PFN1 mutations are also rare in the Catalan population with amyotrophic lateral sclerosis

Abstract

Evidence of genetic heterogeneity in ALS has been found, with at least 31 genes being identified to date as causing ALS, and other genes being suggested as risk factors for susceptibility to the disease and for phenotype modifications. In recent years, new molecular genetic methodologies, especially GWAS and exome sequencing, have contributed to the identification of new ALS genes. Some of these genes (SOD1, TARDBP, FUS, and C9orf72) have homogenous frequencies in different populations. However, a few genes are rare in populations other than those in which they were first identified. Here we investigate the frequency of the PFN1 gene in a Catalan ALS population. A mutational analysis of the PFN1 gene was carried out on a Catalan cohort of 42 ALS families (FALS) and 423 sporadic ALS patients (SALS). The screening included 600 healthy controls. No PFN1 mutations were identified in either the FALS or SALS group. We also found no mutations in the control group. Our results are consistent with those described in other populations with very low frequencies, suggesting that PFN1 is a very rare cause of ALS worldwide. Together with the absence of a distinctive phenotype associated with ALS18, these results mean that this gene should be a second or third line for inclusion in screening in patients requesting genetic counseling.

Recent advances in amyotrophic lateral sclerosis

“…PFN1 mutations were initially identified using an exome-sequencing approach in 2.6 % of FALS cases [ 45 ]. A mutational analysis of the PFN1 gene was carried out in a Catalan cohort of 42 FALS and 423 SALS patients [ 47 ]. No PFN1 mutations were identified.…”

Familial flail leg ALS caused by PFN1 mutation

“…Further sequencing identified four missense mutations (p.C71G, p.M114T, p.E117G and p.G118V) in 7 out of 274 FALS cases (2.6%) 4. Subsequent 11 studies screening mutations in PFN1 gene in ALS populations5–15 have identified only three novel mutations: A20T mutation in a patient of Middle Eastern ethnicity with FALS (0.5%),5 T109M mutation in a German FALS case (0.9%)6 and R136W mutation in a Chinese SALS case (0.2%). 7 Together with a previous cohort,8 no PFN1 mutations were identified in 35 FALS indexes and 599 SALS cases of Chinese origin.…”