency only in this geographic area.…”

Section: Discussionmentioning

confidence: 65%

Late diagnosis of 5alpha steroid-reductase deficiency due to IVS12A>G mutation of the SRD5a2 gene in an adolescent girl presented with primary amenorrhea

Skordis

Shammas

Efstathiou

et al. 2011

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The clinical spectrum of 5α-reductase deficiency, caused by mutations in the SRD5A2 gene, ranges from complete female appearance of the external genitalia at birth to nearly complete male phenotype. cAse rePOrt: A 14-year-old girl presented with primary amenorrhea (PA) and lack of breast development. she was 173 cm in height, had an increased amount of pubic hair and clitoromegaly (3 cm), with a 4 cm blind vaginal pouch. Gonads were palpable in the inguinal canal bilaterally and no uterus was identified on ultrasound. chromosomal analysis showed a 46,XY karyotype. the testosterone/DHt ratio was high (16.5) and further increased to 29.4 after stimulation with hcG, thus favouring the diagnosis of 5α-reductase deficiency. Since the issue of gender change was not considered, gonadectomy was performed followed by successful feminisation with hormonal replacement therapy. GeNetIc stUDIes: Molecular analysis of the SRD5A2 gene by DNA sequencing of all 5 exons revealed the presence of the splice mutation A>G at position -2 of the acceptor site of intron 1/exon 2 (Ivs1-2A>G) in homozygosity. both non-consanguineous parents were found to be heterozygotes for this mutation. cONcLUsIONs: Although rare, SRD5A2 gene defect should be suspected in any girl presenting with PA and virilisation at puberty. the Ivs1-2A>G mutation of the SRD5A2 gene predominates in Greek-Cypriot patients with 5α-reductase deficiency and very likely reflects a founder effect.

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5α-Reductase 2 Gene Mutations in Three Unrelated Patients of Greek Cypriot Origin: Identification of an Ancestral Founder Effect

Cited by 22 publications

References 8 publications

A Novel SRD5A2 Mutation with Loss of Function Identified in Chinese Patients with Hypospadias

A Novel SRD5A2 Mutation with Loss of Function Identified in Chinese Patients with Hypospadias

Identification of an AVP-NPII mutation within the AVP moiety in a family with neurohypophyseal diabetes insipidus: review of the literature

Late diagnosis of 5alpha steroid-reductase deficiency due to IVS12A>G mutation of the SRD5a2 gene in an adolescent girl presented with primary amenorrhea

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