Identification of Two Novel Mutations in the SLC45A2 Gene in a Hungarian Pedigree Affected by Unusual OCA Type 4
| Autor: | L. Tóth, Adrienn Sulák, Kornélia Tripolszki, B. Fábos, Márta Széll, Katalin Farkas, Nikoletta Nagy |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Adult SLC45A2 Tyrosinase Mutation Missense Unusual phenotype Compound heterozygous state Compound heterozygosity medicine.disease_cause White People 03 medical and health sciences 0302 clinical medicine Oculocutaneous albinism type 4 Antigens Neoplasm Genetics medicine Humans Missense mutation Genetics(clinical) Gene Genetics (clinical) Hungary Mutation biology Membrane Transport Proteins Sequence Analysis DNA SLC45A2 gene medicine.disease Molecular biology Oculocutaneous albinism Novel mutations Pedigree 030104 developmental biology Phenotype Albinism Oculocutaneous Codon Nonsense 030220 oncology & carcinogenesis biology.protein Female Research Article |
| Zdroj: | BMC Medical Genetics |
| ISSN: | 2161-1041 |
| DOI: | 10.4172/2161-1041.s7-006 |
| Popis: | Background Oculocutaneous albinism (OCA) is a clinically and genetically heterogenic group of pigmentation abnormalities. OCA type IV (OCA4, OMIM 606574) develops due to homozygous or compound heterozygous mutations in the solute carrier family 45, member 2 (SLC45A2) gene. This gene encodes a membrane-associated transport protein, which regulates tyrosinase activity and, thus, melanin content by changing melanosomal pH and disrupting the incorporation of copper into tyrosinase. Methods Here we report two Hungarian siblings affected by an unusual OCA4 phenotype. After genomic DNA was isolated from peripheral blood of the patients, the coding regions of the SLC45A2 gene were sequenced. In silico tools were applied to identify the functional impact of the newly detected mutations. Results Direct sequencing of the SLC45A2 gene revealed two novel, heterozygous mutations, one missense (c.1226G > A, p.Gly409Asp) and one nonsense (c.1459C > T, p.Gln437*), which were present in both patients, suggesting the mutations were compound heterozygous. In silico tools suggest that these variations are disease causing mutations. Conclusions The newly identified mutations may affect the transmembrane domains of the protein, and could impair transport function, resulting in decreases in both melanosomal pH and tyrosinase activity. Our study provides expands on the mutation spectrum of the SLC45A2 gene and the genetic background of OCA4. |
| Databáze: | OpenAIRE |
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