Wada Takahito, Sakakibara Masae, Fukushima Yoshimitsu, Saitoh Shinji
Department of Medical Genetics, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan.
Brain Dev. 2006 Jun;28(5):322-5. doi: 10.1016/j.braindev.2005.09.005. Epub 2006 Jan 10.
X-linked alpha-thalassemia/mental retardation syndrome (ATR-X, MIM#301040) is an X-linked recessive condition affecting males. ATR-X is characterized by severe mental retardation, mild HbH disease, dysmorphic facies, and genital and skeletal abnormalities. ATR-X is caused by mutations in the ATRX gene. Most mutations affect two functionally important domains, the ADD domain and the helicase domain. Here, we report on two brothers with the ATR-X phenotype without HbH disease; both had a mutation in the 5' upstream region of the ADD domain of the ATRX gene. This mutation was a G to T nucleotide substitution at the 3' end of exon 5 and resulted in splicing out of exons 5 and 6. Analysis of cDNA structure may clarify genotype-phenotype correlations in ATR-X because splicing mutation could be detectable only by cDNA analysis.
X连锁α地中海贫血/智力发育迟缓综合征（ATR-X，MIM#301040）是一种影响男性的X连锁隐性疾病。ATR-X的特征是严重智力发育迟缓、轻度HbH病、面容畸形以及生殖器和骨骼异常。ATR-X由ATRX基因突变引起。大多数突变影响两个功能重要的结构域，即ADD结构域和解旋酶结构域。在此，我们报告了两名患有ATR-X表型但无HbH病的兄弟；两人在ATRX基因ADD结构域的5'上游区域均有突变。该突变是外显子5 3'端的G到T核苷酸替换，导致外显子5和6缺失。cDNA结构分析可能会阐明ATR-X中的基因型-表型相关性，因为剪接突变只能通过cDNA分析检测到。
