Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis
B Isidor, P Lindenbaum, O Pichon, S Bézieau, C Dina… - Nature …, 2011 - nature.com
Nature genetics, 2011•nature.com
Hajdu-Cheney syndrome is a rare autosomal dominant skeletal disorder with facial
anomalies, osteoporosis and acro-osteolysis. We sequenced the exomes of six unrelated
individuals with this syndrome and identified heterozygous nonsense and frameshift
mutations in NOTCH2 in five of them. All mutations cluster to the last coding exon of the
gene, suggesting that the mutant mRNA products escape nonsense-mediated decay and
that the resulting truncated NOTCH2 proteins act in a gain-of-function manner.
anomalies, osteoporosis and acro-osteolysis. We sequenced the exomes of six unrelated
individuals with this syndrome and identified heterozygous nonsense and frameshift
mutations in NOTCH2 in five of them. All mutations cluster to the last coding exon of the
gene, suggesting that the mutant mRNA products escape nonsense-mediated decay and
that the resulting truncated NOTCH2 proteins act in a gain-of-function manner.
Abstract
Hajdu-Cheney syndrome is a rare autosomal dominant skeletal disorder with facial anomalies, osteoporosis and acro-osteolysis. We sequenced the exomes of six unrelated individuals with this syndrome and identified heterozygous nonsense and frameshift mutations in NOTCH2 in five of them. All mutations cluster to the last coding exon of the gene, suggesting that the mutant mRNA products escape nonsense-mediated decay and that the resulting truncated NOTCH2 proteins act in a gain-of-function manner.
nature.com
