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

Lola Tóth, Beáta Fábos, Katalin Farkas, Adrienn Sulák, Kornélia Tripolszki, M. Széll, N. Nagy

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number27
JournalBMC Medical Genetics
Volume18
Issue number1
DOIs
Publication statusPublished - Mar 15 2017

Fingerprint

Pedigree
Mutation
Monophenol Monooxygenase
Genes
Computer Simulation
Oculocutaneous Albinism
Genetic Databases
Membrane Transport Proteins
Melanins
Pigmentation
Missense Mutation
Type IV Oculocutaneous Albinism
Siblings
Copper
Membrane Proteins
Phenotype
DNA

Keywords

  • Compound heterozygous state
  • Novel mutations
  • Oculocutaneous albinism type 4
  • SLC45A2 gene
  • Unusual phenotype

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Identification of two novel mutations in the SLC45A2 gene in a Hungarian pedigree affected by unusual OCA type 4. / Tóth, Lola; Fábos, Beáta; Farkas, Katalin; Sulák, Adrienn; Tripolszki, Kornélia; Széll, M.; Nagy, N.

In: BMC Medical Genetics, Vol. 18, No. 1, 27, 15.03.2017.

Research output: Contribution to journalArticle

Tóth, Lola ; Fábos, Beáta ; Farkas, Katalin ; Sulák, Adrienn ; Tripolszki, Kornélia ; Széll, M. ; Nagy, N. / Identification of two novel mutations in the SLC45A2 gene in a Hungarian pedigree affected by unusual OCA type 4. In: BMC Medical Genetics. 2017 ; Vol. 18, No. 1.
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AB - 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.

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