Premium
Identification of a novel mutation of SH3BP2 in cherubism and demonstration that SH3BP2 mutations lead to increased NFAT activation
Author(s) -
Lietman Steven A.,
Kalinchinko Natasha,
Deng Xichao,
Kohanski Ronald,
Levine Michael A.
Publication year - 2006
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9433
Subject(s) - cherubism , nfat , biology , missense mutation , exon , mutation , genetics , phenotype , microbiology and biotechnology , point mutation , gene , transcription factor , giant cell
Abstract We describe a novel missense mutation (Aspartic acid to Asparagine, p.D419N (g.1371G>A, c.1255G>A) within exon 9 of SH3BP2 in a patient with cherubism, an autosomal dominant syndrome characterized by excessive osteoclastic bone resorption of the jaw. Two siblings and the father were carriers but lacked phenotypic features. Transient expression of p.D419N (c.1255G>A), as well as three previously described exon 9 mutations from cherubism patients (p.R415Q (c.1244G>A), p.D420E (c.1259G>A), and p.P418R (c.1253C>G)) increased activity of NFAT (nuclear factor of activated T‐cells), an osteoclastogenic mediator, indicating that cherubism results from gain of function mutations in SH3BP2 . Published 2006 Wiley‐Liss, Inc.