title: Uncovering the molecular pathogenesis of congenital hyperinsulinism by panel gene sequencing in 32 Chinese patients.
abstract: 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 (ABCC8,KCNJ11,GCK,GLUD1,HADH,HNF4A, and UCP2) 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 ABCC8/KCNJ11 (n = 25, 65.7%), GCK (n = 2), HNF4A (n = 3), GLUD1 (n = 2), HADH (n = 4), and UCP2 (n = 1); these mutations included 14 disease-causing mutations, eight rare SNPs, 14 common SNPs, 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 ABCC8, one of which was combined with a GLUD1 mutation. Four patients had mutations in KCNJ11, 1 had a GCK mutation, 1 had a mutation in HADH, and two had a mutation in HNF4A. 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.
authors.affiliation: Department of NeonatologyChildren's Hospital of Fudan UniversityShanghaiChina; Key Laboratory of Birth DefectChildren's Hospital of Fudan UniversityShanghaiChina.
authors.forename: Zi-Chuan
authors.initials: ZC
authors.lastname: Fan
authors.affiliation: Department of Neonatology Children's Hospital of Fudan University Shanghai China.
authors.forename: Jin-Wen
authors.initials: JW
authors.lastname: Ni
authors.affiliation: Key Laboratory of Birth DefectChildren's Hospital of Fudan UniversityShanghaiChina; Key Laboratory of Neonatal DiseasesMinistry of HealthChildren's HospitalFudan UniversityShanghaiChina.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Neonatology Children's Hospital of Fudan University Shanghai China.
authors.forename: Li-Yuan
authors.initials: LY
authors.lastname: Hu
authors.affiliation: Department of Neonatology Children's Hospital of Fudan University Shanghai China.
authors.forename: Si-Min
authors.initials: SM
authors.lastname: Ma
authors.affiliation: Department of Neonatology Children's Hospital of Fudan University Shanghai China.
authors.forename: Mei
authors.initials: M
authors.lastname: Mei
authors.affiliation: Department of NeonatologyChildren's Hospital of Fudan UniversityShanghaiChina; Key Laboratory of Birth DefectChildren's Hospital of Fudan UniversityShanghaiChina.
authors.forename: Bi-Jun
authors.initials: BJ
authors.lastname: Sun
authors.affiliation: Key Laboratory of Birth DefectChildren's Hospital of Fudan UniversityShanghaiChina; Key Laboratory of Neonatal DiseasesMinistry of HealthChildren's HospitalFudan UniversityShanghaiChina.
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Department of NeonatologyChildren's Hospital of Fudan UniversityShanghaiChina; Key Laboratory of Birth DefectChildren's Hospital of Fudan UniversityShanghaiChina; Key Laboratory of Neonatal DiseasesMinistry of HealthChildren's HospitalFudan UniversityShanghaiChina.
authors.forename: Wen-Hao
authors.initials: WH
authors.lastname: Zhou
keywords: Clinical diagnosis; congenital hyperinsulinism; mutation spectra