A new approach for molecular diagnosis of TAR syndrome.

Thrombocytopenia-absent radius (TAR) syndrome is a rare genetic disorder inherited in an autosomal recessive fashion. In most patients chromosomes at 1q21.1 harbor a 200-kb deletion consisted of many genes, including RBM8A. We aimed to examine a cost-effective method for investigation a consanguineous family clinically diagnosed as TAR syndrome. A comprehensive sequencing of RBM8A identified several SNPs including two low-frequency regulatory SNPs (rs139428292 and rs201779890) in the father, the mother and the proband in which they carried A/G, G/- and A/- alleles for rs139428292, respectively. They also had G/G genotype in the father, G/- in both mother and proband for rs201779890. In addition a SNP (rs872786) was found in mother as T/- allele while father and proband have possessed A/A and A/- alleles, respectively. Further investigation determined a rare null allele in the proband using quantitative real-time PCR. We concluded that compound inheritance of a rare null allele and one of the two low-frequency noncoding SNPs (rs139428292) in RBM8A are crucial for TAR syndrome. Quantitative real-time PCR and Sanger sequencing may recruit for molecular diagnosis of TAR rather than molecular cytogenetic study.