ATR基因变异致兄弟同患塞克尔综合征1型

Siblings Seckel’s syndrome 1 caused by ATR gene variants in a sibpair

目的对来自同一家系的两例塞克尔综合征1型患儿进行基因型与表型分析。方法收集患儿的临床资料,提取外周血进行全外显子与Sanger测序对患儿进行变异分析,通过文献复习了解本病的临床特征。结果患儿系足月小样儿,生长迟缓、发育落后、小头畸形、鸟头样面容。基因检测结果显示其ATR基因c.1A>G(p.M1?)和c.4853-18A>G复合杂合变异,分别来自患儿父母。两个变异均未见文献报道。结论c.1A>G(p.M1?)和c.4853-18A>G复合杂合变异可能是患儿的致病原因,两个新变异的检出丰富了ATR基因的变异谱。

Objective Two brothes with Seckel’s syndrome 1(SCKL1)were reported and a literature review was carried to provide clinical and genetic information of this rare disease.Methods Clinical data of the two children were collected,and the peripheral blood was extracted for whole exome sequencing.Literature of the disease were reviewed.Results The two patients were 11 years and 9.5 years old when examined for short stature.They presented with intrauterine growth retardation,intellectual disability,microcephaly,birdhead-like face and coffee au lait spots.The bone age was more than 2 years behind the chronical age and the growth hormone levels were normal.Whole exome sequencing revealed novel compound heterozygous variants c.1A>G(P.M1?)and c.4853-18A>G of ART gene in both children.Conclusion Children with prenatal onset short stature,developmental delay,microcephaly and special facial featuresshould be considered for the possibility of Seckel’s syndrome,whole exome sequencing could help to confirm the clinical diagnosis.