Skip to main content
Top
Published in: Neurological Sciences 5/2021

Open Access 01-05-2021 | Spastic Paraplegia | Brief Communication

ALS2-related disorders in Spanish children

Authors: Enrique Nogueira, Juana Alarcón, Carmen Garma, Cecilia Paredes

Published in: Neurological Sciences | Issue 5/2021

Login to get access

Abstract

ALS2 gene encoding for alsin protein is responsible for neurological disorders due to retrograde degeneration of the upper motor neurons of the pyramidal tracts, inherited in an autosomal recessive manner, and displaying a clinical continuum including the infantile ascending hereditary spastic paraplegiaidentified in three Spanish children presented here.
Literature
2.
go back to reference Brugman F, Eymard-Pierre E, van den Berg LH et al (2007) Adult-onset primary lateral sclerosis is not associated with mutations in the ALS2 gene. Neurology 69:702–704CrossRef Brugman F, Eymard-Pierre E, van den Berg LH et al (2007) Adult-onset primary lateral sclerosis is not associated with mutations in the ALS2 gene. Neurology 69:702–704CrossRef
3.
go back to reference Hadano S, Hand CK, Osuga H, Yanagisawa Y, Otomo A, Devon RS, Miyamoto N, Showguchi-Miyata J, Okada Y, Singaraja R, Figlewicz DA, Kwiatkowski T, Hosler BA, Sagie T, Skaug J, Nasir J, Brown RH Jr, Scherer SW, Rouleau GA, Hayden MR, Ikeda JE (2001) A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2. Nat Genet 29:166–173CrossRef Hadano S, Hand CK, Osuga H, Yanagisawa Y, Otomo A, Devon RS, Miyamoto N, Showguchi-Miyata J, Okada Y, Singaraja R, Figlewicz DA, Kwiatkowski T, Hosler BA, Sagie T, Skaug J, Nasir J, Brown RH Jr, Scherer SW, Rouleau GA, Hayden MR, Ikeda JE (2001) A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2. Nat Genet 29:166–173CrossRef
4.
go back to reference Yang Y, Hentati A, Deng HX, Dabbagh O, Sasaki T, Hirano M, Hung WY, Ouahchi K, Yan J, Azim AC, Cole N, Gascon G, Yagmour A, Ben-Hamida M, Pericak-Vance M, Hentati F, Siddique T (2001) The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. Nat Genet 29:160–165CrossRef Yang Y, Hentati A, Deng HX, Dabbagh O, Sasaki T, Hirano M, Hung WY, Ouahchi K, Yan J, Azim AC, Cole N, Gascon G, Yagmour A, Ben-Hamida M, Pericak-Vance M, Hentati F, Siddique T (2001) The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. Nat Genet 29:160–165CrossRef
5.
go back to reference Eymard-Pierre E, Lesca G, Dollet S, Santorelli FM, di Capua M, Bertini E, Boespflug-Tanguy O (2002) Infantile-onset ascending hereditary spastic paralysis is associated with mutations in the alsin gene. Am J Hum Genet 71:518–527CrossRef Eymard-Pierre E, Lesca G, Dollet S, Santorelli FM, di Capua M, Bertini E, Boespflug-Tanguy O (2002) Infantile-onset ascending hereditary spastic paralysis is associated with mutations in the alsin gene. Am J Hum Genet 71:518–527CrossRef
6.
go back to reference Devon RS, Helm JR, Rouleau GA, Leitner Y, Lerman-Sagie T, Lev D, Hayden MR (2003) The first nonsense mutation in alsin results in a homogeneous phenotype of infantile-onset ascending spastic paralysis with bulbar involvement in two siblings. Clin Genet 64:210–215CrossRef Devon RS, Helm JR, Rouleau GA, Leitner Y, Lerman-Sagie T, Lev D, Hayden MR (2003) The first nonsense mutation in alsin results in a homogeneous phenotype of infantile-onset ascending spastic paralysis with bulbar involvement in two siblings. Clin Genet 64:210–215CrossRef
7.
go back to reference Gros-Louis F, Meijer IA, Hand CK, Dubé MP, MacGregor DL, Seni MH, Devon RS, Hayden MR, Andermann F, Andermann E, Rouleau GA (2003) An ALS2 gene mutation causes hereditary spastic paraplegia in a Pakistani kindred. Ann Neurol 53:144–145CrossRef Gros-Louis F, Meijer IA, Hand CK, Dubé MP, MacGregor DL, Seni MH, Devon RS, Hayden MR, Andermann F, Andermann E, Rouleau GA (2003) An ALS2 gene mutation causes hereditary spastic paraplegia in a Pakistani kindred. Ann Neurol 53:144–145CrossRef
