{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,7,9]],"date-time":"2023-07-09T15:10:54Z","timestamp":1688915454218},"reference-count":17,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1997,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Persistent hyperinsulinemic hypoglycemia of infancy (PHHI), a rare disorder due to defective negative feedback regulation of insulin secretion by low glucose levels, is often familial. Most cases are recessively inherited, and mutations of the sulfonylurea receptor gene (SUR) or the closely linked KIR6.2 gene have been found in several families. Both of these genes encode components of the potassium channels responsible for glucose-regulated insulin release. However, in some families recessive PHHI is not linked to the SUR-KIR6.2 locus, suggesting genetic heterogeneity. We report here a French Canadian kindred with hypoglycemia in five first cousins. All five patients had documented hypoglycemia, and all responded well to diazoxide. In two, inappropriately elevated insulin levels during hypoglycemia were documented. This familial clustering strongly suggests the existence of an autosomal dominant form of PHHI. By preliminary linkage analysis, we tested the possibility of a dominant negative SUR or KIR6.2 mutant. The insulin (INS) and glucokinase (GCK) genes were also tested as additional candidates. Microsatellite markers closely linked to each gene were used, and large negative Lod scores were obtained at the known recombination fractions between all three genes studied and the corresponding marker. We conclude that mutation of a gene other than SUR or KIR6.2 is responsible for the dominant PHHI in this family, and this gene cannot be INS or GCK. We propose that a genome-wide search for this gene is important for elucidating this rare disorder and, more importantly, for determining its potential impact on understanding noninsulin-dependent diabetes mellitus and on the effort to develop bioengineered \u03b2-cells for transplantation.<\/jats:p>","DOI":"10.1210\/jcem.82.4.3904","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:01:48Z","timestamp":1389200508000},"page":"1192-1194","source":"Crossref","is-referenced-by-count":1,"title":["An Autosomal Dominant Form of Familial Persistent Hyperinsulinemic Hypoglycemia of Infancy, Not Linked to the Sulfonylurea Receptor Locus*"],"prefix":"10.1210","volume":"82","author":[{"given":"Asterios","family":"Kukuvitis","sequence":"first","affiliation":[{"name":"Montreal Children\u2019s Hospital Research Institute, Department of Pediatrics, Division of Endocrinology, McGill University (A.K., L.A., C.P.), Montreal, Quebec, Canada;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheri","family":"Deal","sequence":"additional","affiliation":[{"name":"the Endocrinology Service, Sainte-Justine Hospital, University of Montreal (C.D.), Montreal, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Arbour","sequence":"additional","affiliation":[{"name":"Montreal Children\u2019s Hospital Research Institute, Department of Pediatrics, Division of Endocrinology, McGill University (A.K., L.A., C.P.), Montreal, Quebec, Canada;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Constantin","family":"Polychronakos","sequence":"additional","affiliation":[{"name":"Montreal Children\u2019s Hospital Research Institute, Department of Pediatrics, Division of Endocrinology, McGill University (A.K., L.A., C.P.), Montreal, Quebec, Canada;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071618160312600_R1","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/S0065-3101(22)00724-1","article-title":"Hyperinsulinism in infants and children: diagnosis and therapy.","volume":"32","author":"Stanley","year":"1976","journal-title":"Adv Pediatr"},{"key":"2020071618160312600_R2","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1097\/00008480-199008000-00024","article-title":"Recent advances in hyperinsulinism and the pathogenesis of diabetes mellitus.","volume":"2","author":"Bruining","year":"1990","journal-title":"Curr Opin Pediatr"},{"key":"2020071618160312600_R3","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/S0022-3476(05)80286-0","article-title":"Familial and sporadic hyperinsulinism: histopathologic findings and segregation analysis support a single recessive disorder.","volume":"119","author":"Thornton","year":"1991","journal-title":"J Pediatr"},{"key":"2020071618160312600_R4","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1136\/adc.51.7.528","article-title":"Idiopathic hypoglycaemia in sibs with morphological evidence of nesidioblastosis of the pancreas.","volume":"51","author":"Woo","year":"1976","journal-title":"Arch Dis Child"},{"key":"2020071618160312600_R5","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/S0022-3476(79)80080-3","article-title":"Familial nesidioblastosis: severe neonatal hypoglycemia in two families.","volume":"95","author":"Schwartz","year":"1979","journal-title":"J Pediatr"},{"key":"2020071618160312600_R6","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1126\/science.7716548","article-title":"Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of 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infancy.","volume":"2","author":"Kane","year":"1996","journal-title":"Nat Med"},{"key":"2020071618160312600_R10"},{"key":"2020071618160312600_R11","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1093\/hmg\/4.5.879","article-title":"Recombinant mapping of the familial hyperinsulinism gene to an 0.8 cM region on chromosome 11p15.1 and demonstration of a founder effect in Ashkenazi Jews.","volume":"4","author":"Glaser","year":"1995","journal-title":"Hum Mol Genet"},{"key":"2020071618160312600_R12","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/ng0793-305","article-title":"Susceptibility to insulin dependent diabetes mellitus maps to a 4.1 kb segment of DNA spanning the insulin gene and associated VNTR.","volume":"4","author":"Lucassen","year":"1993","journal-title":"Nat Genet"},{"key":"2020071618160312600_R13","first-page":"1070","article-title":"Human glucokinase gene: isolation, structural characterization, and identification of a microsatellite repeat polymorphism.","volume":"6","author":"Tanizawa","year":"1992","journal-title":"Mol Endocrinol"},{"key":"2020071618160312600_R14"},{"key":"2020071618160312600_R15"},{"key":"2020071618160312600_R16","doi-asserted-by":"crossref","first-page":"825","DOI":"10.2337\/diab.45.6.825","article-title":"Sequence variants in the sulfonylurea receptor (SUR) gene are associated with NIDDM in Caucasians.","volume":"45","author":"Inoue","year":"1996","journal-title":"Diabetes"},{"key":"2020071618160312600_R17"}],"container-title":["The Journal of Clinical Endocrinology &amp; 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