Home Page

References

OMIM

Gene

GeneReviews

HGMD

HGNC

GENATLAS PHENOTYPE

last update : 20-06-2016

Symbol	PNDM2
Location	11p15.1
Name	permanent neonatal diabetes mellitus 2
Other name(s)	transient neonatal diabetes mellitus
Corresponding gene	ABCC8
Other symbol(s)	DEND, TNDM
Main clinical features	insulin-requiring hyperglycemia within the first 3 months of life, diabetes transient and resolving at a median age of 3 months, in about half of the neonates, whereas the rest have a permanent insulin-dependent form of diabetes
Genetic determination	not applicable
Prevalence	1 in 400,000 neonates
Related entries	including developmental delay, epilepsy, and neonatal diabetes (DEND syndrome)
Function/system disorder	endocrinology
	mental retardation
Type	disease

Mechanism(s)

Gene mutation	Chromosome rearrangement	Effect	Comments
missense		abnormal protein/gain of function	I1424V and H1023Y channels overactivating beta-cell K channels and increasing the magnesium -nucleotide-dependent stimulatory action of ABCC8 on the pore

Remark(s)

. two mutations on Transmembrane Helix 15 of ABCC8 Increase Affinity for ATP and ADP at Nucleotide Binding Domain 2 (PMID: 22451668))

Genotype/Phenotype correlations

PNDM2 resulting from compound heterozygous activating/inactivating mutations, the loss-of-function mutation leads to a decrease in functional protein, and the channels are essentially homomeric for the activating ABCC8 mutation mutation (R826W) in the first nucleotide-binding domain (NBD1), decreasing MgATP hydrolysis, reducing ATPase activity and leading to transient neonatal diabetes