The p.P56S mutation in the VAPB gene is not due to a single founder: The first European case

A dominant missense mutation p.P56S in the vesicle associated membrane protein associated protein B (VAPB) gene was described in eight Brazilian families of Portuguese descent showing a wide spectrum of motor neuron diseases (MNDs) including spinal muscular atrophy (SMA) and familial amyotrophic lateral sclerosis (ALS) (ALS8) 1, 2. Haplotype analysis indicated a common ancestor with a founding event 23 generations previously, when this ancestor was still living in Portugal 3. We report the first identification of the p.P56S mutation in the VAPB gene in a non‐Brazilian patient.

A 43‐year‐old man (III‐1) showed slowly progressive muscular weakness for 2 years and a family history of autosomal dominant neuromuscular disease through at least three generations (Fig 1). The patient's mother (II‐1) suffered from slowly progressive muscular weakness over 30 years. No pyramidal tract signs had been observed. She was wheelchair bound 20 years after onset and died at the age of 67. The maternal grandfather (I‐1) had a history of progressive muscular weakness, had died aged 57 and had six siblings. Three (I‐5, I‐6, I‐7) suffered from muscular weakness. One cousin of the patient's mother (II‐2) was diagnosed with SMA. There was no family record of Portuguese or Brazilian ancestors in at least four previous generations. All family members originated from northern Germany.