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Clin Genet. 2015 Oct;88(4):386-90. doi: 10.1111/cge.12511. Epub 2014 Dec 5.

The RBMX gene as a candidate for the Shashi X-linked intellectual disability syndrome.

Author information

1
Department of Pediatrics, Division of Medical Genetics, Duke University Medical Sciences, Durham, NC, USA.
2
Center for Human Genome Variation, Duke University School of Medicine, Durham, NC, USA.
3
Department of Pediatrics, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
4
Greenwood Genetic Center, Greenwood, SC, USA.
5
Department of Biostatistics, Duke University Health Sciences, Durham, NC, USA.
6
Division of Brain Sciences, Imperial College, London, UK.

Abstract

A novel X-linked intellectual disability (XLID) syndrome with moderate intellectual disability and distinguishing craniofacial dysmorphisms had been previously mapped to the Xq26-q27 interval. On whole exome sequencing in the large family originally reported with this disorder, we identified a 23 bp frameshift deletion in the RNA binding motif protein X-linked (RBMX) gene at Xq26 in the affected males (n = 7), one carrier female, absent in unaffected males (n = 2) and in control databases (7800 exomes). The RBMX gene has not been previously causal of human disease. We examined the genic intolerance scores for the coding regions and the non-coding regions of RBMX; the findings were indicative of RBMX being relatively intolerant to loss of function variants, a distinctive pattern seen in a subset of XLID genes. Prior expression and animal modeling studies indicate that loss of function of RBMX results in abnormal brain development. Our finding putatively adds a novel gene to the loci associated with XLID and may enable the identification of other individuals affected with this distinctive syndrome.

KEYWORDS:

Shashi syndrome; X-linked intellectual disability; X-linked mental retardation; whole exome sequencing

PMID:
25256757
DOI:
10.1111/cge.12511
[Indexed for MEDLINE]
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