{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:05:57Z","timestamp":1772168757059,"version":"3.50.1"},"reference-count":28,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2017,12,21]],"date-time":"2017-12-21T00:00:00Z","timestamp":1513814400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007334","name":"Ministry of Health and Family Welfare, Government of India","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007334","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>Microcephaly is a genetically heterogeneous disorder and is one of the frequently notable conditions in paediatric neuropathology which exists either as a single entity or in association with other co-morbidities. More than a single gene is implicated in true microcephaly and the list is growing with the recent advancements in sequencing technologies. Using massive parallel sequencing, we identified a novel frame shift insertion in the abnormal spindle-like microcephaly-associated protein gene in a client with true autosomal recessive primary microcephaly. \u00a0Exome sequencing in the present case helped in identifying the true cause behind the disease, which helps in the premarital counselling for the sibling to avoid future recurrence of the disorder in the family.<\/ns4:p>","DOI":"10.12688\/f1000research.12102.1","type":"journal-article","created":{"date-parts":[[2017,12,21]],"date-time":"2017-12-21T10:30:17Z","timestamp":1513852217000},"page":"2163","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Whole exome sequencing identifies a novel homozygous frameshift mutation in the ASPM gene, which causes microcephaly 5, primary, autosomal recessive"],"prefix":"10.12688","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0895-7320","authenticated-orcid":false,"given":"Desaraju Suresh","family":"Bhargav","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Sreedevi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Swapna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soumya","family":"Vivek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1693-5620","authenticated-orcid":false,"given":"Srinivas","family":"Kovvali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2017,12,21]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s12920-016-0167-8","article-title":"Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly.","volume":"9","author":"P Rump","year":"2016","journal-title":"BMC Med Genomics."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"2133-40","DOI":"10.1002\/ajmg.a.37724","article-title":"Molecular and Phenotypic Spectrum of ASPM-Related Primary Microcephaly: Identification of Eight Novel Mutations.","volume":"170","author":"M Abdel-Hamid","year":"2016","journal-title":"Am J Med Genet Part A."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"391-396","DOI":"10.5144\/0256-4947.2016.391","article-title":"A novel splice-site mutation in the ASPM gene underlies autosomal recessive primary microcephaly.","volume":"36","author":"J Hashmi","year":"2016","journal-title":"Ann Saudi Med."},{"key":"ref-4","article-title":"DST Manual +Know your child\u2019s intelligence and how to improve it","author":"J Bharath Raj","year":"1983"},{"key":"ref-5","article-title":"Receptive-Expressive Emergent Language (REEL) scale.","author":"K Bzoch","year":"1971"},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"1909\u20131914","DOI":"10.1101\/gad.16830211","article-title":"ASPM regulates Wnt signaling pathway activity in the developing brain.","volume":"25","author":"J Buchman","year":"2011","journal-title":"Genes Dev."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"E126","DOI":"10.1371\/journal.pbio.0020126","article-title":"Accelerated Evolution of the ASPM Gene Controlling Brain Size Begins Prior to Human Brain Expansion.","volume":"2","author":"N Kouprina","year":"2004","journal-title":"PLoS Biol."},{"key":"ref-8","doi-asserted-by":"crossref","first-page":"2063-2070","DOI":"10.1093\/genetics\/165.4.2063","article-title":"Evolution of the Human ASPM Gene, a Major Determinant of Brain Size.","volume":"165","author":"J Zhang","year":"2003","journal-title":"Genetics."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"136-142","DOI":"10.1086\/341283","article-title":"Identification of microcephalin, a protein implicated in determining the size of the human brain.","volume":"71","author":"A Jackson","year":"2002","journal-title":"Am J Hum Genet."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"815-820","DOI":"10.1038\/sj.ejhg.5200385","article-title":"The second locus for autosomal recessive primary microcephaly (MCPH2) maps to chromosome 19q13.1-13.2.","volume":"7","author":"E Roberts","year":"1999","journal-title":"Europ J Hum Genet."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"724-727","DOI":"10.1086\/302777","article-title":"A third novel locus for primary autosomal recessive microcephaly maps to chromosome 9q34.","volume":"66","author":"L Moynihan","year":"2000","journal-title":"Am J Hum Genet."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"1465-1469","DOI":"10.1086\/302640","article-title":"Primary autosomal recessive microcephaly: homozygosity mapping of MCPH4 to chromosome 15.","volume":"65","author":"C Jamieson","year":"1999","journal-title":"Am J Hum Genet."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"1578-1580","DOI":"10.1086\/316910","article-title":"A fifth locus for primary autosomal recessive microcephaly maps to chromosome 1q31.","volume":"67","author":"L Pattison","year":"2000","journal-title":"Am J Hum Genet."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"540-542","DOI":"10.1136\/jmg.40.7.540","article-title":"A novel locus for autosomal recessive primary microcephaly (MCPH6) maps to 13q12.2.","volume":"40","author":"G Leal","year":"2003","journal-title":"J Med Genet."