Identification of novel variations of oculocutaneous albinism type 2 with Prader-Willi syndrome/Angelman syndrome in two Chinese families.

Oculocutaneous albinism (OCA) is an autosomal recessive disorder caused by a variety of genomic variations. Our aim is to identify the molecular basis of OCA in two families and lay the foundation for prenatal diagnosis. Four types of OCA-causing mutations in the TYR, , TYRP1, or SLC45A2 genes were screened. Linkage analysis was performed because the mutations found in the gene violated the laws of classical Mendelian heredity. Primer-walking sequencing combined with microsatellite and single-nucleotide polymorphism analysis was used to ascertain deletion ranges. Bioinformatics methods were used to assess the pathogenicity of the new mutations. Proband 1 was diagnosed as OCA2 with Prader-Willi syndrome (PWS) due to a novel atypical paternal deletion (chromosome 15: 22330347-26089649) and a pathogenic mutation, c.1327G>A (Val443Ile), in the gene of the maternal chromosome. The prenatal diagnosis results for family 1 indicated the fetus was a heterozygous carrier (c.1327G>A in the gene) with a normal phenotype. Proband 2 was diagnosed as OCA2 with Angelman syndrome (AS) due to a typical maternal deletion of chromosome 15q11-q13 and a novel mutation, c.1514T>C (Phe505Ser), in the gene of the paternal chromosome. This novel mutation c.1514T>C (Phe505Ser) in the gene was predicted as a pathogenic mutation. Our study has shown clear genotype-phenotype correlations in patients affected by distinct deletions of the PWS or AS region and missense mutations in the gene. Our results have enriched the mutation spectrum of albinism diseases and provided insights for more accurate diagnosis and genetic counseling.