{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T15:43:47Z","timestamp":1783439027518,"version":"3.54.6"},"reference-count":17,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T00:00:00Z","timestamp":1682380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT104033AIA"],"award-info":[{"award-number":["WT104033AIA"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT093205 MA"],"award-info":[{"award-number":["WT093205 MA"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Warburg Micro (WARBM) syndrome is a rare heterogeneous recessive genetic disorder characterized by ocular, neurological, and endocrine problems. To date, disease\u2010causing variants in four genes have been identified to cause this syndrome; of these, <jats:italic>RAB3GAP1<\/jats:italic> variants are the most frequent. Very little is known about WARBM syndrome in rural populations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>This study aims to investigate the genetics underpinnings of WARBM syndrome in a Pashtun family with two patients from Pakistan. The patients presented with spastic diplegia, severe intellectual disability, microphthalmia, microcornea, congenital cataracts, optic atrophy, and hypogonadism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Magnetic resonance imaging (MRI) analysis revealed pronounced cerebral atrophy including corpus callosum hypoplasia and polymicrogyria. Exome sequencing and subsequent filtering identified a novel homozygous missense variant NM_001172435: c.2891A&gt;G, p.Gln964Arg in the <jats:italic>RAB3GAP1<\/jats:italic> gene. The variant was validated, and its segregation confirmed, by Sanger sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Multiple prediction tools assess this variant to be damaging, and structural analysis of the protein shows that the mutant amino acid residue affects polar contact with the neighboring atoms. It is extremely rare and is absent in all the public databases. Taken together, these observations suggest that this variant underlies Micro syndrome in our family and is extremely important for management and family planning.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Identification of this extremely rare variant extends the mutations spectrum of Micro syndrome. Screening more families, especially in underrepresented populations, will help unveil the mutation spectrum underlying this syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jdn.10264","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T06:15:43Z","timestamp":1682489743000},"page":"368-373","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exome sequencing identifies a novel pathogenic variant in <i>RAB3GAP1<\/i> causing Warburg Micro syndrome in a Pakistani family"],"prefix":"10.1002","volume":"83","author":[{"given":"Wahid","family":"Ullah","sequence":"first","affiliation":[{"name":"Centre for Omic Sciences Islamia College University  Peshawar Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Ilyas","sequence":"additional","affiliation":[{"name":"Centre for Omic Sciences Islamia College University  Peshawar Pakistan"},{"name":"Department 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