Open AccessUncovering the molecular pathogenesis of congenital hyperinsulinism by panel gene sequencing in 32 Chinese patients
Author(s) -
Fan Zichuan,
Ni Jinwen,
Yang Lin,
Hu Liyuan,
Ma Simin,
Mei Mei,
Sun Bijun,
Wang Huijun,
Zhou Wenhao
Publication year - 2015
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.162
Subject(s) - mutation , medicine , hyperinsulinemia , congenital hyperinsulinism , genetics , population , sanger sequencing , hyperinsulinism , gastroenterology , bioinformatics , biology , gene , insulin , insulin resistance , environmental health
Congenital hyperinsulinism ( CHI ) has been mostly associated with mutations in seven major genes. We retrospectively reviewed a cohort of 32 patients with CHI . Extensive mutational analysis ( ABCC 8 , KCNJ 11 , GCK , GLUD 1 , HADH , HNF 4A, and UCP 2 ) was performed on Ion torrent platform, which could analyze hundreds of genes simultaneously with ultrahigh‐multiplex PCR using up to 6144 primer pairs in a single primer pool and address time‐sensitive samples with single‐day assays, from samples to annotated variants, to identify the genetic etiology of this disease. Thirty‐seven sequence changes were identified, including in ABCC 8 / KCNJ 11 ( n = 25, 65.7%), GCK ( n = 2), HNF 4A ( n = 3), GLUD 1 ( n = 2), HADH ( n = 4), and UCP 2 ( n = 1); these mutations included 14 disease‐causing mutations, eight rare SNP s, 14 common SNP s, and one novel mutation. Mutations were identified in 21 of 32 patients (65.6%). Among the patients with an identified mutation, 14 had mutations in ABCC 8 , one of which was combined with a GLUD 1 mutation. Four patients had mutations in KCNJ 11 , 1 had a GCK mutation, 1 had a mutation in HADH , and two had a mutation in HNF 4A . Among the 32 patients, the age at the onset of hyperinsulinemia ranged from the neonatal period to 1 year of age; five patients underwent a pancreatectomy due to intractable hyperinsulinemia. This study describes novel and previously identified mutations in patients with CHI . The spectrum of mutations in CHI patients represents an important tool for the diagnosis and prognosis of CHI patients in the Chinese population as well as for the genetic counseling of CHI families.