Prevalence and Genetics of Leber Hereditary Optic Neuropathy in the Danish Population.

PURPOSE: In Denmark, the occurrence of Leber hereditary optic neuropathy (LHON) has continuously been monitored since 1944. We provide here a summary of 70 years of data collection including registered lines and subjects by the end of 2012. METHODS: Affected individuals were identified from a national register of hereditary eye diseases at the National Eye Clinic (NEC), a tertiary low vision rehabilitation center for the entire Danish population. The assembling of LHON pedigrees was based on the reconstruction of published families and newly diagnosed cases from 1980 to 2012 identified in the files of NEC. Genealogic follow-up on the maternal ancestry of all affected individuals was performed to identify a possible relation to an already known maternal line. A full genotypic characterization of the nation-based LHON cohort is provided. RESULTS: Forty different lines were identified. The number of live affected individuals with a verified mitochondrial DNA mutation was 104 on January 1, 2013, which translates to a prevalence rate of 1:54,000 in the Danish population. CONCLUSIONS: Haplogroup distribution as well as mutational spectrum of the Danish LHON cohort do not deviate from those of other European populations. The genealogic follow-up reveals a relatively high turnover among families with approximately 15 newly affected families per century and the dying out of earlier maternal lines.

Partial USH2A deletions contribute to Usher syndrome in Denmark.

Usher syndrome is an autosomal recessive disorder characterized by congenital hearing impairment, progressive visual loss owing to retinitis pigmentosa and in some cases vestibular dysfunction. Usher syndrome is divided into three subtypes, USH1, USH2 and USH3. Twelve loci and eleven genes have so far been identified. Duplications and deletions in PCDH15 and USH2A that lead to USH1 and USH2, respectively, have previously been identified in patients from United Kingdom, Spain and Italy. In this study, we investigate the proportion of exon deletions and duplications in PCDH15 and USH2A in 20 USH1 and 30 USH2 patients from Denmark using multiplex ligation-dependent probe amplification (MLPA). Two heterozygous deletions were identified in USH2A, but no deletions or duplications were identified in PCDH15. Next-generation mate-pair sequencing was used to identify the exact breakpoints of the two deletions identified in USH2A. Our results suggest that USH2 is caused by USH2A exon deletions in a small fraction of the patients, whereas deletions or duplications in PCDH15 might be rare in Danish Usher patients.