CLINICAL CLASSIFICATION OF RADIAL RAY DEFECTS AND RESEARCH INTO ETIOPATHOGENESIS

DOI: 10.26650/IUITFD.427250 Objective: Radial ray defects (RRDs) are the most common congenital abnormality of the upper extremities, with a prevalence of 1:30,000. 70% of RRDs are syndromic or accompanied by additional malformations, whereas 30% are in isolated form. Definitive diagnosis is critical for follow-up and provides an opportunity for prenatal diagnosis. The aim of this study was to provide a guide for the differential diagnosis of patients with RRD via contributing to their molecular diagnosis by constructing a next-generation sequencing (NGS) gene-panel test. Materials and Methods: 48 probands from 37 families, referred for genetic consultation due to RRD, between the years of 2004–2014, were evaluated by cytogenetic and molecular tools following clinical examinations. 31 probands, with normal karyotype, were screened for 43 RRD associated genes of 14 syndromes by using in-house-designed targeted NGS gene-panel. Results: Chromosomal abnormalities [a trisomy 18 and a familial reciprocal translocation t(2;12)(q31;q24.3)] in two families and mutations in related genes (SF3B4, SALL4, TBX5, FANCA) in four families were known before the initiation of this study. In remaining 31 probands, five families identified to have six different mutations in four different genes (FANCA, NIPBL, ESCO2, BRIP1). Conclusion: Chromosomal abnormalities in two of the 37 families (5.4%) and gene mutations in nine of the 37 families (24.3%) were identified. Our study demonstrated that an in-house-designed targeted NGS containing 43 genes made considerable contribution to the diagnosis of RRD. Moreover, chromosomal abnormalities must always be considered in the differential diagnosis and excluded before gene-panel screening