title: Germline mutation of CBL is associated with moyamoya disease in a child with juvenile myelomonocytic leukemia and Noonan syndrome-like disorder.
abstract: Germline mutations in CBL have been identified in patients with Noonan syndrome-like phenotypes, while juvenile myelomonocytic leukemia (JMML) harbors duplication of a germline CBL, resulting in acquired isodisomy. The association between moyamoya disease and Noonan syndrome carrying a PTPN11 mutation has recently been reported. We present a patient with JMML who developed moyamoya disease and neovascular glaucoma. Our patient exhibited a Noonan syndrome-like phenotype. Genetic analysis revealed acquired isodisomy and a germline heterozygous mutation in CBL. This is a rare case of CBL mutation associated with moyamoya disease. Prolonged RAS pathway signaling may cause disruption of cerebrovascular development.
authors.affiliation: Center of Bone Marrow Transplantation, Hospital of University of the Ryukyus, Nishihara, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hyakuna
authors.forename: Hideki
authors.initials: H
authors.lastname: Muramatsu
authors.forename: Takeshi
authors.initials: T
authors.lastname: Higa
authors.forename: Yasutsugu
authors.initials: Y
authors.lastname: Chinen
authors.forename: Xinan
authors.initials: X
authors.lastname: Wang
authors.forename: Seiji
authors.initials: S
authors.lastname: Kojima
mesh_terms: D002648:Child; D005260:Female; D006801:Humans; D054429:Leukemia, Myelomonocytic, Juvenile / Q000235:genetics* / Q000378:metabolism; D009072:Moyamoya Disease / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009634:Noonan Syndrome / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000378:metabolism; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D050721:Proto-Oncogene Proteins c-cbl; D015689:Oncogene Protein p21(ras); C067419:CBL protein, human
keywords: CBL; Noonan syndrome-like disorder; juvenile myelomonocytic leukemia; moyamoya disease