A novel MERTK deletion is a common founder mutation in the Faroe Islands and is responsible for a high proportion of retinitis pigmentosa cases

作者：Ostergaard Elsebet^*; Duno Morten; Batbayli Mustafa; Vilhelmsen Kaj; Rosenberg Thomas

来源：Molecular Vision, 2011, 17(167): 1485-1492.

Purpose: The aim of the study was to elucidate the genetic background of retinitis pigmentosa (RP) in a Faroe Islands population, a genetic isolate in the North Atlantic Ocean.
Methods: Blood samples were collected from subjects diagnosed with RP and their families. DNA from affected individuals underwent single nucleotide polymorphism microarray analysis and homozygosity mapping followed by sequence analysis of candidate genes.
Results: We identified 25 cases of nonsyndromic RP corresponding to a prevalence of 1 in 1,900. Single nucleotide polymorphism analysis revealed a homozygous region on chromosome 2q, common to patients in four families, which harbored the RP gene MER tyrosine kinase protooncogene (MERTK). A deletion of 91 kb was identified in seven patients, representing 30% of the analyzed Faroese cases of nonsyndromic RP. The clinical course of six patients who were homozygous for the deletion showed onset in the first decade followed by a rapid deterioration of both rod and cone photoreceptor function. Early macular involvement was present, in accordance with that of other reported patients with MERTK mutations.
Conclusions: Previous studies have shown a frequency of less than 1% of MERTK mutations in RP patients. The 91-kb deletion encompassing exons 1-7 of MERTK is a common founder mutation in the Faroe Islands, responsible for around 30% of RP, and together with mutations in protocadherin 21 (PCDH21) accounts for more than half of the retinal dystrophy cases.

• 出版日期2011-6-4