title: ARL6IP6, a susceptibility locus for ischemic stroke, is mutated in a patient with syndromic Cutis Marmorata Telangiectatica Congenita.
abstract: Cutis Marmorata Telangiectatica Congenita (CMTC) is a congenital localized or generalized vascular anomaly, usually sporadic in occurrence. It can be associated with other cutaneous or systemic manifestations. About 300 cases have been reported. The molecular etiology remains largely unknown. The main purpose of this study is to delineate the molecular basis for a syndromic CMTC phenotype in a consanguineous Saudi family. Clinical phenotyping including detailed neurological imaging, followed by autozygosity mapping and trio whole exome sequencing (WES) are also studied. We have identified a homozygous truncating mutation in ARL6IP6 as the likely cause of a syndromic form of CMTC associated with major dysmorphism, developmental delay, transient ischemic attacks and cerebral vascular malformations. This gene was previously implicated by genome wide association study (GWAS) as a susceptibility locus to ischemic stroke in young adults. We identify ARL6IP6 as a novel candidate gene for a syndromic form of CMTC. This suggests that ischemic stroke or transient ischemic attacks (TIA) may represent, at least in some cases, the mild end of a phenotypic spectrum that has at its severe end autosomal recessive CMTC. This finding contributes to a growing appreciation of the continuum of Mendelian and common complex diseases.
authors.affiliation: Developmental Genetics Unit, Department of Genetics, King Faisal Specialist Hospital and Research Center, MBC-03 PO BOX 3354, Riyadh, 11211, Saudi Arabia.
authors.forename: Iman S
authors.initials: IS
authors.lastname: Abumansour
authors.forename: Hadia
authors.initials: H
authors.lastname: Hijazi
authors.forename: Anas
authors.initials: A
authors.lastname: Alazmi
authors.forename: Fatma
authors.initials: F
authors.lastname: Alzahrani
authors.forename: Fahad A
authors.initials: FA
authors.lastname: Bashiri
authors.forename: Hamdy
authors.initials: H
authors.lastname: Hassan
authors.forename: Mohammed
authors.initials: M
authors.lastname: Alhaddab
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D000328:Adult; D002545:Brain Ischemia / Q000235:genetics*; D020785:Central Nervous System Vascular Malformations / Q000235:genetics*; D002675:Child, Preschool; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D054068:Livedo Reticularis; D008297:Male; D009154:Mutation; D017445:Skin Diseases, Vascular / Q000235:genetics*; D020521:Stroke / Q000235:genetics*; D013577:Syndrome; D013684:Telangiectasis / Q000151:congenital* / Q000235:genetics
chemical_list: D006360:Heat-Shock Proteins