8.
go back to reference Kress JA, Kühnlein P, Winter P, Ludolph AC, Kassubek J, Müller U, Sperfeld AD (2005) Novel mutation in the ALS2 gene in juvenile amyotrophic lateral sclerosis. Ann Neurol 58:800–803CrossRef Kress JA, Kühnlein P, Winter P, Ludolph AC, Kassubek J, Müller U, Sperfeld AD (2005) Novel mutation in the ALS2 gene in juvenile amyotrophic lateral sclerosis. Ann Neurol 58:800–803CrossRef
9.
go back to reference Eymard-Pierre E, Yamanaka K, Haeussler M, Kress W, Gauthier-Barichard F, Combes P, Cleveland DW, Boespflug-Tanguy O (2006) Novel missense mutation in ALS2 gene results in infantile ascending hereditary spastic paralysis. Ann Neurol 59:976–980CrossRef Eymard-Pierre E, Yamanaka K, Haeussler M, Kress W, Gauthier-Barichard F, Combes P, Cleveland DW, Boespflug-Tanguy O (2006) Novel missense mutation in ALS2 gene results in infantile ascending hereditary spastic paralysis. Ann Neurol 59:976–980CrossRef
10.
go back to reference Panzeri C, De Palma C, Martinuzzi A et al (2006) The first ALS2 missense mutation associated with JPLS reveals new aspects of alsin biological function. Brain 129:1710–1719CrossRef Panzeri C, De Palma C, Martinuzzi A et al (2006) The first ALS2 missense mutation associated with JPLS reveals new aspects of alsin biological function. Brain 129:1710–1719CrossRef
11.
go back to reference Sztriha L, Panzeri C, Kálmánchey R, Szabó N, Endreffy E, Túri S, Baschirotto C, Bresolin N, Vekerdy Z, Bassi MT (2008) First case of compound heterozygosity in ALS2 gene in infantile-onset ascending spastic paralysis with bulbar involvement. Clin Genet 73:591–593CrossRef Sztriha L, Panzeri C, Kálmánchey R, Szabó N, Endreffy E, Túri S, Baschirotto C, Bresolin N, Vekerdy Z, Bassi MT (2008) First case of compound heterozygosity in ALS2 gene in infantile-onset ascending spastic paralysis with bulbar involvement. Clin Genet 73:591–593CrossRef
12.
go back to reference Verschuuren-Bemelmans CC, Winter P, Sival DA, Elting JW, Brouwer OF, Müller U (2008) Novel homozygous ALS2 nonsense mutation (p.Gln715X) in sibs with infantile-onset ascending spastic paralysis: the first cases from northwestern Europe. Eur J Hum Genet 16:1407–1411CrossRef Verschuuren-Bemelmans CC, Winter P, Sival DA, Elting JW, Brouwer OF, Müller U (2008) Novel homozygous ALS2 nonsense mutation (p.Gln715X) in sibs with infantile-onset ascending spastic paralysis: the first cases from northwestern Europe. Eur J Hum Genet 16:1407–1411CrossRef
13.
go back to reference Mintchev N, Zamba-Papanicolaou E, Kleopa KA, Christodoulou K (2009) A novel ALS2 splice-site mutation in a Cypriot juvenile-onset primary lateral sclerosis family. Neurology 72:28–32CrossRef Mintchev N, Zamba-Papanicolaou E, Kleopa KA, Christodoulou K (2009) A novel ALS2 splice-site mutation in a Cypriot juvenile-onset primary lateral sclerosis family. Neurology 72:28–32CrossRef
14.
go back to reference Shirakawa K, Suzuki H, Ito M, Kono S, Uchiyama T, Ohashi T, Miyajima H (2009) Novel compound heterozygous als2 mutations cause juvenile amyotrophic lateral sclerosis in Japan. Neurology 73:2124–2126CrossRef Shirakawa K, Suzuki H, Ito M, Kono S, Uchiyama T, Ohashi T, Miyajima H (2009) Novel compound heterozygous als2 mutations cause juvenile amyotrophic lateral sclerosis in Japan. Neurology 73:2124–2126CrossRef
15.
go back to reference Luigetti M, Lattante S, Conte A, Romano A, Zollino M, Marangi G, Sabatelli M (2013) A novel compound heterozygous ALS2 mutation in two Italian siblings with juvenile amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 14:470–472CrossRef Luigetti M, Lattante S, Conte A, Romano A, Zollino M, Marangi G, Sabatelli M (2013) A novel compound heterozygous ALS2 mutation in two Italian siblings with juvenile amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 14:470–472CrossRef
