PRKAR1A基因突变导致肢端发育不全1型4例分析

Analysis of 4 cases of acrodysostosis type 1 caused by PRKAR1A gene mutation

目的探讨4例由PRKAR1A基因突变导致的肢端发育不全1型患儿的临床表现和实验室检测结果。方法收集4例肢端发育不全1型患儿的临床资料和实验室检测结果,同时进行全外显子高通量测序,以临床表型为主要突变过滤依据,采用Sanger测序验证突变来源,根据《遗传变异分类标准与指南》进行变异致病性分类。结果4例肢端发育不全1型患儿的主要临床表现为身材矮小(-3s~-6s)、低体质量(-2s~-4s)、短指、特殊面容及多激素抵抗等,但不同患儿的临床表现有一定差异,部分患儿存在生长激素部分缺乏。4例患儿均检出PRKAR1A基因突变,其中3例患儿为同一突变c.1102C>T/p.Arg368^(*),1例患儿为c.1118A>G/p.Tyr373Cys,均为致病性变异。结论检出PRKAR1A基因的2个新发突变,由此导致的肢端发育不全1型患儿的临床表现存在异质性。

Objective To study 4 cases of acrodysostosis 1 caused by PRKAR1A gene mutation based on their clinical manifestations and laboratory parameters.Methods Clinical data and laboratory testing results of 4 cases of acrodysostosis 1 were collected,and whole exome high-throughput sequencing was performed.Phenotype-driven variant filters were performed to identify candidate variants,and Sanger sequencing was used to verify the parental origin of the variants.The pathogenicity of genetic variation was classified according to Standards and Guidelines for the Interpretation of Sequence Variants.Results The main clinical manifestations of the 4 cases were short stature(-3s--6s),low weight(-2s--4s),brachydactyly,dysmorphic facial features and multi-hormone resistance.Different clinical manifestations were observed among individuals,and some patients had partial growth hormone deficiency.Pathogenic mutations in PRKAR1A were detected in the 4 cases.Of them,3 cases had the mutation c.1102C>T/p.Arg368^(*),and the one had the mutation c.1118A>G/p.Tyr373Cys.Conclusion Totally,2 new mutations in PRKAR1A have been detected,and there is heterogeneity in the clinical manifestations of patients with acrodysostosis 1.