Birth prevalence and mutation spectrum in danish patients with autosomal recessive albinism.
OBJECTIVE
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.
Grønskov
Karen
K
edical Genetics Laboratory Center, Kennedy Center, Glostrup, Denmark. kag@kennedy.dk
Ek
Jakob
J
Sand
Annie
A
Scheller
Rudolf
R
Bygum
Anette
A
Brixen
Kim
K
Brondum-Nielsen
Karen
K
Rosenberg
Thomas
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D016115:Albinism, Oculocutaneous / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D000483:Alleles; D000951:Antigens, Neoplasm / Q000235:genetics*; D017920:Antiporters / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D007223:Infant; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D015995:Prevalence; D012042:Registries; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014443:Tyrosine / Q000235:genetics*
D000951:Antigens, Neoplasm; D017920:Antiporters; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C489600:OCA2 protein, human; C506584:SLC24A5 protein, human; C510061:SLC45A2 protein, human; D014443:Tyrosine; D010088:Oxidoreductases; C489799:TYRP1 protein, human