SOD1, ANG, VAPB, TARDBP, and FUS mutations in familial amyotrophic lateral sclerosis: genotype-phenotype correlations

Abstract

This study identifies new genetic associations with ALS and provides phenotype-genotype correlations with both previously reported and novel mutations.

Familial adult spinal muscular atrophy associated with the VAPB gene: report of 42 cases in Brazil

“…The maximum multipoint logarithmic odds (LOD) score was 7.45 and was found close to marker D20S164. Mutation screening of candidate genes excluded the ca thepsin Z (CTSZ), syntaxin 16 (STX 16), ATP synthase, epsilon subunit (ATP5E), and tubulin b1 (TUBB1) genes 5,6 . It is notable that they found a polymorphism in the 3_UTR of the TUBB1 gene, which was present in almost all patients but not in Brazilian normal controls.…”

Genetics of Amyotrophic Lateral Sclerosis

“…Sequencing of the gene encoding this protein (TARDBP) identified mutations in ALS patients (Kabashi et al, 2008;Shreedharan et al, 2008). To date over 40 mutations in TARDBP have been identified in several different populations with a frequency of ~5% of fALS cases and up to 2% of sALS cases Iida et al, 2010;Millecamps et al, 2010;Ticozzi et al, 2009;Van Deerlin et al, 2008). TARDBP mutations have also been observed in ALS-FTD and FTD patients (Benajiba et al, 2009;Gitcho et al, 2009b (Buratti and Baralle, 2010).…”

“…An obligate carrier did not develop the disease suggesting incomplete penetrance. Two ANG mutations (K17I and K54E) were identified in two fALS cases from France who also had a mutation in FUS (Millecamps et al, 2010). An R145C mutation has been observed in a sALS patient with a G93D SOD1 mutation (Luigetti et al, 2011).…”

Genetics of Familial Amyotrophic Lateral Sclerosis

“…Furthermore, drosophila and yeast models demonstrate FUS toxicity is due to accumulation of mutant protein in the cytoplasm (Kryndushkin et al 2011;Lanson et al 2011 (Nishimura et al 2004). This exon 2 variant has since been detected in 22 additional individuals from six Brazilian pedigrees in which there is evidence of a founder effect, although it has also been seen in a Japanese and European case (Funke et al 2010;Landers et al 2008;Millecamps et al 2010).…”