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

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(...

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Bibliographic Details
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
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Summary: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.
ISSN:0021-9738
DOI:10.1172/JCI117339