Three novel TBX5 mutations in Chinese patients with Holt-Oram syndrome

Holt-Gram syndrome (HOS) is an autosomal dominant syndrome that comprises u pper limb and cardiac defects. The gene responsible for HOS, TBX5, was isol ated and many mutations have been identified in HOS patients. We analyzed 1 1 Chinese HOS patients (7 from three families and 4 sporadic cases) for TBX 5 mutation by single strand conformation polymorphisms (SSCPs), Three SSCP changes were detected in two of the three familial cases and one sporadic c ase. Sequence analysis identified three novel, heterozygous mutations in TB X5: a frameshift mutation caused by one base deletion [C416del] in one fami ly, a mis-sense mutation (Gln49Lys) induced by a base substitution (C145A) in another family, and the other mis-sense mutation (Ile54Thr) by T161C in one sporadic case. The patients with the frameshift mutations had severer c linical manifestations that involved aplasia/hypoplasia of the arm and thum bs, while those with the mis-sense mutations presented with milder anomalie s such as absent or hypoplastic thumbs but without arm abnormalities. These observations may support a genotype-phenotype correlation in HOS patients with TBX5 mutation. Am. J, Med, Genet, 92:237-240, 2000, (C) 2000 Wiley-Lis s, Inc.