16.
go back to reference Flor-de-Lima F, Sampaio M, Nahavandi N (2014) Alsin related disorders: literature review and case study with novel mutations. Case Rep Genet 2014:691515PubMedPubMedCentral Flor-de-Lima F, Sampaio M, Nahavandi N (2014) Alsin related disorders: literature review and case study with novel mutations. Case Rep Genet 2014:691515PubMedPubMedCentral
17.
go back to reference Siddiqi S, Foo JN, Vu A, Azim S, Silver DL, Mansoor A, Tay SKH, Abbasi S, Hashmi AH, Janjua J, Khalid S, Tai ES, Yeo GW, Khor CC (2014) A novel splice-site mutation in ALS2 establishes the diagnosis of juvenile amyotrophic lateral sclerosis in a family with early onset anarthria and generalized dystonias. PLoS One 9:e113258CrossRef Siddiqi S, Foo JN, Vu A, Azim S, Silver DL, Mansoor A, Tay SKH, Abbasi S, Hashmi AH, Janjua J, Khalid S, Tai ES, Yeo GW, Khor CC (2014) A novel splice-site mutation in ALS2 establishes the diagnosis of juvenile amyotrophic lateral sclerosis in a family with early onset anarthria and generalized dystonias. PLoS One 9:e113258CrossRef
18.
go back to reference Xie F, Cen ZD, Xiao JF, Luo W (2015) Novel compound heterozygous ALS2 mutations in two Chinese siblings with infantile ascending hereditary spastic paralysis. Neurol Sci 36:1279–1280CrossRef Xie F, Cen ZD, Xiao JF, Luo W (2015) Novel compound heterozygous ALS2 mutations in two Chinese siblings with infantile ascending hereditary spastic paralysis. Neurol Sci 36:1279–1280CrossRef
19.
go back to reference Tariq H, Mukhtar S, Naz S (2017) A novel mutation in ALS2 associated with severe and progressive infantile onset of spastic paralysis. J Neurogenet 31:26–29CrossRef Tariq H, Mukhtar S, Naz S (2017) A novel mutation in ALS2 associated with severe and progressive infantile onset of spastic paralysis. J Neurogenet 31:26–29CrossRef
20.
go back to reference Helal M, Mazaheri N, Shalbafan B, Malamiri RA, Dilaver N, Buchert R, Mohammadiasl J, Golchin N, Sedaghat A, Mehrjardi MYV, Haack TB, Riess O, Chung WK, Galehdari H, Shariati G, Maroofian R (2018) Clinical presentation and natural history of infantile-onset ascending spastic paralysis from three families with an ALS2 founder variant. Neurol Sci 39:1917–1925CrossRef Helal M, Mazaheri N, Shalbafan B, Malamiri RA, Dilaver N, Buchert R, Mohammadiasl J, Golchin N, Sedaghat A, Mehrjardi MYV, Haack TB, Riess O, Chung WK, Galehdari H, Shariati G, Maroofian R (2018) Clinical presentation and natural history of infantile-onset ascending spastic paralysis from three families with an ALS2 founder variant. Neurol Sci 39:1917–1925CrossRef
21.
go back to reference Sato K, Otomo A, Ueda MT, Hiratsuka Y, Suzuki-Utsunomiya K, Sugiyama J, Murakoshi S, Mitsui S, Ono S, Nakagawa S, Shang HF, Hadano S (2018) Altered oligomeric states in pathogenic ALS2 variants associated with juvenile motor neuron diseases cause loss of ALS2-mediated endosomal function. J Biol Chem 293:17135–17153CrossRef Sato K, Otomo A, Ueda MT, Hiratsuka Y, Suzuki-Utsunomiya K, Sugiyama J, Murakoshi S, Mitsui S, Ono S, Nakagawa S, Shang HF, Hadano S (2018) Altered oligomeric states in pathogenic ALS2 variants associated with juvenile motor neuron diseases cause loss of ALS2-mediated endosomal function. J Biol Chem 293:17135–17153CrossRef
Metadata
Title
ALS2-related disorders in Spanish children
Authors
Enrique Nogueira
Juana Alarcón
Carmen Garma
Cecilia Paredes
Publication date
01-05-2021
Publisher
Springer International Publishing
Published in
Neurological Sciences / Issue 5/2021
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-020-04899-0

Other articles of this Issue 5/2021

Neurological Sciences 5/2021 Go to the issue