Point mutations in the PABPN1 gene in OPMD are no longer the domain of Europe

Oculopharyngeal muscular dystrophy (OPMD) is a muscular disease of very late onset, most often after the age of fifty, and which mainly results in slowly progressive damage to the muscles of the eyelids, face, pharynx and pelvic girdle. Inherited in an autosomal dominantEn génétique, c’est la caractéristique d’un individu qui n’a besoin que d’un seul exemplaire d’un certain gène (allèle) pour s’exprimer. Cet exemplaire unique peut venir du père ou de la mère. mode, it is found on all continents with several clusters identified in Quebec and Israel. The clinical diagnosis is confirmed by a genetic test which in the vast majority of cases shows an expansion of GCA or GCG triplets in the PABPN1 gene located on chromosomeForme que prend l’ADN pendant la division cellulaire (aspect de fins bâtonnets). Il est composé de 2 bras, un bras long et un bras court. Par convention, le bras long s’appelle q, et le bras court s’appelle p. Chez l’être humain, il y a 23 paires de chromosomes (soit 46 chromosomes). Vingt-deux paires sont constituées de 2 chromosomes identiques, appelés autosomes. La vingt-troisième paire est constituée des chromosomes sexuels, XX chez la femme et XY chez l’homme. 14. 

In an article published in July 2021, Japanese clinicians report the observation of a 78-year-old female patient with all the clinical features of OPMD, whose routine genetic test was negative. In the absence of the expected trinucleotide repeat, it was decided to sequence the entire PABPN1 gene, which revealed a point mutationModification soudaine et transmissible du matériel génétique. Elle peut être spontanée ou induite par des agents dits » mutagènes » (radiations, produits toxiques,…). (c.35G> C). This unusual pathological sequence variation had previously been reported in three English patients, which suggested the existence of a founder effect in Europe. This same mutation is at the origin of the replacement of a glycine in alanine in position 12. From a functional point of view, this results in an elongation of polyalanine residues comparable to that observed in the forms of OPMD with classical genotype. 

A Japanese case of oculopharyngeal muscular dystrophy (OPMD) with PABPN1 c.35G > C; p.Gly12Ala point mutation. Nishii YS, Noto YI, Yasuda R et al. BMC Neurol. 2021 (Juil). 21(1):265.