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Mutations in NOTCH2 in families with Hajdu‐Cheney syndrome
Author(s) -
Majewski Jacek,
Schwartzentruber Jeremy A.,
Caqueret Aurore,
Patry Lysanne,
Marcadier Janet,
Fryns JeanPierre,
Boycott Kym M.,
SteMarie LouisGeorges,
McKiernan Fergus E.,
Marik Ivo,
Van Esch Hilde,
Michaud Jacques L.,
Samuels Mark E.
Publication year - 2011
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.21546
Subject(s) - biology , genetics , notch signaling pathway , phenotype , allele , gene , hum , mutation , bioinformatics , art , performance art , art history
Hajdu‐Cheney syndrome (HCS) is a rare genetic disorder whose hallmark is acro‐osteolysis, shortening of terminal phalanges, and generalized osteoporosis. We assembled a cohort of seven families with the condition and performed whole exome resequencing on a selected set of affected patients. One protein‐coding gene, NOTCH2 , carried heterozygous truncating variants in all patients and their affected family members. Our results replicate recently published studies of HCS and further support this as the causal gene for the disorder. In total, we identified five novel and one previously reported mutation, all clustered near the carboxyl terminus of the gene, suggesting an allele specific genotype‐phenotype effect since other mutations in NOTCH2 have been reported to cause a form of Alagille syndrome. Notch‐mediated signaling is known to play a role in bone metabolism. Our results support a potential therapeutic role for Notch pathways in treatment of osteoporosis. Hum Mutat 32:1114–1117, 2011. ©2011 Wiley‐Liss, Inc.