A new ERBB4 variant in amyotrophic lateral sclerosis type 19: Case report and review of the literature

Amyotrophic lateral sclerosis (ALS), the most common type of motor neuron diseases (MND) in adults, is a degenerative neurological disorder involving the destruction of motor neurons, leading to progressive muscle weakness and atrophy within 3–5 years [1]. Most cases of ALS are sporadic (sALS) and about 5%−10% are familial (fALS). fALS patients presented with typical clinical features of ALS [1]. The etiology and pathogenesis of ALS remain unclear; thus, few efficient methods are available [2]. More research is needed in this regard. Up to date, more than 20 genes have been recognized to be associated with ALS [2], [3]. Among these loci, 13%−20% of fALS are associated with pathogenic variants in the SOD1 gene, and about 40% are associated with hexanucleotide repeats in the C9ORF72 gene. In addition, pathogenic variants in FUS, ANG, TARDBP, and FIG4 genes may account for up to 5%, 2%, 5%, and 3% of fALS, respectively.

ALS19, a rare form of ALS, has been proved to be an autosomal dominant inherited disease. Thus far, it has been found in only three families with onset of classic ALS. It is characterized by the involvement of both upper and lower motor neurons, without obvious cognitive dysfunction, and relatively slow progression [1]. The ERBB4 is located on 2 chromosome and encodes the ErbB4 protein. The ERBB4 mutation can reduce the autophosphorylation of ErbB4, and then be involved in the pathogenesis of ALS. Mutations in ERBB4 have been revealed as causative gene mutations of ALS19 [1], [4]. Here, we report an ALS19 case carrying a novel mutation in ERBB4 c. 1972 A>T, p. I658F.

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