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• A response to "SOD1, ANG, VAPB, TARDBP, and FUS mutations in familial amyotrophic lateral: genotype - phenotype correlations"
  Miguel Mitne-Neto
  Published on: 27 April 2016

• Published on: 27 April 2016

  A response to "SOD1, ANG, VAPB, TARDBP, and FUS mutations in familial amyotrophic lateral: genotype - phenotype correlations"

  • Miguel Mitne-Neto, PhD Candidate

  Dr. Constantin Polychronakos, Editor Journal of Medical Genetics Dear Dr. Polychronakos We read with great interest the recent publication from your journal entitled "SOD1, ANG, VAPB, TARDBP, and FUS mutations in familial amyotrophic lateral: genotype - phenotype correlations" Millecamps S., Salachas F., Cazeneuve C., et al. J Med Genet published online June 24, 2010 doi: 10.1136/jmg.2010.077180. This manuscript brings re...

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  Dr. Constantin Polychronakos, Editor Journal of Medical Genetics Dear Dr. Polychronakos We read with great interest the recent publication from your journal entitled "SOD1, ANG, VAPB, TARDBP, and FUS mutations in familial amyotrophic lateral: genotype - phenotype correlations" Millecamps S., Salachas F., Cazeneuve C., et al. J Med Genet published online June 24, 2010 doi: 10.1136/jmg.2010.077180. This manuscript brings relevant information about the mutation frequencies and genotype-phenotype data regarding the main genes responsible for the familial forms of ALS (FALS). Additionally, as well pointed by the authors, this study is the first large scale evaluation of FALS in the French population. However, we would like to call the authors attention for two important aspects: 1) According to the authors "...The P56S carrier was of Japanese descent, and represents the first non-Brazilian patient carrying this mutation...". The ALS8 form was first mapped at 20q13 in a large Brazilian family in 2004, which was published in the Journal of Medical Genetics (Nishimura et al., 2004A). Later in the same year, the c.166C-T / p.Pro56Ser mutation in the VAPB gene was identified in this and six other families (Nishimura et al., 2004B) as responsible for this disorder. Additionally, microsatellites analyses around VAPB showed that these families share a common haplotype. It suggests a founder effect estimated to have occurred about 500 years ago, concomitant with Brazilian colonization by Portugal (Nishimura et al., 2005). Recently, in collaboration with our group, Funke et al. (2010) identified a German ALS8 patient, with no family record of Brazilian or Portuguese ancestry, carrying the c.166C-T mutation in VAPB, which showed that ALS8 is no more restricted to Brazil. Therefore, this German patient comprises the first case of an ALS8 patient out of Brazil and this should be corrected in Millecamps et al., MS. 2) The German patient, identified by Funke et al. (2010), carries an haplotype which is different from the one found in the Brazilian ALS8 families. This suggests that the c.166C-T (P56S) mutation is not due to the same founder and that, probably, it happened at least in two independent events. Millecamps et al., (2010) claims that "...The finding of a P56S VAPB mutation in a patient of Japanese origin presumably reflects the Portuguese trading connection with the Far East and Brazil in the mid 16th century..." suggesting that the Japanese and the Brazilian families could share the same genomic region. However, they do not show such haplotype analysis or present any historical evidence for this supposition. We believe that such information is relevant for the researchers in the ALS field and for this reason an erratum should be considered in order to ensure the best information to the readers of the Journal of Medical Genetics . We appreciate your attention Sincerely Miguel Mitne-Neto PhD Candidate Human Genome Research Center University of Sao Paulo References Mayana Zatz Professor of Genetics Director- Human Genome Research Center University of Sao Paulo President-Brazilian Muscular Dystrophy Association [A] Nishimura A.L., Mitne-Neto M., Silva H.C.A., Oliveira J.R.M., Vainzof M., Zatz M. (2004) "A novel locus for late onset amyotrophic lateral sclerosis/motor neurone disease variant at 20q13" J Med Genet. 41, 315-320 [B] Nishimura A.L., Mitne-Neto M., Silva H.C., Richieri-Costa A., Middleton S., Cascio D., Kok F., Oliveira J.R., Gillingwater T., Webb J., Skehel P., Zatz M. (2004). A mutation in the vesicle- trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am J Hum Genet 75, 822-31 Nishimura A.L., Al-Chalabi A., Zatz M. (2005). A common founder for amyotrophic lateral sclerosis type 8 (ALS8) in the Brazilian population. Hum Genet 118, 499- 500 Funke A.D., Esser M., Kruttgen A., Weis J., Mitne-Neto M., Lazar M., Nishimura A.L., Sperfeld A.D., Trillenberg P., Senderek J., Krasnianski M., Zatz M., Zierz S., Deschauer M. (2010) The p.P56S mutation in the VAPB gene is not due to a single founder: the first European case. Clin Genet 77, 302-303 Millecamps S., Salachas F., Cazeneuve C., et al. "SOD1, ANG, VAPB, TARDBP, and FUS mutations in familial amyotrophic lateral: genotype - phenotype correlations" (2010) J Med Genet published online June 24, 2010 doi: 10.1136/jmg.2010.077180.

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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