Recessive PYROXD1 mutations cause adult-onset limb-girdle-type muscular dystrophy

• DOI: 10.1007/s00415-018-9137-8
• Publication Date: 2018-12-04T05:37:42Z
• Authors: Markus T. Sainio; Salla Välipakka; Bruno Rinaldi; Helena Lapatto; Anders Paetau; Simo Ojanen; Virginia Brilhante; Manu Jokela; Sanna Huovinen; Mari Auranen; Johanna Palmio; Sylvie Friant; Emil Ylikallio; Bjarne Udd; Henna Tyynismaa
• Keywords: Limb-girdle muscular dystrophy; Proximal muscle weakness

To describe adult-onset limb-girdle-type muscular dystrophy caused by biallelic variants in the PYROXD1 gene, which has been recently linked to early-onset congenital myofibrillar myopathy.Whole exome sequencing was performed for neuromuscular disease patients with no molecular diagnosis. Patients underwent clinical characterization, lower limb muscle MRI, biopsy and spirometry. A yeast complementation assay used determine biochemical consequences of genetic variants.We identified four variants. Three patients, who had symptom onset their 20s or 30s, were homozygous previously described p.Asn155Ser. The fourth patient, at age 49, compound heterozygous p.Asn155Ser variant unknown p.Tyr354Cys. All presented a LGMD-type phenotype symmetric weakness wasting. Symptoms started proximal muscles limbs, progressed slowly involve also upper limbs proximal-predominant fashion. remained ambulant past 60. They restrictive lung but cardiac impairment. Muscle MRI showed strong involvement anterolateral thigh muscles. displayed chronic myopathic changes. Yeast demonstrated p.Tyr354Cys mutation impair oxidoreductase ability.PYROXD1 can cause an progressive phenotype.