Isodisomy of chromosome 6 in a newborn with methylmalonic acidemia and agenesis of pancreatic beta cells causing diabetes mellitus

• Published in: The Journal of clinical investigation 1994-07, Vol.94 (1), p.418-421
• Main Authors: Abramowicz, M J, Andrien, M, Dupont, E, Dorchy, H, Parma, J, Duprez, L, Ledley, F D, Courtens, W, Vamos, E
• Format: Article
• Language: English
• Subjects: Amino Acid Metabolism, Inborn Errors - genetics; chromosome 6; Chromosome Aberrations; Chromosomes, Human, Pair 6; diabetes mellitus; Diabetes Mellitus, Type 1 - congenital; Diabetes Mellitus, Type 1 - etiology; DNA; Female; Genes, MHC Class I; Genes, MHC Class II; Humans; Infant, Newborn; Islets of Langerhans - abnormalities; isodisomy; man; Methylmalonic Acid - blood; methylmalonic acidemia; Methylmalonyl-CoA Mutase - genetics; Pedigree
• ISSN: 0021-9738
• DOI: 10.1172/JCI117339

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.