Dataset Information

Identification of two novel mutations in the SLC45A2 gene in a Hungarian pedigree affected by unusual OCA type 4.

ABSTRACT: 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.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.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.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.

SUBMITTER: Toth L

PROVIDER: S-EPMC5353789 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Identification of two novel mutations in the SLC45A2 gene in a Hungarian pedigree affected by unusual OCA type 4.

Tóth Lola L Fábos Beáta B Farkas Katalin K Sulák Adrienn A Tripolszki Kornélia K Széll Márta M Nagy Nikoletta N

BMC medical genetics 20170315 1

<h4>Background</h4>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.<h4>Method ...[more]

PMID: 28298193

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Project description:DNA typing is an important tool in missing-person identification, especially in mass-fatality disasters. Identification methods comparing a DNA profile from unidentified human remains with that of a direct (from the person) or indirect (for example, from a biological relative) reference sample and ranking the pairwise likelihood ratios (LR) is straightforward and well defined. However, for indirect comparison cases in which several members from a family can serve as reference samples, the full power of kinship analysis is not entirely exploited. Because biologically related family members are not genetically independent, more information and thus greater power can be attained by simultaneous use of all pedigree members in most cases, although distant relationships may reduce the power. In this study, an improvement was made on the method for missing-person identification for autosomal and lineage-based markers, by considering jointly the DNA profile data of all available family reference samples. The missing person is evaluated by a pedigree LR of the probability of DNA evidence under alternative hypotheses (for example, the missing person is unrelated or if they belong to this pedigree with a specified biological relationship) and can be ranked for all pedigrees within a database. Pedigree LRs are adjusted for population substructure according to the recommendations of the second National Research Council (NRCII) Report. A realistic mutation model was also incorporated to accommodate the possibility of false exclusion. The results show that the effect of mutation on the pedigree LR is moderate, but LRs can be significantly decreased by the effect of population substructure. Finally, Y chromosome and mitochondrial DNA were integrated into the analysis to increase the power of identification. A program titled MPKin was developed, combining the aforementioned features to facilitate genetic analysis for identifying missing persons. The computational complexity of the algorithms is explained, and several ways to reduce the complexity are introduced.

Dataset Information

Identification of two novel mutations in the SLC45A2 gene in a Hungarian pedigree affected by unusual OCA type 4.

Publications

Identification of two novel mutations in the SLC45A2 gene in a Hungarian pedigree affected by unusual OCA type 4.

Similar Datasets

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