Identification of 11 novel mutations in USH2A among Japanese patients with Usher syndrome type 2

Abstract

Usher syndrome (USH) is an autosomal recessive disorder characterized by retinitis pigmentosa and hearing loss. USH type 2 (USH2) is the most common type of USH and is frequently caused by mutations in USH2A, which accounts for 74-90% of USH2 cases. This is the first study reporting the results of scanning for USH2A mutations in Japanese patients with USH2. In 8 of 10 unrelated patients, we identified 14 different mutations. Of these mutations, 11 were novel. Although the mutation spectrum that we identified differed from that for Caucasians, the incidence of mutations in USH2A was 80% for all patients tested, which is consistent with previous findings. Further, c.8559-2A>G was identified in four patients and accounted for 26.7% of mutated alleles; it is thus a frequent mutation in Japanese patients. Hence, mutation screening for c.8559-2A>G in USH2A may prove very effective for the early diagnosis of USH2.

The USH2A c.2299delG mutation: dating its common origin in a Southern European population

“…This mutation was found in isolated patients of Chinese origin. 15 The recent studies carried out by Dai et al 12 in China and Nakanishi et al 13 in Japan indicate that c.2299delG is not common among Asian USH2 patients, although the authors only screened 6 and 10 patients, respectively. Further studies are needed to investigate the frequency of c.2299delG in this and other non-European populations.…”

Frecuencia de mutaciones en el gen de la usherina (USH2A) en 26 individuos colombianos con síndrome de Usher, tipo II

“…Se ha reportado que la distribución de esta mutación varía geográficamente en Europa, disminuyendo de norte a sur (29), de ahí que se identifique en mayor frecuencia en países del norte, como Escandinavia, que en países del sur, como Francia y España. En población japonesa su frecuencia es baja (30).…”

“…Un análisis posterior de la isoforma larga del gen permitirá conocer nuevas mutaciones en estos individuos y genotipificar a una mayor proporción de la población, ya que se ha reportado que esta isoforma puede albergar incluso más mutaciones que la isoforma corta (26,27,30,31). Se ha propuesto la técnica de microarrays como un método de genotipificación rápido y efectivo (32), pero, para poder llevarlo a cabo, es necesario tener una mejor idea de las mutaciones propias de población colombiana.…”

Usher Syndrome: Genes, Proteins, Models, Molecular Mechanisms, and Therapies

“…USH2A is the most predominant causative gene in all USHs among different human ethnic populations (Eudy et al, 1998;Dreyer et al, 2000;Weston et al, 2000;Aller et al, 2004;van Wijk et al, 2004;Adato et al, 2005a;Hartong et al, 2006;Baux et al, 2007;Kaiserman et al, 2007;Dreyer et al, 2008;Nakanishi et al, 2009;Yan et al, 2009;McGee et al, 2010). Its mutations lead to a wide spectrum of vision and hearing defects in patients.…”