{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:18Z","timestamp":1753869678849,"version":"3.41.2"},"reference-count":15,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T00:00:00Z","timestamp":1589846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Metachromatic Leukodystrophy (MLD, OMIM 250100) is a neurodegenerative disease caused by mutations in the <jats:italic>ARSA<\/jats:italic> gene (OMIM 607574) that lead to deficiency in Arylsulfatase A (ASA). ASA pseudodeficiency (PD\u2010ASA) is a biochemical condition that substantially diminishes ASA activity but is not associated with clinical manifestations. PD\u2010ASA is associated with the c.1055A&gt;G (p.Asn352Ser) (rs2071421) and c.*96A&gt;G (rs6151429) variants, which have an estimated frequency of 2% in the population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine the activity of Arylsulfatase A and to identify variants and haplotypes in the <jats:italic>ARSA<\/jats:italic> gene in Mexican individuals with pseudodeficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two\u2010hundred apparently healthy individuals were included to determine the enzymatic activity of ASA in leukocytes by spectrophotometric analysis, and identification of the PD\u2010ASA alleles was performed by PCR\u2010RFLP assays. Genotypes were confirmed by semi\u2010automated Sanger sequencing. Haplotypes were constructed using Arlequin v.10.04, and linkage disequilibrium analysis was performed with Cube X.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The enzymatic activity of ASA was determined to be 1.74\u20132.09\u00a0nmol\/mg protein\/min and later correlated with genotypes and haplotypes. For the (p.Asn352Ser) variant, we found 126 (0.63) individuals with the AA genotype, 62 with AG (0.31) and 12 with GG (0.06); the frequency of the polymorphic allele was 0.215 (86 alleles, 21.5%), and the variant was in HWE (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.2484). The variant c.*96A&gt;G was also in HWE (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.2105): 185 individuals (0.925) with the AA genotype, 14 (0.07) with AG, and 1 (0.005) with (GG), with a frequency of 0.04 (4%) for the polymorphic allele. The inference of haplotypes resulted in 312 (0.78) AA, 72 (0.18) GA, and 16 (0.04) GG haplotypes. The AG haplotype was not found. The variants were found to be in linkage disequilibrium (D'\u00a0=\u00a01). Of the nine possible diplotypes, AA\/AG, AA\/GG, and AG\/GG were not found, in concordance with the hypothesis that the G allele of c.*96A&gt;G does not occur in the absence of the G allele of c.1055A&gt;G. We found a slight correlation between ASA biochemical activity and variants, mainly due to the G allele of c.*96A&gt;G in either genotypes or haplotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In Northwestern Mexico, the presence of PD\u2010ASA alleles was biochemically and molecularly determined, and the frequencies were found to be in HWE. The frequency of PD\u2010ASA for the North Western Mexican mestizo is 8%.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1305","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T04:09:11Z","timestamp":1589947751000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Arylsulfatase A pseudodeficiency in Mexico: Enzymatic activity and haplotype analysis"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7409-5418","authenticated-orcid":false,"given":"Jes\u00fas A.","family":"Ju\u00e1rez\u2010Osuna","sequence":"first","affiliation":[{"name":"Doctorado en Gen\u00e9tica Humana Centro Universitario Ciencias de la Salud Universidad de Guadalajara Guadalajara M\u00e9xico"},{"name":"Laboratorio de Diagn\u00f3stico Bioqu\u00edmico de Enfermedades Lisosomales Divisi\u00f3n de Gen\u00e9tica Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO) Instituto Mexicano del Seguro Social (IMSS) Guadalajara M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra C.","family":"Mendoza\u2010Ruvalcaba","sequence":"additional","affiliation":[{"name":"Laboratorio de Diagn\u00f3stico Bioqu\u00edmico de Enfermedades Lisosomales Divisi\u00f3n de Gen\u00e9tica Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO) Instituto Mexicano del Seguro Social (IMSS) Guadalajara M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Porras\u2010Dorantes","sequence":"additional","affiliation":[{"name":"Doctorado en Gen\u00e9tica Humana Centro Universitario Ciencias de la Salud Universidad de Guadalajara Guadalajara M\u00e9xico"},{"name":"Laboratorio de Diagn\u00f3stico Bioqu\u00edmico de Enfermedades Lisosomales Divisi\u00f3n de Gen\u00e9tica Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO) Instituto Mexicano del Seguro Social (IMSS) Guadalajara M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thiago D.","family":"Da Silva\u2010Jos\u00e9","sequence":"additional","affiliation":[{"name":"Doctorado en Gen\u00e9tica Humana Centro Universitario Ciencias de la Salud Universidad de Guadalajara Guadalajara M\u00e9xico"},{"name":"Laboratorio de Diagn\u00f3stico Bioqu\u00edmico de Enfermedades Lisosomales Divisi\u00f3n de Gen\u00e9tica Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO) Instituto Mexicano del Seguro Social (IMSS) Guadalajara M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1504-1457","authenticated-orcid":false,"given":"Jos\u00e9 E.","family":"Garc\u00eda\u2010Ortiz","sequence":"additional","affiliation":[{"name":"Laboratorio de Diagn\u00f3stico Bioqu\u00edmico de Enfermedades Lisosomales Divisi\u00f3n de Gen\u00e9tica Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente (CIBO) Instituto Mexicano del Seguro Social (IMSS) Guadalajara M\u00e9xico"},{"name":"Direcci\u00f3n de Educaci\u00f3n e Investigaci\u00f3n en Salud UMAE Hospital Gineco\u2010obstetricia CMNO\u2010IMSS Guadalajara M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,5,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.31.9.667"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-015-2417-5"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22919"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1993.tb03908.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-70909-3_19"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.23.9436"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19970905)71:4<475:AID-AJMG20<3.0.CO;2-C"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/16.3.1215"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X1999000800002"},{"issue":"3","key":"e_1_2_10_12_1","first-page":"557","article-title":"Compound heterozygosity for metachromatic leukodystrophy and arylsulfatase A pseudodeficiency alleles is not associated with progressive neurological disease","volume":"52","author":"Penzien J. 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