Germline Mutation in NLRP2 (NALP2) in a Familial Imprinting Disorder (Beckwith-Wiedemann Syndrome)

Esther Meyer, Derek Lim, Shanaz Pasha, Louise Tee, Fatimah Rahman, Eamonn Maher

Research output: Contribution to journalArticlepeer-review

173 Citations (Scopus)
163 Downloads (Pure)


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 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 or maintaining genomic imprinting in humans.
Original languageEnglish
Pages (from-to)e1000423
JournalPLoS Genetics
Issue number3
Publication statusPublished - 1 Mar 2009


  • frameshift mutation
  • PANK2
  • PKAN
  • consanguineous
  • eye-of-the-tiger
  • pantothenate kinaseassociated neurodegeneration
  • neurodegeneration with brain iron accumulation


Dive into the research topics of 'Germline Mutation in NLRP2 (NALP2) in a Familial Imprinting Disorder (Beckwith-Wiedemann Syndrome)'. Together they form a unique fingerprint.

Cite this