{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T11:19:54Z","timestamp":1743160794290},"reference-count":16,"publisher":"Walter de Gruyter GmbH","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,28]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Pompe disease (PD) is an autosomal recessive metabolic myopathy with an average incidence of one in 40,000 live births. It has a variable age of onset and can be diagnosed within the first 3 months. Heart involvement and muscle weakness are its primary manifestations.<\/jats:p><\/jats:sec>Case presentation<\/jats:title>We describe two families affected by PD with two rare, novel variants. To date, pathogenic variants in acid \u03b1-glucosidase (GAA<\/jats:italic>) alone have accounted for all cases of the disease. Both families were screened for pathogenic sequence variations. This study presents the implications of regulatory or modifier sequences in the disease pathogenesis for the first time. A homozygous missense p.Arg854Gln variant in family A and a single heterozygous variant (p.Asn925His) in family B were found to be segregating according to the disease phenotype. The variants were not detected in our in-house database comprising 50 whole-exome sequences of healthy individuals from a local unrelated Pakistani population. In silico<\/jats:italic> analyses predicted that the variants would have deleterious effects on the protein structure.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>The variants likely underlie the infantile-onset PD (IOPD) in these Pakistani families. The study expands the mutation spectrum of GAA<\/jats:italic> associated with IOPD and highlights the insufficiency of screening the GAA<\/jats:italic> coding sequence to determine the cause of IOPD. The work should be helpful in carrier identification, improving genetic counselling, and prenatal diagnosis.<\/jats:p><\/jats:sec>","DOI":"10.1515\/jpem-2019-0477","type":"journal-article","created":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T09:03:16Z","timestamp":1581498196000},"page":"553-556","source":"Crossref","is-referenced-by-count":3,"title":["Identification of two novel variants in GAA underlying infantile-onset Pompe disease in two Pakistani families"],"prefix":"10.1515","volume":"33","author":[{"given":"Aman","family":"Ullah","sequence":"first","affiliation":[{"name":"Medical Genetics Research Laboratory, Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bibi","family":"Zubaida","sequence":"additional","affiliation":[{"name":"Medical Genetics Research Laboratory, Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huma Arshad","family":"Cheema","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology, The Children\u2019s Hospital and The Institute of Child Health, Lahore, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Naeem","sequence":"additional","affiliation":[{"name":"Medical Genetics Research Laboratory, Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","reference":[{"key":"ref11","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1186\/s12883-017-0983-2","article-title":"The humanistic burden of Pompe disease: are there still unmet needs? A systematic review","volume":"17","year":"2017","journal-title":"BMC Neurol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"e9186","DOI":"10.1097\/MD.0000000000009186","article-title":"Infantile-onset Pompe disease with neonatal debut: a case report and literature review","volume":"96","year":"2017","journal-title":"Medicine (Baltimore)"},{"key":"ref101","first-page":"3","article-title":"A molecular analysis of the GAA gene and clinical spectrum in 38 patients with Pompe disease in Japan","volume":"14","year":"2017","journal-title":"Mol Genet Metab Rep"},{"key":"ref21","first-page":"3","article-title":"A molecular analysis of the GAA gene and clinical spectrum in 38 patients with Pompe disease in Japan","volume":"14","year":"2017","journal-title":"Mol Genet Metab Rep"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/1750-1172-8-182","article-title":"Phenotypical variation within 22 families with Pompe disease","volume":"8","year":"2013","journal-title":"Orphanet J Rare Dis"},{"key":"ref41","first-page":"835","article-title":"p.D645E of acid \u03b1-glucosidase is the most common mutation in Thai patients with infantile-onset Pompe disease","volume":"14","year":"2011","journal-title":"Genet Test Mol Biomarkers"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"e9186","DOI":"10.1097\/MD.0000000000009186","article-title":"Infantile-onset Pompe disease with neonatal debut: a case report and literature review","volume":"96","year":"2017","journal-title":"Medicine (Baltimore)"},{"key":"ref61","first-page":"1","article-title":"Pompe disease: clinical perspectives. Orphan Drugs: Res","volume":"7","year":"2016","journal-title":"Rev"},{"key":"ref141","first-page":"1","article-title":"Pompe disease: clinical perspectives. Orphan Drugs: Res","volume":"7","year":"2016","journal-title":"Rev"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1186\/s12883-017-0983-2","article-title":"The humanistic burden of Pompe disease: are there still unmet needs? A systematic review","volume":"17","year":"2017","journal-title":"BMC Neurol"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ymgme.2017.10.008","article-title":"Sensitivity of whole exome sequencing in detecting infantile- and late-onset Pompe disease","volume":"122","year":"2017","journal-title":"Mol Genet Metab"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ymgme.2017.10.008","article-title":"Sensitivity of whole exome sequencing in detecting infantile- and late-onset Pompe disease","volume":"122","year":"2017","journal-title":"Mol Genet Metab"},{"key":"ref121","first-page":"835","article-title":"p.D645E of acid \u03b1-glucosidase is the most common mutation in Thai patients with infantile-onset Pompe disease","volume":"14","year":"2011","journal-title":"Genet Test Mol Biomarkers"},{"key":"ref01","first-page":"1","article-title":"Early higher dosage of alglucosidase alpha in classic Pompe disease","volume":"31","year":"2018","journal-title":"J Pediatr Endocrinol Metab"},{"key":"ref151","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/1750-1172-8-182","article-title":"Phenotypical variation within 22 families with Pompe disease","volume":"8","year":"2013","journal-title":"Orphanet J Rare Dis"},{"key":"ref81","first-page":"1","article-title":"Early higher dosage of alglucosidase alpha in classic Pompe disease","volume":"31","year":"2018","journal-title":"J Pediatr Endocrinol Metab"}],"container-title":["Journal of Pediatric Endocrinology and Metabolism"],"original-title":[],"link":[{"URL":"https:\/\/www.degruyter.com\/view\/journals\/jpem\/33\/4\/article-p553.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2019-0477\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T01:47:07Z","timestamp":1619056027000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2019-0477\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,28]]},"references-count":16,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.1515\/jpem-2019-0477","relation":{},"ISSN":["2191-0251","0334-018X"],"issn-type":[{"value":"2191-0251","type":"electronic"},{"value":"0334-018X","type":"print"}],"subject":[],"published":{"date-parts":[[2020,4,28]]}}}