Uniparental disomy of chromosome 8 leading to homozygosity of a CYP11B1 mutation in a patient with congenital adrenal hyperplasia: Implication for a rare etiology of an autosomal recessive disorder

Endocrine Journal

Noriyuki Katsumata¹  Satoko Ogita²  Naoki Kataoka²  Keiko Matsubara¹  Shinichiro Sano¹  Tsutomu Ogata¹  Maki Fukami¹ 

[1] Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan;Department of Pediatrics, Kawasaki Medical School, Kurashiki 701-0114, Japan

关键词: Autosomal recessive disorder;    Congenital adrenal hyperplasia;    CYP11B1;    Mutation;    Uniparental disomy;   

DOI  :  10.1507/endocrj.EJ13-0509

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(11)Cited-By(3)Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder that usually results from paternally and maternally transmitted mutations in genes for steroidogenic enzymes.Recent studies on steroid 21-hydroxylase deficiency, the most common form of CAH, have revealed that a small percentage of patients have a non-carrier parent; uniparental disomy (UPD) and de novo mutations were reported as disease-causing mechanisms in these patients.However, it remains unknown whether UPD and de novo mutations underlie other forms of CAH.Here, we report a male patient with steroid 11β-hydroxylase deficiency (11OHD) born to a non-carrier mother.The patient was identified by an elevated 17-hydroxyprogesterone level at a neonatal mass-screening test.His clinical features were comparable to those of previously reported patients with 11OHD.Direct sequencing of CYP11B1 identified a homozygous IVS7+1G>A mutation in the patient, which was not shared by his mother.Comparative genomic hybridization of the patient detected UPD of chromosome 8 [UPD(8)].Microsatellite analysis indicated non-maternal origin of the UPD(8) and confirmed parentage of other chromosomes.This study shows for the first time that 11OHD can be caused by UPD in the presence of a non-carrier parent.Awareness of such rare cases should improve the accuracy of genetic counseling for families with CAH.Our data support the importance of UPD as an underlying mechanism of autosomal recessive disorders.

【 授权许可】

Unknown