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"286-290","DOI":"10.1016\/j.ajhg.2009.01.017","article-title":"Mutations in STIL, encoding a pericentriolar and centrosomal protein, cause primary microcephaly.","volume":"84","author":"A Kumar","year":"2009","journal-title":"Am J Hum Genet."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"871-878","DOI":"10.1016\/j.ajhg.2012.03.016","article-title":"A truncating mutation of CEP135 causes primary microcephaly and disturbed centrosomal function.","volume":"90","author":"M Hussain","year":"2012","journal-title":"Am J Hum Genet."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"1465-1469","DOI":"10.1086\/302640","article-title":"Primary autosomal recessive microcephaly: homozygosity mapping of MCPH4 to chromosome 15.","volume":"65","author":"C Jamieson","year":"1999","journal-title":"Am J Hum Genet."},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"1097-1112","DOI":"10.1016\/j.cell.2012.10.043","article-title":"Microcephaly gene links trithorax and REST\/NRSF to control neural stem cell proliferation and differentiation.","volume":"151","author":"Y Yang","year":"2012","journal-title":"Cell."},{"key":"ref-19","doi-asserted-by":"publisher","first-page":"2200-2213","DOI":"10.1093\/hmg\/ddt072","article-title":"Mutation in PHC1 implicates chromatin remodeling in primary microcephaly pathogenesis.","volume":"22","author":"S Awad","year":"2013","journal-title":"Hum Mol Genet."},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"5199-5214","DOI":"10.1093\/hmg\/ddt374","article-title":"CDK6 associates with the centrosome during mitosis and is mutated in a large Pakistani family with primary microcephaly.","volume":"22","author":"M Hussain","year":"2013","journal-title":"Hum Molec Genet."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"1023-1039","DOI":"10.1007\/s00439-014-1443-3","article-title":"Mutations in CENPE define a novel kinetochore-centromeric mechanism for microcephalic primordial dwarfism.","volume":"133","author":"G Mirzaa","year":"2014","journal-title":"Hum Genet."},{"key":"ref-22","doi-asserted-by":"publisher","first-page":"5940-5949","DOI":"10.1093\/hmg\/ddu318","article-title":"A missense mutation in the PISA domain of HsSAS-6 causes autosomal recessive primary microcephaly in a large consanguineous Pakistani family.","volume":"23","author":"M Khan","year":"2014","journal-title":"Hum Molec Genet."},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"814-817","DOI":"10.1038\/ng.3313","article-title":"A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome.","volume":"47","author":"V Alakbarzade","year":"2015","journal-title":"Nat Genet."},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"809-813","DOI":"10.1038\/ng.3311","article-title":"Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome.","volume":"47","author":"A Guemez-Gamboa","year":"2015","journal-title":"Nat Genet."},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"200-214","DOI":"10.1016\/j.cell.2014.09.002","article-title":"A drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases.","volume":"159","author":"S Yamamoto","year":"2014","journal-title":"Cell."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"1199-1207","DOI":"10.1007\/s00439-016-1724-0","article-title":"CIT, a gene involved in neurogenic cytokinesis, is mutated in human primary microcephaly.","volume":"135","author":"S Basit","year":"2016","journal-title":"Hum Genet."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"547986","DOI":"10.1155\/2014\/547986","article-title":"Molecular and cellular basis of autosomal recessive primary microcephaly.","volume":"2014","author":"M Barbelanne","year":"2014","journal-title":"Biomed Res Int."},{"key":"ref-28","doi-asserted-by":"publisher","first-page":"249-253","DOI":"10.1136\/jmg.2008.062380","article-title":"The molecular landscape of ASPM mutations in primary microcephaly.","volume":"46","author":"A Nicholas","year":"2009","journal-title":"J Med Genet."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/6-2163\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/6-2163\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/6-2163\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T12:19:02Z","timestamp":1698841142000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/6-2163\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,21]]},"references-count":28,"URL":"https:\/\/doi.org\/10.12688\/f1000research.12102.1","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.13096.r29314","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.13096.r29354","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.13096.r29314","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.13096.r29354","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,21]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/6-2163\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.13096.r29354, Shahid Mahmood Baig, National Institute for Biotechnology and Genetic Engineering, Pakistan Institute of Engineering & Applied Sciences, Faisalabad, 12 Jan 2018, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/6-2163\/v1#referee-response-29354","order":0,"name":"referee-response-29354","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.13096.r29314, Sulman Basit, Center for Genetics and Inherited Diseases, Taibah University, Almadinah Almunawwarah, 15 Jan 2018, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/6-2163\/v1#referee-response-29314","order":1,"name":"referee-response-29314","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Grants to carry out the present project were provided by All India Institute of Speech and Hearing, an autonomous Institute under Ministry of Health and Family Welfare, Government of India, India","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}