{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T04:48:49Z","timestamp":1777438129941,"version":"3.51.4"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["2020YFC2008200"],"award-info":[{"award-number":["2020YFC2008200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["2022A1515012102"],"award-info":[{"award-number":["2022A1515012102"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["2022E02052"],"award-info":[{"award-number":["2022E02052"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["2020YFC2008200"],"award-info":[{"award-number":["2020YFC2008200"]}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["2022A1515012102"],"award-info":[{"award-number":["2022A1515012102"]}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["2022E02052"],"award-info":[{"award-number":["2022E02052"]}]},{"name":"Xinjiang Uygur Autonomous Region Regional Collaborative Innovation Special Science and Technology Assistance Plan","award":["2020YFC2008200"],"award-info":[{"award-number":["2020YFC2008200"]}]},{"name":"Xinjiang Uygur Autonomous Region Regional Collaborative Innovation Special Science and Technology Assistance Plan","award":["2022A1515012102"],"award-info":[{"award-number":["2022A1515012102"]}]},{"name":"Xinjiang Uygur Autonomous Region Regional Collaborative Innovation Special Science and Technology Assistance Plan","award":["2022E02052"],"award-info":[{"award-number":["2022E02052"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Warburg Micro syndrome (WARBM) is an autosomal recessive neuro-ophthalmologic syndrome characterized by microcephaly, microphthalmia, congenital cataracts, cortical dysplasia, corpus callosum hypoplasia, spasticity, and hypogonadism. WARBM is divided into four subtypes according to the causative genes, of which RAB3GAP1 (OMIM# 602536) accounts for the highest proportion. We collected detailed medical records and performed whole-exome sequencing (WES) for a congenital cataract patient. A novel heterozygous frameshift RAB3GAP1 variant was detected in a boy with a rare ocular phenotype of bilateral membranous cataracts accompanied by a persistent papillary membrane. Further copy number variation (CNV) analysis identified a novel deletion on chromosome 2q21.3 that removed 4 of the 24 exons of RAB3GAP1. The patient was diagnosed with WARBM following genetic testing. The present study expands the genotypic and phenotypic spectrum of WARBM. It suggests applying whole exome sequencing (WES) and CNV analysis for the early diagnosis of syndromic diseases in children with congenital cataracts.<\/jats:p>","DOI":"10.3390\/genes13122364","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T02:20:57Z","timestamp":1671070857000},"page":"2364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Whole-Exome Sequencing and Copy Number Analysis in a Patient with Warburg Micro Syndrome"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8544-1109","authenticated-orcid":false,"given":"Qiwei","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Centre for Ocular Diseases, Sun Yat-sen University, Guangzhou 510060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingfeng","family":"Qin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Centre for Ocular Diseases, Sun Yat-sen University, Guangzhou 510060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2322-8409","authenticated-orcid":false,"given":"Xun","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Centre for Ocular Diseases, Sun Yat-sen University, Guangzhou 510060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Centre for Ocular Diseases, Sun Yat-sen University, Guangzhou 510060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoshan","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Centre for Ocular Diseases, Sun Yat-sen University, Guangzhou 510060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongni","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Centre for Ocular Diseases, Sun Yat-sen University, Guangzhou 510060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuoling","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Centre for Ocular Diseases, Sun Yat-sen University, Guangzhou 510060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3068-1276","authenticated-orcid":false,"given":"Xulin","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Centre for Ocular Diseases, Sun Yat-sen University, Guangzhou 510060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Centre for Ocular Diseases, Sun Yat-sen University, Guangzhou 510060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4672-9721","authenticated-orcid":false,"given":"Haotian","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Centre for Ocular Diseases, Sun Yat-sen University, Guangzhou 510060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3023-4057","authenticated-orcid":false,"given":"Weirong","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Centre for Ocular Diseases, Sun Yat-sen University, Guangzhou 510060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/ng1517","article-title":"Mutations of the catalytic subunit of RAB3GAP cause Warburg Micro syndrome","volume":"37","author":"Aligianis","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1111\/cge.13825","article-title":"Micro and Martsolf syndromes in 34 new patients: Refining the phenotypic spectrum and further molecular insights","volume":"98","author":"Ismail","year":"2020","journal-title":"Clin. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.ajhg.2011.03.012","article-title":"Loss-of-function mutations in RAB18 cause Warburg micro syndrome","volume":"88","author":"Bem","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.ajhg.2013.10.011","article-title":"Loss-of-function mutations in TBC1D20 cause cataracts and male infertility in blind sterile mice and Warburg micro syndrome in humans","volume":"93","author":"Liegel","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1086\/502681","article-title":"Mutation in Rab3 GTPase-activating protein (RAB3GAP) noncatalytic subunit in a kindred with Martsolf syndrome","volume":"78","author":"Aligianis","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nrm2728","article-title":"Rab GTPases as coordinators of vesicle traffic","volume":"10","author":"Stenmark","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"150047","DOI":"10.1098\/rsob.150047","article-title":"Warburg Micro syndrome is caused by RAB18 deficiency or dysregulation","volume":"5","author":"Handley","year":"2015","journal-title":"Open. