Heterozygous nonsense mutation SATB2 associated with cleft palate, osteoporosis, and cognitive defects.
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.
Leoyklang
Petcharat
P
Department of Pediatrics, Chulalongkorn University, Bangkok, Thailand.
Suphapeetiporn
Kanya
K
Siriwan
Pichit
P
Desudchit
Tayard
T
Chaowanapanja
Pattraporn
P
Gahl
William A
WA
Shotelersuk
Vorasuk
V
D000328:Adult; D001483:Base Sequence; D002972:Cleft Palate / Q000235:genetics*; D018389:Codon, Nonsense; D003072:Cognition Disorders / Q000235:genetics*; D017931:DNA Primers; D005091:Exons; D006579:Heterozygote; D006801:Humans; D008297:Male; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics*; D010024:Osteoporosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*
D018389:Codon, Nonsense; D017931:DNA Primers; D036961:Matrix Attachment Region Binding Proteins; C521297:SATB2 protein, human; D014157:Transcription Factors