TY - JOUR
T1 - Birth prevalence and mutation spectrum in danish patients with autosomal recessive albinism
AU - Grønskov, Karen
AU - Ek, Jakob
AU - Sand, Annie
AU - Scheller, Rudolf
AU - Bygum, Anette
AU - Brixen, Kim
AU - Brøndum-Nielsen, Karen
AU - Rosenberg, Thomas
N1 - Keywords: Adolescent; Adult; Aged; Albinism, Oculocutaneous; Alleles; Antigens, Neoplasm; Antiporters; Child; Child, Preschool; Chromatography, High Pressure Liquid; DNA Mutational Analysis; Denmark; Female; Genes, Recessive; Humans; Infant; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Mutation; Oxidoreductases; Pedigree; Phenotype; Prevalence; Registries; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; Tyrosine
PY - 2009
Y1 - 2009
N2 - PURPOSE: The study was initiated to investigate the mutation spectrum of four OCA genes and to calculate the birth prevalence in patients with autosomal recessive albinism. METHODS: Mutation analysis using dHPLC or direct DNA sequencing of TYR, OCA2, TYRP1, and MATP was performed in 62 patients. Furthermore, 15 patients were investigated for mutations in SLC24A5. Allele expression was investigated in heterozygous patients by RT-PCR analysis. The birth prevalence was calculated based on retrospective data from a compulsory national register. RESULTS: Sixty-two patients were investigated for mutations. Two mutations in one OCA gene explained oculocutaneous albinism (OCA) in 44% of the patients. Mutations in TYR were found in 26% of patients, while OCA2 and MATP caused OCA in 15% and 3%, respectively. No mutations were found in TYRP1. Of the remaining 56% of patients, 29% were heterozygous for a mutation in either TYR or OCA2, and 27% were without mutations in any of the four genes. Exclusive expression of the mutant allele was found in four heterozygous patients. A minimum birth prevalence of 1 in 14,000 was calculated, based on register data on 218 patients. The proportion of OCA to autosomal recessive ocular albinism (AROA) based on clinical findings was 55 to 45. CONCLUSIONS: TYR is the major OCA gene in Denmark, but several patients do not have mutations in the investigated genes. A relatively large fraction of patients were observed with AROA, and of those 52% had no mutations compared with 15% of those with OCA.
AB - PURPOSE: The study was initiated to investigate the mutation spectrum of four OCA genes and to calculate the birth prevalence in patients with autosomal recessive albinism. METHODS: Mutation analysis using dHPLC or direct DNA sequencing of TYR, OCA2, TYRP1, and MATP was performed in 62 patients. Furthermore, 15 patients were investigated for mutations in SLC24A5. Allele expression was investigated in heterozygous patients by RT-PCR analysis. The birth prevalence was calculated based on retrospective data from a compulsory national register. RESULTS: Sixty-two patients were investigated for mutations. Two mutations in one OCA gene explained oculocutaneous albinism (OCA) in 44% of the patients. Mutations in TYR were found in 26% of patients, while OCA2 and MATP caused OCA in 15% and 3%, respectively. No mutations were found in TYRP1. Of the remaining 56% of patients, 29% were heterozygous for a mutation in either TYR or OCA2, and 27% were without mutations in any of the four genes. Exclusive expression of the mutant allele was found in four heterozygous patients. A minimum birth prevalence of 1 in 14,000 was calculated, based on register data on 218 patients. The proportion of OCA to autosomal recessive ocular albinism (AROA) based on clinical findings was 55 to 45. CONCLUSIONS: TYR is the major OCA gene in Denmark, but several patients do not have mutations in the investigated genes. A relatively large fraction of patients were observed with AROA, and of those 52% had no mutations compared with 15% of those with OCA.
U2 - 10.1167/iovs.08-2639
DO - 10.1167/iovs.08-2639
M3 - Journal article
C2 - 19060277
SN - 0146-0404
VL - 50
SP - 1058
EP - 1064
JO - Investigative Ophthalmology & Visual Science
JF - Investigative Ophthalmology & Visual Science
IS - 3
ER -