{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:57:35Z","timestamp":1753869455090,"version":"3.41.2"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T00:00:00Z","timestamp":1737417600000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Homocystinuria due to cystathionine beta\u2010synthase (CBS) deficiency is a rare metabolic disorder inherited as an autosomal recessive trait. Spectrum of genetic variants in <jats:italic>CBS<\/jats:italic> gene and their correlation with the phenotypes of homocystinuria in Sri Lankan patients have not been reported to date. The objective of this study was to identify the genotypes and genotype\u2013phenotype correlations in a cohort of Sri Lankan patients with homocystinuria due to CBS deficiency. We determined the variants in <jats:italic>CBS<\/jats:italic> gene in 14 Sri Lankan patients with homocystinuria, from 9 unrelated families. The clinical features and the biochemical response to pyridoxine were studied for further correlations. Among the 14 patients, the common clinical features were ectopia lentis (100%), intellectual disability (92%) and marfanoid features (78%) at presentation while three of them had developed osteoporosis (21%). Median age at diagnosis was 8\u2009years (range 2\u201312). Three pathogenic variants (c.1006C&gt;T, c.785C&gt;T and c.19del) and two likely pathogenic variants (c.869C&gt;T, c.772G&gt;A) in <jats:italic>CBS<\/jats:italic> gene were identified. Thirteen patients with homozygous genotypes were non\u2010responsive to pyridoxine while the only patient with the compound heterozygous genotype (c.869C&gt;T\/c.772G&gt;A) responded to pyridoxine treatment. The genotypic spectrum observed in Sri Lankan patients is unique and mostly associated with pyridoxine non\u2010responsiveness. The majority of the patients were identified clinically at a later stage of the disease due to lack of a screening programme in the country. Therefore, it is important to improve the awareness of the disease among the clinicians in the interest of early diagnosis and early commencement of metabolic treatment.<\/jats:p>","DOI":"10.1002\/jmd2.12470","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T08:53:48Z","timestamp":1737449628000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genotypic Spectrum in a Cohort of Sri Lankan Patients With Homocystinuria"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7493-051X","authenticated-orcid":false,"given":"Hewa Warawitage","family":"Dilanthi","sequence":"first","affiliation":[{"name":"Department of Chemical Pathology Lady Ridgeway Hospital for Children  Colombo Sri Lanka"},{"name":"Department of Biochemistry and Molecular Biology, Faculty of Medicine University of Colombo  Sri Lanka"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kandana Liyanage Subhashinie","family":"Jayasena","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology Lady Ridgeway Hospital for Children  Colombo Sri Lanka"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nambage Dona Priyani","family":"Dhammika","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology Lady Ridgeway Hospital for Children  Colombo Sri Lanka"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7963-234X","authenticated-orcid":false,"given":"Neluwa Liyanage Ruwan","family":"Indika","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology Lady Ridgeway Hospital for Children  Colombo Sri Lanka"},{"name":"Department of Biochemistry, Faculty of Medical Sciences University of Sri Jayewardenepura  Nugegoda Sri Lanka"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matara Mahavidanage Nishani","family":"De Silva","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology Lady Ridgeway Hospital for Children  Colombo Sri Lanka"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imalke","family":"Kankananarachchi","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Faculty of Medicine University of Ruhuna  Galle Sri Lanka"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pushpa Malkanthi Gardiye","family":"Punchihewa","sequence":"additional","affiliation":[{"name":"Paediatric Unit Lady Ridgeway Hospital for Children  Colombo Sri Lanka"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dharma","family":"Irugalbandara","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit Lady Ridgeway Hospital for Children  Colombo Sri Lanka"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6515-6944","authenticated-orcid":false,"given":"Sabine","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Centogene GmbH  Rostock Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kosala","family":"Karunaratne","sequence":"additional","affiliation":[{"name":"Paediatric Unit Lady Ridgeway Hospital for Children  Colombo Sri Lanka"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6265-0461","authenticated-orcid":false,"given":"Eresha","family":"Jasinge","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology Lady Ridgeway Hospital for Children  Colombo Sri Lanka"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,21]]},"reference":[{"key":"e_1_2_12_2_1","first-page":"2007","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Mudd S. 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