Shaikh Shagufta, Shettigar Suresh K G, Kumar Santosh, Kantharia Surita, Kurva Jagannath, Cherian Susan
Cytogenetics and Molecular Genetics Section, Pathology Unit, Bhabha Atomic Research Centre Hospital, Anushaktinagar, Mumbai 400 094, India.
J Genet. 2019 Mar;98.
This study evaluates a family with two siblings having severe growth retardation and facial dysmorphism, born to consanguineous normal healthy parents. Affymetrix CytoScan 750K microarray showed a 34-Mb pericentric homozygous region on chromosome 6 for both siblings. was one of the 141 genes present in this region. Sanger sequencing of gene detected a 2-bp novel deletion in the 15th exon (c.2943_2944delCT of the cDNA). This deletion leads to a frameshift and a premature termination signal much upstream of the wild-type termination signal, leading to a nonsense mediated decay of the mRNA. CUL7 protein plays an important role in formation of 3M complex, ubiquitination, microtubule dynamics and cell cycle regulation. Mutations in gene is known to cause a rare 3M syndrome. Information about the novel mutation has been accepted in the ClinVar database with rs1064792895.
本研究评估了一个家庭，该家庭中有两个患有严重生长发育迟缓及面部畸形的兄弟姐妹，他们的父母是近亲结婚的正常健康人。Affymetrix CytoScan 750K基因芯片显示，两个兄弟姐妹在6号染色体上均有一个34兆碱基的近着丝粒纯合区域。 是该区域存在的141个基因之一。对 基因进行Sanger测序，在第15外显子中检测到一个2碱基的新缺失（cDNA的c.2943_2944delCT）。这种缺失导致移码，并在野生型终止信号上游很远的位置产生一个过早的终止信号，从而导致mRNA的无义介导衰变。CUL7蛋白在3M复合物的形成、泛素化、微管动力学和细胞周期调控中起重要作用。已知 基因的突变会导致一种罕见的3M综合征。关于该新突变的信息已被ClinVar数据库收录，编号为rs1064792895。
