Next Generation Sequencing-Based Molecular Diagnosis for Suspected Proband of Pseudoachondroplasia

【作者】 罗怀超； 杨季云； 林婴； 杨正林；

【机构】 四川省人民医院一四川省人类疾病基因研究重点实验室；

【摘要】 Pseudoachondroplasia（PSACH）is a rare and severe genetic disease;therefore,an accurate molecular diagnosis is essential for appropriate disease treatment and family planning.However,currently the diagnosis of PSACH mainly is based on family history,physical examination,and radiographic evaluation.Genetic studies of patients with PSACH in Chinese have been very limited.With the application of next-generation sequencing（NGS）,comprehensive molecular diagnosis of PSACH is now possible.The purpose of this study was to perform the NGS-based comprehensive molecular diagnosis for patients with PSACH in Chinese.We investigated the molecular genetics of one suspected PSACH family in this study.The DNA sample from proband was sequenced using custom capture panel,which includes 249 bone disease genes.Variants werecalled,filtered,and annotated by in-house automatic pipeline.Then,we confirmed the variants by Sanger sequence in three family members.After cosegregation analysis,the variant,c.1159₁161del of COMP gene is a novel mutation responsible for this familial PSACH.更多还原

【Abstract】 Pseudoachondroplasia（PSACH） is a rare and severe genetic disease;therefore,an accurate molecular diagnosis is essential for appropriate disease treatment and family planning.However,currently the diagnosis of PSACH mainly is based on family history,physical examination,and radiographic evaluation.Genetic studies of patients with PSACH in Chinese have been very limited.With the application of next-generation sequencing（NGS）,comprehensive molecular diagnosis of PSACH is now possible.The purpose of this study was to perform the NGS-based comprehensive molecular diagnosis for patients with PSACH in Chinese.We investigated the molecular genetics of one suspected PSACH family in this study.The DNA sample from proband was sequenced using custom capture panel,which includes 249 bone disease genes.Variants were called,filtered,and annotated by in-house automatic pipeline.Then,we confirmed the variants by Sanger sequence in three family members.After cosegregation analysis,the variant,c.1159₁161del of COMP gene is a novel mutation responsible for this familial PSACH.更多还原