Lin Li, Shen Fei, Yang Qi, Yi Shang, Qin Zailong, Zhang Qiang, Luo Jingsi, Gao Xiaoyan, He Sheng
Laboratory of Genetics and Metabolism, Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region, Birth Defects Prevention and Control Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530033, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2021 Jul 10;38(7):635-638. doi: 10.3760/cma.j.cn511374-20200520-00358.
To explore the genetic basis of four children with congenital hyperinsulinemia (CHI).
The four children were subjected to high-throughput whole exome sequencing (WES). Candidate variants were validated by Sanger sequencing.
WES analysis has identified 4 variants in the ABCC8 gene and 1 variant in GLUD1, including a ABCC8 c.382G>A variant in case 1, compound heterozygous c.698T>C and c.4213G>A variants of the ABCC8 gene concomitant with a de novo 14.9 Mb microduplication of chromosome 15 in case 2, and ABCC8 c.331G>A variant in case 3, and de novo c.955T>C variant of the GLUD1 gene in case 4. Of these, c.698T>C of the ABCC8 gene and c.955T>C of the GLUD1 gene were unreported previously. Based on the American College of Medical Genetics and Genomics guidelines, the c.382G>A(p.Glu128Lys), c.698T>C(p.Met233Thr) and c.4213G>A(p.Asp1405Asn) variants of ABCC8 gene and c.955T>C(p.Tyr319His) variant of GLUD1 gene were predicted to be likely pathogenic(PM1+PM2+PP3+PP4, PM1+PM2+PM5+PP3+PP4, PM1+PM2+PP3+PP4 and PS1+PM1+PM2+PP3), and the c.331G>A (p.Gly111Arg) variant of ABCC8 gene was predicted to be uncertain significance(PM1+PM2+PP4).
The variants of the ABCC8 and GLUD1 genes probably underlay the pathogenesis of CHI in the four patients. Above results have facilitated clinical diagnosis and genetic counseling for the affected families.
