Germline mutation in NLRP2 (NALP2) in a familial imprinting disorder (Beckwith-Wiedemann Syndrome).

Germline mutation in NLRP2 (NALP2) in a familial imprinting disorder (Beckwith-Wiedemann Syndrome).

Blog Article

Beckwith-Wiedemann syndrome (BWS) is a fetal overgrowth and human imprinting disorder resulting from the deregulation of a number of genes, including IGF2 and CDKN1C, in the imprinted gene cluster on chromosome 11p15.5.Most cases are sporadic and result from epimutations at either of the two 11p15.

5 imprinting centres (IC1 and IC2).However, rare familial cases may be associated with germline 11p15.5 deletions causing abnormal imprinting in cis.

We report a family with BWS and an IC2 epimutation in which affected duke waves and fades siblings had inherited different parental 11p15.5 alleles excluding an in cis mechanism.Using a positional-candidate gene approach, we found that the mother was homozygous for a frameshift mutation in exon 6 of NLRP2.

While germline mutations in NLRP7 have previously been associated with familial hydatidiform mole, this is the first description of NLRP2 mutation in human disease and the first report of a trans mechanism for disordered imprinting in BWS.These observations are consistent with the hypothesis that NLRP2 has a previously unrecognised role in establishing metabo 15-gauge finish nailer cordless or maintaining genomic imprinting in humans.