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Author Kosaki, Rika ♦ Takenouchi, Toshiki ♦ Takeda, Noriko ♦ Kagami, Masayo ♦ Nakabayashi, Kazuhiko ♦ Hata, Kenichiro ♦ Kosaki, Kenjiro
Source World Health Organization (WHO)-Global Index Medicus
Content type Text
Publisher Wiley-Blackwell
File Format HTM / HTML
Language English
Difficulty Level Medium
Subject Domain (in DDC) Natural sciences & mathematics ♦ Chemistry & allied sciences ♦ Life sciences; biology ♦ Physiology & related subjects ♦ Biochemistry ♦ Genetics and evolution ♦ Natural history of organisms ♦ Technology ♦ Medicine & health ♦ Human physiology ♦ Pharmacology and therapeutics ♦ Diseases
Subject Domain (in MeSH) Eukaryota ♦ Organisms ♦ Neoplasms ♦ Musculoskeletal Diseases ♦ Nervous System Diseases ♦ Cardiovascular Diseases ♦ Congenital, Hereditary, and Neonatal Diseases and Abnormalities ♦ Diseases ♦ Amino Acids, Peptides, and Proteins ♦ Chemicals and Drugs ♦ Genetic Phenomena ♦ Biological Sciences ♦ Persons ♦ Persons
Subject Keyword Discipline Human ♦ Discipline Genetics ♦ Arrhythmias, Cardiac ♦ Genetics ♦ Genetic Diseases, X-linked ♦ Germ-line Mutation ♦ Gigantism ♦ Glypicans ♦ Heart Defects, Congenital ♦ Hepatoblastoma ♦ Intellectual Disability ♦ Liver Neoplasms ♦ Mutation ♦ Beta Catenin ♦ Humans ♦ Infant ♦ Male ♦ Case Reports ♦ Journal Article ♦ Research Support, Non-u.s. Gov't
Abstract Simpson-Golabi-Behmel syndrome is a rare overgrowth syndrome caused by the GPC3 mutation at Xq26 and is clinically characterized by multiple congenital abnormalities, intellectual disability, pre/postnatal overgrowth, distinctive craniofacial features, macrocephaly, and organomegaly. Although this syndrome is known to be associated with a risk for embryonal tumors, similar to other overgrowth syndromes, the pathogenetic basis of this mode of tumorigenesis remains largely unknown. Here, we report a boy with Simpson-Golabi-Behmel syndrome who had a germline loss-of function mutation in GPC3. At 9 months of age, he developed hepatoblastoma. A comparison of exome analysis results for the germline genome and for the tumor genome revealed a somatic mutation, p.Ile35Ser, within the degradation targeting box of ß-catenin. The same somatic mutation in CTNNB1 has been repeatedly reported in hepatoblastoma and other cancers. This finding suggested that the CTNNB1 mutation in the tumor tissue represents a driver mutation and that both the GPC3 and the CTNNB1 mutations contributed to tumorigenesis in a clearly defined sequential manner in the propositus. The current observation of a somatic CTNNB1 mutation in a hepatoblastoma from a patient with a germline GPC3 mutation supports the notion that the mutation in GPC3 may influence one of the initial steps in tumorigenesis and the progression to hepatoblastoma.
Description Country affiliation: Japan
Author Affiliation: Kosaki R ( Division of Medical Genetics, National Center for Child Health and Development, Tokyo, Japan.)
ISSN 15524825
Educational Role Student ♦ Teacher
Age Range above 22 year
Educational Use Reading ♦ Research ♦ Self Learning
Interactivity Type Expositive
Education Level UG and PG
Learning Resource Type Article ♦ Case study
Publisher Date 2014-04-01
Publisher Place United States
e-ISSN 15524833
Journal American Journal of Medical Genetics Part A
Volume Number 164A
Issue Number 4


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Source: WHO-Global Index Medicus