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Identification of a novel mutation in EXT2 in a fourthâgeneration Korean family with multiple osteochondromas and overview of mutation spectrum
- Source :
- Annals of Human Genetics. 83:160-170
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- Multiple osteochondromas (MOs) or hereditary multiple exostoses is a rare autosomal-dominant disease characterized by growths of MOs, which are benign cartilage-capped bone tumors that grow away from the growth plates. Almost 90% of MOs have a molecular explanation and 10% are unexplained. MOs are genetically heterogeneous with two causal genes on 8q24.11 (EXT1) and 11p12 (EXT2), with a higher frequency in EXT1. MO is a very rare genetic disorder, and the genotype-phenotype of MO with EXT2 mutation has not been well investigated in Korea. We present the clinical radiographic and molecular analysis of a four-generation Korean family with 11 MO-affected members (seven males and four females). The affected members from the third generation available for molecular analysis and their detailed medical histories showed moderate-to-severe phenotypes (clinical classes II-III), including bony deformities and limb misalignment with pain requiring surgical correction. The x-rays showed MOs in multiple sites. A novel EXT2 frameshift mutation (c.590delC, p.P197Qfs*73) was revealed by targeted exome sequencing in the affected members of this family. In this article, we not only expand the phenotypic-genotypic spectrum of MOs but also highlight the phenotypic heterogeneity in a family with the same mutation. In addition, we compiled the mutation spectrum of EXT2 from a literature review and identified that exon 2 of EXT2 is a mutation hot spot. Early medical attention with diagnosis of MO through careful examination of the clinical manifestations and genetic analysis can provide the opportunity to establish coordinated multispecialty management of the patient.
- Subjects :
- Adult
Male
Multiple osteochondroma
Hereditary multiple exostoses
Biology
N-Acetylglucosaminyltransferases
Genetic analysis
Frameshift mutation
03 medical and health sciences
Exon
Republic of Korea
Genetics
medicine
Humans
Child
Frameshift Mutation
Genetics (clinical)
Exome sequencing
030304 developmental biology
0303 health sciences
Genetic heterogeneity
030305 genetics & heredity
Genetic disorder
medicine.disease
Pedigree
Phenotype
Child, Preschool
Female
Exostoses, Multiple Hereditary
Subjects
Details
- ISSN :
- 14691809 and 00034800
- Volume :
- 83
- Database :
- OpenAIRE
- Journal :
- Annals of Human Genetics
- Accession number :
- edsair.doi.dedup.....c81cd67dd616e2fac581ceba89c30679