Mutational analysis of rare subtypes of congenital adrenal hyperplasia in a highly inbred population

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:461

Article

Alswailem, Meshael M.¹  Alzahrani, Ohoud S.²  Alhomaidah, Doha S.²  Alasmari, Rahma²  Qasem, Ebtesam¹  Murugan, Avaniyapuram Kannan¹  Alsagheir, Afaf²  Brema, Imad⁴  Ben Abbas, Bassam²  Almehthel, Mohammed³  Almeqbali, Ali⁵  Alzahrani, Ali S.^1,3 

[1] King Faisal Specialist Hosp & Res Ctr, Dept Mol Oncol, Riyadh, Saudi Arabia

[2] King Faisal Specialist Hosp & Res Ctr, Dept Pediat, Riyadh, Saudi Arabia

[3] King Faisal Specialist Hosp & Res Ctr, Dept Med, Riyadh, Saudi Arabia

[4] King Fahad Med City, Dept Med, Riyadh, Saudi Arabia

[5] Natl Diabet & Endocrine Ctr, Muscat, Oman

关键词: Congenital adrenal hyperplasia;    Mutation;    Ambiguous genitalia;    Disorders of sex development;   

DOI  :  10.1016/j.mce.2017.08.022

来源: Elsevier

【 摘 要 】

Context: Apart from 21 Hydroxylase deficiency, other subtypes of congenital adrenal hyperplasia (CAH) are rare. We studied the clinical features and molecular genetics of a relatively large series of patients with CYP17A1, HSD3 beta 2 and StAR deficiencies. Patients and methods: We studied 21 patients including 7 patients with CYP17A1, 10 patients with HSD3 beta 2 and 4 patients with StAR deficiencies. For mutation detection, we isolated DNA from peripheral leucocytes, amplified genes of interest using polymerase chain reaction and directly sequenced the amplicons using Dideoxy Chain Termination method. Results: Regardless of their karyotype, patients with CYP17A1 deficiency presented with normally looking external female genitalia and were raised as females. Hypertension and hypokalemia were prominent features in 4 of 7 patients. Two missense (p.R416H, p.R239Q) and 2 non-sense (p.Y329X, p.Y329X) mutations were found in these 7 cases. In 3 unrelated families with 10 affected siblings with HSD3 beta 2 mutations, two non-sense mutations were found (p.Q334X, p.R335X). 46XY patients with HSD3 beta 2 deficiency presented with ambiguous genitalia while 46XX patients presented with normal female external genitalia. Adrenal crisis was common in patients with both karyotypes. In the 4 patients with StAR deficiency, both genetic male and female patients presented with normally looking female external genitalia and adrenal crisis. One previously reported missense mutation (p.R182H) was found in 3 unrelated patients and a novel non-sense mutation (p.Q264X) in the fourth patient. Conclusions: These cases of rare subtypes of CAH illustrate the heterogeneous phenotypic and genetic features of these subtypes and add unique novel mutations to the previously known ones. (C) 2017 Elsevier B.V. All rights reserved.

【 授权许可】

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