Novel mutations in theSDHD gene in pedigrees with familial carotid body paraganglioma and sensorineural hearing loss
| Autor: | Bora E. Baysal, Renee F. Badenhop, Peter E.M. Taschner, Reginald S. A. Lord, Peter R. Schofield, Sanjay M. Cherian |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Genetic Markers
Male Cancer Research Adolescent Genetic Linkage Hearing Loss Sensorineural Locus (genetics) Biology Carotid Body Tumor Loss of heterozygosity Tinnitus Exon Germline mutation Multienzyme Complexes Paraganglioma Mitochondrial Precursor Protein Import Complex Proteins Genetics medicine Humans Missense mutation Child Chromosomes Human Pair 11 Electron Transport Complex II Membrane Transport Proteins Proteins Intracellular Membranes Middle Aged medicine.disease Penetrance Molecular biology Mitochondria Pedigree Gene Expression Regulation Neoplastic Succinate Dehydrogenase Haplotypes Mutation Peptidyl Transferases Female SDHD Oxidoreductases |
| Zdroj: | Genes, Chromosomes and Cancer. 31:255-263 |
| ISSN: | 1098-2264 1045-2257 |
| DOI: | 10.1002/gcc.1142 |
| Popis: | Paraganglioma (PGL) is a rare disorder characterized by tumors of the head and neck region. Between 10% and 50% of cases of PGL are familial, and the disease is autosomal dominant and subject to age-dependent penetrance and imprinting. The paraganglioma gene (PGL1) has been mapped to 11q22.3–q23, and recently germline mutations in the SDHD gene have been identified. The SDHD region contains another gene, DPP2/TIMM8B, the homolog of which causes dystonia and deafness seen in Mohr-Tranebjaerg syndrome. Using four PGL pedigrees, two of which exhibit coinheritance of PGL and sensorineural hearing loss or tinnitus, analysis of 14 microsatellite markers provided support for linkage to the PGL1 locus. Sequence analysis identified novel mutations in exon 1 and exon 3 of the SDHD gene, including a novel two base pair deletion in exon 3 creating a premature stop codon at position 67; a novel three base pair deletion in exon 3 resulting in the loss of Tyr-93; a missense mutation in exon 3 resulting in the substitution of Leu-81 for Pro-81; and a novel G-to-C substitution in exon 1 resulting in the substitution of Met-1 for Ile-1. No base changes were detected in the DPP2/TIMM8B gene. There was no apparent loss of heterozygosity at the site of the SDHD mutations. However, RT-PCR analysis of tumor samples showed monoallelic expression of the mutant (paternal) allele as expected for imprinting. This has not previously been shown for this disorder. The inheritance and expression of the SDHD gene is consistent with the PGL1 gene being subject to genomic imprinting. © 2001 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text