非偏态X染色体失活可能导致X连锁α地中海贫血/智力发育迟缓综合征（ATR-X）女性携带者出现智力发育迟缓：9名ATR-X女性携带者的X染色体失活研究

Non-skewed X-inactivation may cause mental retardation in a female carrier of X-linked alpha-thalassemia/mental retardation syndrome (ATR-X): X-inactivation study of nine female carriers of ATR-X.

作者信息

Wada Takahito, Sugie Hideo, Fukushima Yoshimitsu, Saitoh Shinji

机构信息

Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.

出版信息

Am J Med Genet A. 2005 Sep 15;138(1):18-20. doi: 10.1002/ajmg.a.30901.

DOI:10.1002/ajmg.a.30901

PMID:16100724

Abstract

X-linked alpha-thalassemia/mental retardation syndrome (ATR-X) is a syndromic form of X-linked mental retardation. We investigated the X-inactivation status of nine female ATR-X carriers by methylation-specific PCR of the HUMARA gene. Six carriers demonstrated a skewed X-inactivation pattern (>90:10) and one showed a non-skewed pattern (72:28), while two were uninformative because of homozygosity for the CAG repeat polymorphic alleles in the HUMARA. Only the carrier mother who showed non-skewed X-inactivation had moderate mental retardation. These findings suggest that mutations in ATRX may cause mental retardation in females, if the X chromosome carrying mutated ATRX is not properly inactivated.

摘要

X连锁α地中海贫血/智力发育迟缓综合征（ATR-X）是一种X连锁智力发育迟缓的综合征形式。我们通过对HUMARA基因进行甲基化特异性PCR，研究了9名女性ATR-X携带者的X染色体失活状态。6名携带者表现出偏态X染色体失活模式（>90:10），1名表现出非偏态模式（72:28），而2名由于HUMARA中CAG重复多态性等位基因纯合而无法提供有效信息。只有表现出非偏态X染色体失活的携带者母亲有中度智力发育迟缓。这些发现表明，如果携带突变型ATRX的X染色体未正确失活，ATRX突变可能导致女性智力发育迟缓。