Mj. Abramowicz et al., ISODISOMY OF CHROMOSOME-6 IN A NEWBORN WITH METHYLMALONIC ACIDEMIA AND AGENESIS OF PANCREATIC BETA-CELLS CAUSING DIABETES-MELLITUS, The Journal of clinical investigation, 94(1), 1994, pp. 418-421
Isodisomy (ID) is a genetic anomaly defined as the inheritance of two
copies of the same genetic material from one parent. ID in an off spri
ng is a rare cause of recessive genetic diseases via inheritance of tw
o copies of a mutated gene from one carrier parent. We studied a newbo
rn female with a mut(o) form of methylmalonic acidemia and complete ab
sence of insulin-producing beta cells in otherwise normal-appearing pa
ncreatic islets, causing insulin-dependent diabetes mellitus. The pati
ent died 2 wk after birth. Serotyping of the HLA I antigens, DNA typin
g of HLA-B and HLA class II loci, study of polymorphic DNA markers of
chromosome 6, and cytogenetic analysis demonstrated paternal ID, invol
ving at least a 25-centiMorgan portion of the chromosome pair that enc
ompasses the MHC. LD probably caused methylmalonic acidemia by duplica
tion of a mutated allele of the corresponding gene on the chromosome 6
inherited from the father. It is also very likely that ID was etiolog
ically related to the agenesis of beta cells and consequent insulin-de
pendent diabetes mellitus in our patient. We thus speculate on the exi
stence of a gene on chromosome 6 involved in beta cell differentiation
.