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Brown-Vialetto-Van Laere(BVVL) and Fazio-Londe(FL) are disorders with ALS-like features, usually with recessive inheritance. We aimed to identify causative mutations in ten probands. Neurological examinations, genetic analysis, audiometry, MRI, biochemical and immunological testings, and/or muscle histopathology were performed. Mutations in known causative gene SLC52A3 were found in seven probands. More importantly, only one mutated allele was observed in several patients, and variable expressivity and incomplete penetrance were clearly noted. Environmental insults may contribute to variable presentations. Putative causative mutations in other genes were identified in three probands. Two of the genes, WDFY4 and TNFSF13B, have immune related functions. Inflammatory responses were implicated in the patient with the WDFY4 mutation. Malfunction of the immune system and mitochondrial anomalies were shown in the patient with the TNFSF13B mutation. Prevalence of heterozygous SLC52A3 BVVL causative mutations and notable variability in expressivity of homozygous and heterozygous genotypes are being reported for the first time.Identification of WDFY4 and TNFSF13B as candidate causative genes supports conjectures on involvement of the immune system in BVVL and ALS.

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