title: Atypical presentation of moyamoya disease in an infant with a de novo RNF213 variant.
abstract: Variants in RNF213 lead to susceptibility to moyamoya disease, a rare cerebral angiopathy characterized by bilateral stenosis of the internal carotid arteries and development of a compensatory collateral network. We describe a 3-month-old female with seizures, arterial narrowing involving the internal carotid and intracranial arteries and inferior abdominal aorta, and persistently elevated transaminases. Whole exome sequencing demonstrated a novel de novo variant in RNF213, securing a molecular diagnosis and directing appropriate intervention. This report underscores the role of whole exome sequencing in cases for which a complex and atypical presentation may mask diagnosis. Furthermore, the early and severe presentation in our patient, in conjunction with a novel de novo RNF213 variant, suggests that specific variants in RNF213 may lead to a Mendelian form of disease rather than simply conferring susceptibility to multifactorial disease.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Tamar
authors.initials: T
authors.lastname: Harel
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Posey
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Brett H
authors.initials: BH
authors.lastname: Graham
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Walkiewicz
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Seema R
authors.initials: SR
authors.lastname: Lalani
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: John W
authors.initials: JW
authors.lastname: Belmont
mesh_terms: D000251:Adenosine Triphosphatases; D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000473:pathology; D017124:Conserved Sequence; D019143:Evolution, Molecular; D059472:Exome / Q000235:genetics; D005190:Family; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009072:Moyamoya Disease / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics*
chemical_list: C557998:RNF213 protein, human; D044767:Ubiquitin-Protein Ligases; D000251:Adenosine Triphosphatases
keywords: moyamoya disease; whole exome sequencing