Germline CBL mutation associated with a noonan-like syndrome with primary lymphedema and teratoma associated with acquired uniparental isodisomy of chromosome 11q23.
Germline mutations in the gene CBL (Casitas B-lineage lymphoma), involved in the RAS-MAPK signaling pathway, have been found as a rare cause of the neuro-cardio-facial-cutaneous syndromes. Somatically acquired homozygous CBL mutations were initially identified in association with myeloproliferative disorders, particularly juvenile myelomonocytic leukemia (JMML). We describe a girl with a Noonan-like phenotype of bilateral ptosis, lymphedema of the lower limbs and moderate intellectual disability, due to a de novo heterozygous mutation in CBL. She developed an ovarian mixed germ cell/teratoma with later occurrence of mature liver, omental, and ovarian teratomas. Copy neutral loss of heterozygosity for the CBL mutation due to acquired segmental uniparental disomy of 11q23 was observed in three teratomas, suggesting a specific association of CBL mutations in germ cell tumor predisposition.
SW Thames Regional Genetics Service, St George's Healthcare NHS Trust, London, UK.
Helen L
HL
Hanson
Meredith J
MJ
Wilson
John P
JP
Short
Barry A
BA
Chioza
Andrew H
AH
Crosby
Ruth M
RM
Nash
Karen J
KJ
Marks
Sahar
S
Mansour
D000293:Adolescent; D002880:Chromosomes, Human, Pair 11; D005260:Female; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008209:Lymphedema / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics*; D013724:Teratoma / Q000235:genetics*; D024182:Uniparental Disomy / Q000235:genetics*
D050721:Proto-Oncogene Proteins c-cbl; C067419:CBL protein, human
CBL; Growing Teratoma Syndrome (GTS); germinoma; lymphedema; noonan; teratoma