{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T21:12:10Z","timestamp":1788469930241,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T00:00:00Z","timestamp":1639094400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech and App Biochem"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Autosomal primary microcephaly (MCPH) is a heterogenetic disorder that affects brain's cerebral cortex size and leads to a reduction in the cranial vault. Along with the hallmark feature of reduced head circumference, microcephalic patients also exhibit a variable degree of intellectual disability as well. Genetic studies have reported 28 <jats:italic>MCPH<\/jats:italic> genes, most of which produce microtubule\u2010associated proteins and are involved in cell division. Herein this study, 14 patients from seven Pashtun origin Pakistani families of primary microcephaly were analyzed. Mutation analysis was performed through targeted Sanger DNA sequencing on the basis of phenotype\u2010linked genetic makeup. Genetic analysis in one family found a novel pathogenic DNA change in the abnormal spindle microtubule assembly (<jats:italic>ASPM<\/jats:italic>) gene (NM_018136.4:c.3871dupGA), while the rest of the families revealed recurrent nonsense mutation c.3978G&gt;A (p.Trp1326*) in the same gene. The novel reported frameshift insertion presumably truncates the protein p.(Lys1291Glyfs*14) and deletes the N\u2010terminus domains. Identification of novel ASPM\u2010truncating mutation expands the mutational spectrum of the <jats:italic>ASPM<\/jats:italic> gene, while mapping of recurrent mutation c.3978G&gt;A (p.Trp1326*) will aid in establishing its founder effect in the Khyber Pakhtunkhwa (KPK) inhabitant population of Pakistan and should be suggestively screened for premarital counseling of MCPH susceptible families. Most of the recruited families are related to first\u2010degree consanguinity. Hence, all the family elders were counseled to avoid intrafamilial marriages.<\/jats:p>","DOI":"10.1002\/bab.2286","type":"journal-article","created":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T20:45:17Z","timestamp":1637959517000},"page":"2296-2303","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Mutation screening of multiple Pakistani MCPH families revealed novel and recurrent protein\u2010truncating mutations of ASPM"],"prefix":"10.1002","volume":"69","author":[{"given":"Sadam","family":"Hussain","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science and Technology  Kohat Khyber Pakhtunkhwa Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amjad","family":"Nawaz","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science and Technology  Kohat Khyber Pakhtunkhwa Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malaika","family":"Hamid","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science and Technology  Kohat Khyber Pakhtunkhwa Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waseem","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science and Technology  Kohat Khyber Pakhtunkhwa Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iqbal Nawaz","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science and Technology  Kohat Khyber Pakhtunkhwa Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehak","family":"Afshan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science and Technology  Kohat Khyber Pakhtunkhwa Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adil","family":"Rehman","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science and Technology  Kohat Khyber Pakhtunkhwa Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid","family":"Nawaz","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science and Technology  Kohat Khyber Pakhtunkhwa Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Halswick","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Institute of Human Genetics Medical University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoaib\u2010ur","family":"Rehman","sequence":"additional","affiliation":[{"name":"Department of Biotechnology University of Science and Technology Bannu  Bannu Khyber Pakhtunkhwa Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohail","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Gomal Centre of Biochemistry and Biotechnology Gomal University  D. I. Khan Khyber Pakhtunkhwa Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9681-7765","authenticated-orcid":false,"given":"Muhammad","family":"Muzammal","sequence":"additional","affiliation":[{"name":"Gomal Centre of Biochemistry and Biotechnology Gomal University  D. I. Khan Khyber Pakhtunkhwa Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noor","family":"Muhammad","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science and Technology  Kohat Khyber Pakhtunkhwa Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abid","family":"Jan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science and Technology  Kohat Khyber Pakhtunkhwa Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saadullah","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science and Technology  Kohat Khyber Pakhtunkhwa Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Windpassinger","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Institute of Human Genetics Medical University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muzammil Ahmad","family":"Khan","sequence":"additional","affiliation":[{"name":"Gomal Centre of Biochemistry and Biotechnology Gomal University  D. 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Khan Khyber Pakhtunkhwa Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,10]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2005.04.009"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spen.2007.07.003"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2004.01.003"},{"issue":"1","key":"e_1_2_12_5_1","first-page":"51","article-title":"Genetic study of microcephaly based on Japanese material","volume":"7","author":"Komai T","year":"1955","journal-title":"Am J Hum Genet"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.1958.tb01455.x"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320270311"},{"issue":"12","key":"e_1_2_12_8_1","first-page":"1812","article-title":"Genetic study of Khyber\u2010Pukhtunkhwa resident Pakistani families presenting primary microcephaly with intellectual disability","volume":"69","author":"Ahmed J","year":"2019","journal-title":"J Pak Med Assoc"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng995"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt374"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073809346850"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1086\/379085"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.076398"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2004.00304.x"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.062380"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2013.05.001"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12041-017-0759-x"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2009.09.011"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2017.11.015"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi0113s39"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1601448"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1086\/339518"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi220"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.137.4.881"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e06-04-0371"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5408.1733"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9763"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2005.11.004"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12955"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2016.128"}],"container-title":["Biotechnology and Applied Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bab.2286","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bab.2286","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bab.2286","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T04:19:55Z","timestamp":1692591595000},"score":1,"resource":{"primary":{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/10.1002\/bab.2286"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,10]]},"references-count":29,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1002\/bab.2286"],"URL":"https:\/\/doi.org\/10.1002\/bab.2286","archive":["Portico"],"relation":{},"ISSN":["0885-4513","1470-8744"],"issn-type":[{"value":"0885-4513","type":"print"},{"value":"1470-8744","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,10]]},"assertion":[{"value":"2021-08-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}