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Heterozygous nonsense mutation SATB2 associated with cleft palate, osteoporosis, and cognitive defects
Author(s) -
Leoyklang Petcharat,
Suphapeetiporn Kanya,
Siriwan Pichit,
Desudchit Tayard,
Chaowanapanja Pattraporn,
Gahl William A,
Shotelersuk Vorasuk
Publication year - 2007
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.20515
Subject(s) - craniofacial , biology , genetics , nonsense mutation , exon , mutation , germline mosaicism , nonsense , gene , missense mutation
Studies of human chromosomal aberrations and knockout (KO) mice have suggested SATB2 as a candidate gene for a human malformation syndrome of craniofacial patterning and brain development. Of 59 unrelated patients with craniofacial dysmorphism, with or without mental retardation, one 36‐year‐old man had a nonsynonymous mutation in SATB2 . The affected individual exhibited craniofacial dysmorphisms including cleft palate, generalized osteoporosis, profound mental retardation, epilepsy and a jovial personality. He carries a de novo germline nonsense mutation (c.715C>T, p.R239X) in the exon 6 of SATB2 . Expression studies showed that the mutant RNA was stable, expected to produce a truncated protein predicted to retain its dimerization domain and exert a dominant negative effect. This new syndrome is the first determined to result from mutation of a gene within the family that encodes nuclear matrix‐attachment region (MAR) proteins. Hum Mutat 28(7), 732–738, 2007. Published 2007 Wiley‐Liss, Inc.