Heterozygous nonsense mutation SATB2 associated with cleft palate, osteoporosis, and cognitive defects
✍ Scribed by Petcharat Leoyklang; Kanya Suphapeetiporn; Pichit Siriwan; Tayard Desudchit; Pattraporn Chaowanapanja; William A Gahl; Vorasuk Shotelersuk
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 358 KB
- Volume
- 28
- Category
- Article
- ISSN
- 1059-7794
No coin nor oath required. For personal study only.
✦ Synopsis
Communicated by Iain McIntosh
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.715C4T, 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.