A splicing mutation affecting expression of ataxia–telangiectasia and Rad3–related protein (ATR) results in Seckel syndrome

摘要: Seckel syndrome (OMIM 210600) is an autosomal recessive disorder characterized by intrauterine growth retardation, dwarfism, microcephaly and mental retardation. Clinically, shares features in common with disorders involving impaired DNA-damage responses, such as Nijmegen breakage 251260) LIG4 606593). We previously mapped a locus associated to chromosome 3q22.1–q24 two consanguineous Pakistani families1. Further marker analysis the families, including recently born unaffected child recombination critical region, narrowed region interval of 5 Mbp between markers D3S1316 D3S1557 (145.29 150.37 Mbp). The gene encoding ataxia–telangiectasia Rad3–related protein (ATR) maps this region2,3. A fibroblast cell line derived from affected individual displays defective DNA damage response caused ATR function. identified synonymous mutation individuals that alters splicing. confers phenotype marked (head circumference 12 s.d. below mean) dwarfism (5 mean). Our shows UV-induced activation can occur non-replicating cells following processing nucleotide excision repair.