Abstract
Amyotrophic Lateral Sclerosis and CHARGE syndrome are complex neurological disorders, which never occurred together in the same family and, to date, no putative correlation between them has been described on PubMed Central. Due to our aim was to evaluate the presence of different genetic variants involved in these pathologies, we reported a clinical and genetic description of two sisters affected by these two different disorders. In the CHARGE patient, molecular analysis of the CHD7 gene revealed the c.8016G >A de novo variant in exon 37. The ALS patient had been screened negative for mutations in SOD1, TARDBP, FUS/TLS, C9orf72 and KIF5A genes. Anyway, targeted next generation sequencing analysis identified known and unknown genetic variations in 39 ALS-related genes: a total of 380 variants were reported, of which 194 in the ALS patient and 186 in the CHARGE patient. To date, although the results suggest that the occurrence of the two syndromes in the same family is co-incidental rather than based on a causative genetic variant, we could hypothesize that other factors might act as modulators in the pathogenesis of these different phenotypes.
Highlights
Recent findings in the field of molecular biology have led to significant advances in our understanding of the genetic basis of a number of rare disorders
Due to our aim was to evaluate the presence of different genetic variants involved in these pathologies, we reported a clinical and genetic study of a family from South of Italy composed of parents and two daughters affected by amyotrophic lateral sclerosis (ALS) and CHARGE syndrome, respectively
According to the applied filtering strategy and taking into account the CHD7 mutation found in the CHARGE patient, we focused on unshared variations reported in Supplementary Table B
Summary
Recent findings in the field of molecular biology have led to significant advances in our understanding of the genetic basis of a number of rare disorders. Most of the neurological diseases have well-established evidence of genetic contributions [1, 2]. We focused on two complex neurological disorders, amyotrophic lateral sclerosis (ALS) and CHARGE syndrome, whereas until now, CHARGE association and ALS disease never occurred together in the same family and no cases have been reported. The acronym CHARGE was coined in 1981 by Pagon et al [3], for designing a phenotypically variable, multiorgan genetic disorder, first described in 1979 by Hall et al [4] involving six cardinal features: ocular colobomas, heart malformation, atresia of the choanae, retardation of growth and/or development, genital abnormalities and ear anomalies with hearing loss [3]. Several investigators have suggested that CHARGE syndrome may reflect a polytrophic
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