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.
Genomic Research Center, Shahid Beheshti University of Medical Sciences, Taleghani Hospital, Tehran 1966645643, Iran; Dept. of Medical Genetic, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1966645643, Iran. Electronic address: v.yassaee-grc@sbmu.ac.ir.
Vahid R
VR
Yassaee
Genomic Research Center, Shahid Beheshti University of Medical Sciences, Taleghani Hospital, Tehran 1966645643, Iran.
Feyzollah
F
Hashemi-Gorji
Genomic Research Center, Shahid Beheshti University of Medical Sciences, Taleghani Hospital, Tehran 1966645643, Iran.
Ziba
Z
Soltani
Dept. of Medical Genetic, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1966645643, Iran.
Seyed Mohammad
SM
Poorhosseini
D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D000080984:Congenital Bone Marrow Failure Syndromes; D003241:Consanguinity; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D025202:Molecular Diagnostic Techniques; D008969:Molecular Sequence Data; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins / Q000235:genetics; D011884:Radius; D017422:Sequence Analysis, DNA; D013921:Thrombocytopenia / Q000175:diagnosis* / Q000235:genetics; D038062:Upper Extremity Deformities, Congenital / Q000175:diagnosis* / Q000235:genetics; D055815:Young Adult
C406243:RBM8A protein, human; D016601:RNA-Binding Proteins
Quantitative real-time PCR; RBM8A; RBM8B; TAR syndrome; rs139428292; rs201779890