title: The RBMX gene as a candidate for the Shashi X-linked intellectual disability syndrome.
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.
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, Duke University Medical Sciences, Durham, NC, USA.
authors.forename: V
authors.initials: V
authors.lastname: Shashi
authors.affiliation: Center for Human Genome Variation, Duke University School of Medicine, Durham, NC, USA.
authors.forename: P
authors.initials: P
authors.lastname: Xie
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, Duke University Medical Sciences, Durham, NC, USA.
authors.forename: K
authors.initials: K
authors.lastname: Schoch
authors.affiliation: Center for Human Genome Variation, Duke University School of Medicine, Durham, NC, USA.
authors.forename: D B
authors.initials: DB
authors.lastname: Goldstein
authors.affiliation: Department of Pediatrics, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
authors.forename: T D
authors.initials: TD
authors.lastname: Howard
authors.affiliation: Department of Pediatrics, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
authors.forename: M N
authors.initials: MN
authors.lastname: Berry
authors.affiliation: Greenwood Genetic Center, Greenwood, SC, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Schwartz
authors.affiliation: Center for Human Genome Variation, Duke University School of Medicine, Durham, NC, USA.
authors.forename: K
authors.initials: K
authors.lastname: Cronin
authors.affiliation: Center for Human Genome Variation, Duke University School of Medicine, Durham, NC, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sliwa
authors.affiliation: Department of Biostatistics, Duke University Health Sciences, Durham, NC, USA.
authors.forename: A
authors.initials: A
authors.lastname: Allen
authors.affiliation: Division of Brain Sciences, Imperial College, London, UK.
authors.forename: A C
authors.initials: AC
authors.lastname: Need
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D056726:Genetic Association Studies; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics*; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; C510272:RBMX protein, human
keywords: Shashi syndrome; X-linked intellectual disability; X-linked mental retardation; whole exome sequencing