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http://purl.uniprot.org/citations/23859901http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23859901http://www.w3.org/2000/01/rdf-schema#comment"

Background/aims

In a family with congenital hyperinsulinism (HI), first described in the 1950s by McQuarrie, we examined the genetic locus and clinical phenotype of a novel form of dominant HI.

Methods

We surveyed 25 affected individuals, 7 of whom participated in tests of insulin dysregulation (24-hour fasting, oral glucose and protein tolerance tests). To identify the disease locus and potential disease-associated mutations we performed linkage analysis, whole transcriptome sequencing, whole genome sequencing, gene capture, and next generation sequencing.

Results

Most affecteds were diagnosed with HI before age one and 40% presented with a seizure. All affecteds responded well to diazoxide. Affecteds failed to adequately suppress insulin secretion following oral glucose tolerance test or prolonged fasting; none had protein-sensitive hypoglycemia. Linkage analysis mapped the HI locus to Chr10q21-22, a region containing 48 genes. Three novel noncoding variants were found in hexokinase 1 (HK1) and one missense variant in the coding region of DNA2.

Conclusion

Dominant, diazoxide-responsive HI in this family maps to a novel locus on Chr10q21-22. HK1 is the more attractive disease gene candidate since a mutation interfering with the normal suppression of HK1 expression in beta-cells could readily explain the hypoglycemia phenotype of this pedigree."xsd:string
http://purl.uniprot.org/citations/23859901http://purl.org/dc/terms/identifier"doi:10.1159/000351943"xsd:string
http://purl.uniprot.org/citations/23859901http://purl.uniprot.org/core/author"Becker S."xsd:string
http://purl.uniprot.org/citations/23859901http://purl.uniprot.org/core/author"Ganguly A."xsd:string
http://purl.uniprot.org/citations/23859901http://purl.uniprot.org/core/author"Stanley C.A."xsd:string
http://purl.uniprot.org/citations/23859901http://purl.uniprot.org/core/author"Hakonarson H."xsd:string
http://purl.uniprot.org/citations/23859901http://purl.uniprot.org/core/author"Ganapathy K."xsd:string
http://purl.uniprot.org/citations/23859901http://purl.uniprot.org/core/author"Hughes N."xsd:string
http://purl.uniprot.org/citations/23859901http://purl.uniprot.org/core/author"Stokes D."xsd:string
http://purl.uniprot.org/citations/23859901http://purl.uniprot.org/core/author"Monos D."xsd:string
http://purl.uniprot.org/citations/23859901http://purl.uniprot.org/core/author"Mackiewicz K."xsd:string
http://purl.uniprot.org/citations/23859901http://purl.uniprot.org/core/author"Pinney S.E."xsd:string
http://purl.uniprot.org/citations/23859901http://purl.uniprot.org/core/author"Bradfield J."xsd:string
http://purl.uniprot.org/citations/23859901http://purl.uniprot.org/core/author"Sasson A."xsd:string
http://purl.uniprot.org/citations/23859901http://purl.uniprot.org/core/author"Boodhansingh K."xsd:string
http://purl.uniprot.org/citations/23859901http://purl.uniprot.org/core/author"Givler S."xsd:string
http://purl.uniprot.org/citations/23859901http://purl.uniprot.org/core/author"Macmullen C."xsd:string
http://purl.uniprot.org/citations/23859901http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23859901http://purl.uniprot.org/core/name"Horm Res Paediatr"xsd:string
http://purl.uniprot.org/citations/23859901http://purl.uniprot.org/core/pages"18-27"xsd:string
http://purl.uniprot.org/citations/23859901http://purl.uniprot.org/core/title"Dominant form of congenital hyperinsulinism maps to HK1 region on 10q."xsd:string
http://purl.uniprot.org/citations/23859901http://purl.uniprot.org/core/volume"80"xsd:string
http://purl.uniprot.org/citations/23859901http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/23859901
http://purl.uniprot.org/citations/23859901http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/23859901
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