{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:45:22Z","timestamp":1785415522475,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["414786233"],"award-info":[{"award-number":["414786233"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"award":["414786233"],"award-info":[{"award-number":["414786233"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Germany\u2019s Excellence Strategy","award":["390661388"],"award-info":[{"award-number":["390661388"]}]},{"DOI":"10.13039\/501100003390","name":"Fritz-Thyssen Stiftung","doi-asserted-by":"crossref","award":["10.23.1.013MN"],"award-info":[{"award-number":["10.23.1.013MN"]}],"id":[{"id":"10.13039\/501100003390","id-type":"DOI","asserted-by":"crossref"}]},{"award":["10.23.1.013MN"],"award-info":[{"award-number":["10.23.1.013MN"]}],"id":[{"id":"https:\/\/ror.org\/00f3sc705","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Mucopolysaccharidoses (MPS) are rare lysosomal storage disorders caused by deficiencies in glycosaminoglycan (GAG)-degrading enzymes, leading to progressive multisystem involvement. Methods: We evaluated two unrelated consanguineous Pakistani families, each with three individuals showing features consistent with MPS. Affected individuals in Family 1 presented with developmental regression, severe cognitive impairment, behavioral abnormalities and facial dysmorphisms. The affected individuals in Family 2 showed classical skeletal dysplasia consistent with Morquio syndrome. Whole-exome sequencing (WES), segregation analysis, and in silico protein modeling were performed to identify and characterize pathogenic gene variants. Results: Analysis of WES data revealed a homozygous missense variant in the SGSH gene [c.548G&gt;A (p.Cys183Tyr)] in the three cases of Family 1 and a homozygous splice-site variant in the GALNS gene (c.423-1G&gt;A) in the cases of Family 2. The SGSH variant, located within the sulfatase catalytic domain and classified as likely pathogenic (ACMG), is consistent with the Sanfilippo A phenotype and represents the first clinical characterization of this allele. Regarding Family 2, we identified the GALNS mutation as a recurrent pathogenic founder allele previously reported in individuals of South Asian descent. Structural modeling of SGSH p.Cys183Tyr predicted disruption of a conserved cysteine residue and altered protein stability, likely supporting its deleterious effect. Conclusions: This study expands the spectrum of MPS-associated variants in Pakistan. The findings underscore the importance of genomic diagnostics for enabling early detection, accurate classification, and genetic counseling in populations with high consanguinity.<\/jats:p>","DOI":"10.3390\/genes17040401","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T16:34:08Z","timestamp":1774974848000},"page":"401","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and Molecular Characterization of Pakistani Mucopolysaccharidosis Families with SGSH and GALNS Deficiencies"],"prefix":"10.3390","volume":"17","author":[{"given":"Farheen Nasir","family":"Awan","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Kinnaird College for Women, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3512-5343","authenticated-orcid":false,"given":"Shumaila","family":"Zulfiqar","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Kinnaird College for Women, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liza","family":"Eiman","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Kinnaird College for Women, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Asif","sequence":"additional","affiliation":[{"name":"Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50923 Cologne, Germany"},{"name":"Cologne Center for Genomics (CCG), Faculty of Medicine, University Hospital Cologne, University of Cologne, 50923 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1353-8809","authenticated-orcid":false,"given":"Muhammad Sajid","family":"Hussain","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics (CCG), Faculty of Medicine, University Hospital Cologne, University of Cologne, 50923 Cologne, Germany"},{"name":"West German Genome Center (WGGC), University of Cologne, 50923 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8122-0800","authenticated-orcid":false,"given":"Niklas","family":"Dahl","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahid Mahmood","family":"Baig","sequence":"additional","affiliation":[{"name":"Health Services Academy (HSA), Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotsugu","family":"Oda","sequence":"additional","affiliation":[{"name":"Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50923 Cologne, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine, University Hospital of Cologne, University of Cologne, 50923 Cologne, Germany"},{"name":"Institute for Systemic Inflammation Research (ISEF), University of L\u00fcbeck, 23562 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1146\/annurev-med-122313-085916","article-title":"Lysosomal storage diseases: From pathophysiology to therapy","volume":"66","author":"Parenti","year":"2015","journal-title":"Annu. 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