title: Isodisomy of chromosome 6 in a newborn with methylmalonic acidemia and agenesis of pancreatic beta cells causing diabetes mellitus.
abstract: Isodisomy (ID) is a genetic anomaly defined as the inheritance of two copies of the same genetic material from one parent. ID in an offspring is a rare cause of recessive genetic diseases via inheritance of two copies of a mutated gene from one carrier parent. We studied a newborn female with a mut(o) of methylmalonic acidemia and complete absence of insulin-producing beta cells in otherwise normal-appearing pancreatic islets, causing insulin-dependent diabetes mellitus. The patient died 2 wk after birth. Serotyping of the HLA antigens, DNA typing of HLA-B and HLA class II loci, study of polymorphic DNA markers of chromosome 6, and cytogenetic analysis demonstrated paternal ID, involving at least a 25-centiMorgan portion of the chromosome pair that encompasses the MHC. ID probably caused methylmalonic acidemia by duplication of a mutated allele of the corresponding gene on the chromosome 6 inherited from the father. It is also very likely that ID was etiologically related to the agenesis of beta cells and consequent insulin-dependent diabetes mellitus in our patient. We thus speculate on the existence of a gene on chromosome 6 involved in beta cell differentiation.
authors.affiliation: Department of Genetics, University Hospital Erasme, Brussels, Belgium.
authors.forename: M J
authors.initials: MJ
authors.lastname: Abramowicz
authors.forename: M
authors.initials: M
authors.lastname: Andrien
authors.forename: E
authors.initials: E
authors.lastname: Dupont
authors.forename: H
authors.initials: H
authors.lastname: Dorchy
authors.forename: J
authors.initials: J
authors.lastname: Parma
authors.forename: L
authors.initials: L
authors.lastname: Duprez
authors.forename: F D
authors.initials: FD
authors.lastname: Ledley
authors.forename: W
authors.initials: W
authors.lastname: Courtens
authors.forename: E
authors.initials: E
authors.lastname: Vamos
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics; D002869:Chromosome Aberrations; D002896:Chromosomes, Human, Pair 6; D003922:Diabetes Mellitus, Type 1 / Q000151:congenital* / Q000209:etiology; D005260:Female; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D006801:Humans; D007231:Infant, Newborn; D007515:Islets of Langerhans / Q000002:abnormalities*; D008764:Methylmalonic Acid / Q000097:blood*; D008765:Methylmalonyl-CoA Mutase / Q000235:genetics; D010375:Pedigree
chemical_list: D008764:Methylmalonic Acid; D008765:Methylmalonyl-CoA Mutase