Analysis of clinical characteristics and genetic variants in two pedigrees affected with Autosomal dominant intellectual developmental disorder 49
10.3760/cma.j.cn-511374-20240102-00002
- VernacularTitle:常染色体显性智力障碍49型2个家系的临床表型与基因变异分析
- Author:
Yuqiang LYU
1
;
Yanqing ZHANG
;
Ning LI
;
Kaihui ZHANG
;
Min GAO
;
Jian MA
;
Weitong GUO
;
Yi LIU
;
Zhongtao GAI
Author Information
1. 山东大学附属儿童医院（济南市儿童医院）儿科研究所，济南 250022
- Keywords:
Intellectual disability;
Autosomal dominant intellectual developmental disorder 49;
TRIP12 gene;
High-throughput sequencing
- From:
Chinese Journal of Medical Genetics
2024;41(11):1296-1301
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical and genetic features of two Chinese pedigrees affected with Autosomal dominant intellectual developmental disorder 49 (MRD49).Methods:Two MRD49 pedigrees which were admitted to the Children′s Hospital Affiliated to Shandong University respectively on January 28, 2021 and November 10, 2022 were selected as the study subjects. Clinical data of the two pedigrees were collected and analyzed. Genomic DNA was extracted from peripheral blood samples of the probands and their family members. The probands were subjected to mutational analysis by high-throughput sequencing. Candidate variants were validated using real-time fluorescence quantitative PCR (q-PCR) or Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Shandong University (No. SDFE-IRB/T-2022002).Results:Proband 1 had presented with language delay, motor retardation and intellectual disability, and his maternal grandmother, mother, aunt and cousin all had various degrees of intellectual disability. Sequencing results showed that proband 1 had deletion of exons 3 ~ 7 of the TRIP12 gene. q-PCR verification showed that his mother, aunt, maternal grandmother and cousin had all harbored the same deletion. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP1). Proband 2, who had mainly presented with language delay, motor retardation and intellectual disability, and was found to harbor a heterozygous c.3010C>T (p.Arg1004*) variant of the TRIP12 gene, which was verified to be de novo in origin. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion:This study had diagnosed two MRD49 families through high-throughput sequencing. Above findings have enriched the phenotypic and mutational spectrum of MRD49 in China, which has also facilitated genetic counseling for the two pedigrees.
