{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:39Z","timestamp":1787028579226,"version":"build-2736575974"},"reference-count":100,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Initiative of PTGDPRI"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rare genetic diseases (RGDs) affect individuals, families, and healthcare systems worldwide. Population-scale genomic data remain largely restricted to Western cohorts with an estimated 10,000 RGDs. South Asian populations remain underrepresented in molecular, clinical, and genomic databases. This study presents the first preliminary molecular genetic characterization of RGDs in the Punjabi population of Pakistan. Data were collected from the provincial RGD registry at the Punjab Thalassemia and Other Genetic Disorders Prevention and Research Institute (PTGDPRI), Lahore. Families diagnosed using next-generation sequencing (NGS) between 2021 and 2023 were enrolled. Structured questionnaires captured clinical, demographic, and socioeconomic information, and statistical and genetic analyses were performed to assess allele frequencies, and disease distribution. The registry included 167 families with 72 distinct RGDs, with a mean burden of 0.81 \u00b1 0.24 affected children per family. Niemann\u2013Pick disease (NP), progressive familial intrahepatic cholestasis (PFIC), and mucopolysaccharidosis (MPS) were the most common diseases. Consanguinity was observed in 89% of families, 77% of which involved first-cousin marriages, and was significantly associated with RGD incidence. Most families belonged to low-income groups despite high literacy rates, underscoring inequity in healthcare. The primary and secondary variants included 131 variants, including copy number variants (CNVs) and single nucleotide variants (SNVs), annotated as pathogenic, likely pathogenic, or variants of unknown significance (VUS) across 109 genes, including 24 South Asian-enriched variants. This study provides the first genomic and epidemiological overview of RGDs in the Punjabi population. The findings reveal how genetic, socioeconomic, and cultural factors converge to amplify the RGD burden and highlight the need for affordable molecular diagnostics, inclusive genomic databases, and regional genomic surveillance initiatives in South Asia.<\/jats:p>","DOI":"10.3390\/ijms27010206","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T14:27:51Z","timestamp":1766586471000},"page":"206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Uncovering the Molecular Signatures of Rare Genetic Diseases in the Punjabi Population"],"prefix":"10.3390","volume":"27","author":[{"given":"Iqra","family":"Tabassum","sequence":"first","affiliation":[{"name":"Forensic DNA Typing Laboratory, National Center of Excellence in Molecular Biology, University of Punjab, Lahore 53700, Pakistan"},{"name":"Punjab Thalassemia and Other Genetic Disorders Prevention and Research Institute, Sir Ganga Ram Hospital, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Shafique","sequence":"additional","affiliation":[{"name":"Forensic DNA Typing Laboratory, National Center of Excellence in Molecular Biology, University of Punjab, Lahore 53700, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3728-8680","authenticated-orcid":false,"given":"Muhammad Shoaib","family":"Akhtar","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Human Anatomy, School of Medicine, University of California Davis, Davis, CA 95616, USA"},{"name":"Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa 277-8562, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Cipriani, V., Vestito, L., Magavern, E.F., Jacobsen, J.O.B., Arno, G., Behr, E.R., Benson, K.A., Bertoli, M., Bockenhauer, D., and Bowl, M.R. 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