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1007\/s00018-019-03050-3","article-title":"Rab18: New insights into the function of an essential protein","volume":"76","author":"Dejgaard","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1126\/science.349.6252.1064-b","article-title":"Documenting rare disease data in China","volume":"349","author":"Lin","year":"2015","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wang, Q., Zhang, X., Qin, T., Wang, D., Lin, X., Zhu, Y., Tan, H., Zhao, L., Li, J., and Lin, Z. (2022). Unusual Presentation in WAGR Syndrome: Expanding the Phenotypic and Genotypic Spectrum of the Diseases. Gene, 13.","DOI":"10.3390\/genes13081431"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2888","DOI":"10.1002\/ajmg.a.62947","article-title":"Broadening the genotypic and phenotypic spectrum of MAF in three Chinese Han congenital cataracts families","volume":"188","author":"Wang","year":"2022","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Talevich, E., Shain, A.H., Botton, T., and Bastian, B.C. (2016). CNVkit: Genome-Wide Copy Number Detection and Visualization from Targeted DNA Sequencing. PLoS Comput. Biol., 12.","DOI":"10.1371\/journal.pcbi.1004873"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13059-016-0974-4","article-title":"The Ensembl Variant Effect Predictor","volume":"17","author":"McLaren","year":"2016","journal-title":"Genome Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e12456","DOI":"10.1111\/gbb.12456","article-title":"Novel mutations and phenotypes of epilepsy-associated genes in epileptic encephalopathies","volume":"17","author":"Zhou","year":"2018","journal-title":"Genes Brain Behav."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1038\/gim.2017.210","article-title":"Modeling the ACMG\/AMP variant classification guidelines as a Bayesian classification framework","volume":"20","author":"Tavtigian","year":"2018","journal-title":"Genet. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_18","unstructured":"WHO (2006). WHO Child Growth Standards: Length\/Height-for-Age, Weight-for-Age, Weight-for-Length, Weight-for-Height and Body Mass Index-for-Age, World Health Organization (WHO)."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/s41436-019-0655-2","article-title":"Adapting ACMG\/AMP sequence variant classification guidelines for single-gene copy number variants","volume":"22","author":"Brandt","year":"2020","journal-title":"Genet. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1002\/humu.22296","article-title":"Mutation spectrum in RAB3GAP1, RAB3GAP2, and RAB18 and genotype-phenotype correlations in warburg micro syndrome and Martsolf syndrome","volume":"34","author":"Handley","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1002\/ajmg.a.61065","article-title":"Revealing the functions of novel mutations in RAB3GAP1 in Martsolf and Warburg micro syndromes","volume":"179","author":"Koparir","year":"2019","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1002\/ajmg.a.61543","article-title":"Martsolf syndrome with novel mutation in the TBC1D20 gene in a family from Iran","volume":"182","author":"Hozhabri","year":"2020","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"83","DOI":"10.4103\/1817-1745.181255","article-title":"Warburg micro syndrome in siblings from India","volume":"11","author":"Sekhon","year":"2016","journal-title":"J. Pediatr. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"214","DOI":"10.3988\/jcn.2022.18.2.214","article-title":"Novel RAB3GAP1 Mutation in the First Tunisian Family With Warburg Micro Syndrome","volume":"18","author":"Kerkeni","year":"2022","journal-title":"J. Clin. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1002\/ajmg.a.62234","article-title":"From cataract to syndrome diagnosis: Revaluation of Warburg-Micro syndrome Type 1 patients","volume":"185","author":"Elcioglu","year":"2021","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1167\/iovs.03-0635","article-title":"Incidence and cumulative risk of childhood cataract in a cohort of 2.6 million Danish children","volume":"45","author":"Haargaard","year":"2004","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_27","first-page":"2007","article-title":"Cat-Map: Putting cataract on the map","volume":"16","author":"Shiels","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1016\/j.ophtha.2014.06.006","article-title":"Personalized diagnosis and management of congenital cataract by next-generation sequencing","volume":"121","author":"Gillespie","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1001\/jamaophthalmol.2021.0385","article-title":"Genetic Analysis in a Swiss Cohort of Bilateral Congenital Cataract","volume":"139","author":"Rechsteiner","year":"2021","journal-title":"JAMA Ophthalmol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Bell, S., Malka, S., Lloyd, I.C., and Moosajee, M. (2021). Clinical Spectrum and Genetic Diagnosis of 54 Consecutive Patients Aged 0-25 with Bilateral Cataracts. Genes, 12.","DOI":"10.3390\/genes12020131"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sun, W., Xiao, X., Li, S., Guo, X., and Zhang, Q. (2014). Exome sequencing of 18 Chinese families with congenital cataracts: A new sight of the NHS gene. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100455"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kandaswamy, D.K., Prakash, M.V.S., Graw, J., Koller, S., Magyar, I., Tiwari, A., Berger, W., and Santhiya, S.T. (2020). Application of WES Towards Molecular Investigation of Congenital Cataracts: Identification of Novel Alleles and Genes in a Hospital-Based Cohort of South India. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249569"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1002\/humu.21360","article-title":"Detection of clinically relevant exonic copy-number changes by array CGH","volume":"31","author":"Boone","year":"2010","journal-title":"Hum. Mutat."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zhao, L., Liu, H., Yuan, X., Gao, K., and Duan, J. (2020). Comparative study of whole exome sequencing-based copy number variation detection tools. BMC Bioinform., 21.","DOI":"10.1186\/s12859-020-3421-1"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1101\/gr.229102","article-title":"The human genome browser at UCSC","volume":"12","author":"Kent","year":"2002","journal-title":"Genome Res."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/12\/2364\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:41:29Z","timestamp":1760146889000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/12\/2364"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,14]]},"references-count":35,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["genes13122364"],"URL":"https:\/\/doi.org\/10.3390\/genes13122364","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,14]]}}}