Prenatal diagnosis of ATR-X syndrome in a fetus with a new G > T splicing mutation in the XNP/ATR-X gene

The molecular cause of the alpha -thalassemia/mental retardation syndrome ( ATR-X) resides in mutations affecting the XNP/ATR-X gene. Recently molecula r defects in the gene have been found in singular cases of a discrete numbe r of X-linked mental retardation (XLMR). ATR-X-affected males are character ised by severe mental retardation, distinct facial dysmorphisms and genital abnormalities, besides a wide spectrum of pathological features and an ext remely limited biological fitness. Given that molecular investigation of XN P/ATR-X mutations is made onerous by the length of the gene transcript, we carried out a prenatal diagnosis in a fetus at risk for ATR-X syndrome by i nitially determining the XNP/ATR-X gene haplotype before considering gene s equencing. Disease-associated haplotype analysis was performed selecting fi ve genic (CA)(n) repeats that showed high heterozygosity (Het > 0.7) in the general population. The fetus segregated an identical allelic pattern to t hat of the affected child of the family under investigation who shows featu res suggestive of the ATR-X syndrome. Subsequent mutational analysis of the gene revealed a novel IVS3+1G >T splicing mutation confirming the diagnosi s. Copyright (C) 2001 John Wiley & Sons, Ltd.