A new approach for molecular diagnosis of TAR syndrome

• Published in: Clinical biochemistry 2014-06, Vol.47 (9), p.835-839
• Main Authors: Yassaee, Vahid R., Hashemi-Gorji, Feyzollah, Soltani, Ziba, Poorhosseini, Seyed Mohammad
• Format: Article
• Language: English
• Subjects: Adult; Base Sequence; Case-Control Studies; Consanguinity; Fatal Outcome; Female; Humans; Infant, Newborn; Male; Molecular Diagnostic Techniques; Molecular Sequence Data; Pedigree; Polymorphism, Single Nucleotide; Quantitative real-time PCR; Radius; RBM8A; RBM8B; RNA-Binding Proteins - genetics; rs139428292; rs201779890; Sequence Analysis, DNA; TAR syndrome; Thrombocytopenia - diagnosis; Thrombocytopenia - genetics; Upper Extremity Deformities, Congenital - diagnosis; Upper Extremity Deformities, Congenital - genetics; Young Adult
• ISSN: 0009-9120; 1873-2933
• DOI: 10.1016/j.clinbiochem.2014.04.018

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. •Evaluation of a cost-effective molecular method for diagnosis of TAR is proposed.•Sanger sequencing and FISH may not proper for molecular diagnosis of TAR syndrome.•Homology of RBM8B pseudogene and RBM8A gene causes misinterpretation of result.•qPCR would be the most cost-effective method for molecular diagnosis of TAR.•Rare genetic syndrome may be undiagnosed because of unsuitable molecular approach.