{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T17:27:43Z","timestamp":1772213263358,"version":"3.50.1"},"reference-count":29,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T00:00:00Z","timestamp":1649462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health (NIH)-National Institute of Deafness and other Disorders","award":["R01 DC011651 and R01 DC003594 (to S.M.L)."],"award-info":[{"award-number":["R01 DC011651 and R01 DC003594 (to S.M.L)."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Atypical Gaucher disease is caused by variants in the PSAP gene. Saposin C is one of four homologous proteins derived from sequential cleavage of the saposin precursor protein, prosaposin. It is an essential activator for glucocerebrosidase, which is deficient in Gaucher disease. Although atypical Gaucher disease due to deficiency of saposin C is rare, it exhibits vast phenotypic heterogeneity. Here, we report on a Pakistani family that exhibits features of Gaucher disease, i.e., prelingual profound sensorineural hearing impairment, vestibular dysfunction, hepatosplenomegaly, kyphosis, and thrombocytopenia. The family was investigated using exome and Sanger sequencing. A homozygous missense variant c.1076A&gt;C: p.(Glu359Ala) in exon 10 of the PSAP gene was observed in all affected family members. In conclusion, we identified a new likely pathogenic missense variant in PSAP in a large consanguineous Pakistani family with atypical Gaucher disease. Gaucher disease due to a deficiency of saposin C has not been previously reported within the Pakistani population. Genetic screening of patients with the aforementioned phenotypes could ensure adequate follow-up and the prevention of further complications. Our finding expands the genetic and phenotypic spectrum of atypical Gaucher disease due to a saposin C deficiency.<\/jats:p>","DOI":"10.3390\/genes13040662","type":"journal-article","created":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T05:13:08Z","timestamp":1649481188000},"page":"662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Phenotype Expansion for Atypical Gaucher Disease Due to Homozygous Missense PSAP Variant in a Large Consanguineous Pakistani Family"],"prefix":"10.3390","volume":"13","author":[{"given":"Khurram","family":"Liaqat","sequence":"first","affiliation":[{"name":"Center for Statistical Genetics, Gertrude H. Sergievsky Center, The Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA"},{"name":"Department of Biotechnology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shabir","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anushree","family":"Acharya","sequence":"additional","affiliation":[{"name":"Center for Statistical Genetics, Gertrude H. Sergievsky Center, The Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2339-3500","authenticated-orcid":false,"given":"Abdul","family":"Nasir","sequence":"additional","affiliation":[{"name":"Synthetic Protein Engineering Lab (SPEL), Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thashi","family":"Bharadwaj","sequence":"additional","affiliation":[{"name":"Center for Statistical Genetics, Gertrude H. Sergievsky Center, The Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Ansar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4294-6825","authenticated-orcid":false,"given":"Sulman","family":"Basit","sequence":"additional","affiliation":[{"name":"Center for Genetics and Inherited Diseases, Taibah University, Almadinah Almunawarah, Medina 42318, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7310-6082","authenticated-orcid":false,"given":"Isabelle","family":"Schrauwen","sequence":"additional","affiliation":[{"name":"Center for Statistical Genetics, Gertrude H. Sergievsky Center, The Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wasim","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne M.","family":"Leal","sequence":"additional","affiliation":[{"name":"Center for Statistical Genetics, Gertrude H. Sergievsky Center, The Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA"},{"name":"Taub Institute for Alzheimer\u2019s Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.ymgme.2009.05.001","article-title":"Clinical and genetic study of Japanese patients with type 3 Gaucher disease","volume":"97","author":"Tajima","year":"2009","journal-title":"Mol. Genet. 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