Kleinle S, Lang R, Fischer G F, Vierhapper H, Waldhauser F, Födinger M, Baumgartner-Parzer S M
Department of Internal Medicine III, Division of Clinical Endocrinology and Metabolism, Medical University of Vienna, A-1090 Vienna, Austria.
J Clin Endocrinol Metab. 2009 Oct;94(10):3954-8. doi: 10.1210/jc.2009-0487. Epub 2009 Sep 22.
Rare haplotypes with Q318X mutations and duplicated CYP21A2 genes have been reported to occur in different populations to a varying extent. Discrimination between a normal (Q318X mutation on one of the duplicated CYP21A2 genes) and a congenital adrenal hyperplasia (CAH, Q318X mutation without duplicated functional gene) allele is of importance, particularly for prenatal diagnosis and the respective genetic counseling. Although methods to differentiate between such alleles have been published only recently, it remains unclear with which frequency Q318X mutations are associated with duplicated CYP21A2 genes and whether these haplotypes have a common ancestry.
Human leukocyte antigen (HLA) typing has been performed in 38 unrelated individuals and in 11 family members detected to carry a Q318X mutation in the course of CYP21 genotyping using sequence, multiplex ligation-dependent probe amplification, and Southern blot analyses.
The majority (n = 32, 84.2%) of the 38 unrelated individuals carrying the Q318X mutation had the trimodular RCCX haplotype, carrying the Q318X mutation on a duplicated CYP21A2 gene. Twenty-two individuals of these 32 (68.8%) were of the rare HLA-B50-Cw06 haplotype, suggesting a common ancestry of this haplotype. In five (13.2%) of the 38 subjects, the Q318X mutation was not associated with a duplicated CYP21A2 gene and thus represents a CAH allele. None of these five patients had the above mentioned HLA haplotype.
The majority of individuals in whom Q318X mutations are detected carry a duplicated functional CYP21A2 gene and the rare HLA-B50-Cw06 haplotype.
据报道，携带Q318X突变和CYP21A2基因重复的罕见单倍型在不同人群中的出现程度各不相同。区分正常（重复的CYP21A2基因之一上存在Q318X突变）和先天性肾上腺皮质增生（CAH，无重复功能基因的Q318X突变）等位基因至关重要，特别是对于产前诊断和相应的遗传咨询。尽管区分此类等位基因的方法直到最近才公布，但尚不清楚Q318X突变与重复的CYP21A2基因相关的频率，以及这些单倍型是否有共同的祖先。
对38名无亲缘关系的个体以及在CYP21基因分型过程中检测到携带Q318X突变的11名家庭成员进行了人类白细胞抗原（HLA）分型，采用序列分析、多重连接依赖探针扩增和Southern印迹分析。
38名携带Q318X突变的无亲缘关系个体中，大多数（n = 32，84.2%）具有三联体RCCX单倍型，在重复的CYP21A2基因上携带Q318X突变。这32名个体中有22名（68.8%）具有罕见的HLA - B50 - Cw06单倍型，表明该单倍型有共同的祖先。在38名受试者中的5名（13.2%）中，Q318X突变与重复的CYP21A2基因无关，因此代表CAH等位基因。这5名患者均无上述HLA单倍型。
检测到Q318X突变的个体中，大多数携带重复的功能性CYP21A2基因和罕见的HLA - B50 - Cw06单倍型。
