title: 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.
authors.affiliation: Department of Medical Genetics, University of Szeged, 6 Somogyi Bela Street, 6720, Szeged, Hungary.
authors.forename: Lola
authors.initials: L
authors.lastname: Tóth
authors.affiliation: Mór Kaposi Teaching Hospital of the Somogy County, Kaposvár, Hungary.
authors.forename: Beáta
authors.initials: B
authors.lastname: Fábos
authors.affiliation: MTA-SZTE Dermatological Research Group, University of Szeged, Szeged, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Farkas
authors.affiliation: Department of Medical Genetics, University of Szeged, 6 Somogyi Bela Street, 6720, Szeged, Hungary.
authors.forename: Adrienn
authors.initials: A
authors.lastname: Sulák
authors.affiliation: Department of Medical Genetics, University of Szeged, 6 Somogyi Bela Street, 6720, Szeged, Hungary.
authors.forename: Kornélia
authors.initials: K
authors.lastname: Tripolszki
authors.affiliation: Department of Medical Genetics, University of Szeged, 6 Somogyi Bela Street, 6720, Szeged, Hungary.|MTA-SZTE Dermatological Research Group, University of Szeged, Szeged, Hungary.
authors.forename: Márta
authors.initials: M
authors.lastname: Széll
authors.affiliation: Department of Medical Genetics, University of Szeged, 6 Somogyi Bela Street, 6720, Szeged, Hungary. nagy.nikoletta@med.u-szeged.hu.|MTA-SZTE Dermatological Research Group, University of Szeged, Szeged, Hungary. nagy.nikoletta@med.u-szeged.hu.|Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary. nagy.nikoletta@med.u-szeged.hu.
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Nagy
mesh_terms: D000328:Adult; D016115:Albinism, Oculocutaneous / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000235:genetics*; D018389:Codon, Nonsense; D005260:Female; D006801:Humans; D006814:Hungary; D026901:Membrane Transport Proteins / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA / Q000379:methods; D044465:White People / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D018389:Codon, Nonsense; D026901:Membrane Transport Proteins; C510061:SLC45A2 protein, human
keywords: Compound heterozygous state; Novel mutations; Oculocutaneous albinism type 4; SLC45A2 gene; Unusual phenotype