{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:05:59Z","timestamp":1791407159659,"version":"4.3.3"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,2,22]],"date-time":"2017-02-22T00:00:00Z","timestamp":1487721600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100009983","name":"Center for Molecular Medicine Cologne (CMMC)","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009983","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:p>Autosomal recessive primary microcephaly (<jats:styled-content style=\"fixed-case\">MCPH<\/jats:styled-content>) is a rare and heterogeneous genetic disorder characterized by reduced head circumference, low cognitive prowess and, in general, architecturally normal brains. As many as 14 different loci have already been mapped. We recruited 35 <jats:styled-content style=\"fixed-case\">MCPH<\/jats:styled-content> families in Pakistan and could identify the genetic cause of the disease in 31 of them. Using homozygosity mapping complemented with whole\u2010exome, gene panel or Sanger sequencing, we identified 12 novel mutations in 3 known <jats:styled-content style=\"fixed-case\">MCPH<\/jats:styled-content>\u2010associated genes\u00a0\u2013\u00a09 in <jats:italic><jats:styled-content style=\"fixed-case\">ASPM<\/jats:styled-content><\/jats:italic>, 2 in <jats:italic><jats:styled-content style=\"fixed-case\">MCPH1<\/jats:styled-content><\/jats:italic> and 1 in <jats:italic><jats:styled-content style=\"fixed-case\">CDK5RAP2<\/jats:styled-content><\/jats:italic>. The 2 <jats:italic><jats:styled-content style=\"fixed-case\">MCPH1<\/jats:styled-content><\/jats:italic> mutations were homozygous microdeletions of 164,250 and 577,594\u2009bp, respectively, for which we were able to map the exact breakpoints. We also identified four known mutations \u2014 three in <jats:italic><jats:styled-content style=\"fixed-case\">ASPM<\/jats:styled-content><\/jats:italic> and one in <jats:italic><jats:styled-content style=\"fixed-case\">WDR62<\/jats:styled-content>.<\/jats:italic> The latter was initially deemed to be a missense mutation but we demonstrate here that it affects splicing. As to <jats:italic><jats:styled-content style=\"fixed-case\">ASPM<\/jats:styled-content><\/jats:italic>, as many as 17 out of 27 <jats:styled-content style=\"fixed-case\">MCPH5<\/jats:styled-content> families that we ascertained in our sample were found to carry the previously reported founder mutation p.Trp1326*. This study adds to the mutational spectra of four known <jats:styled-content style=\"fixed-case\">MCPH<\/jats:styled-content>\u2010associated genes and updates our knowledge about the genetic heterogeneity of <jats:styled-content style=\"fixed-case\">MCPH<\/jats:styled-content> in the Pakistani population considering its ethnic diversity.<\/jats:p>","DOI":"10.1111\/cge.12955","type":"journal-article","created":{"date-parts":[[2016,12,22]],"date-time":"2016-12-22T15:09:10Z","timestamp":1482419350000},"page":"62-68","source":"Crossref","is-referenced-by-count":29,"title":["Genetic heterogeneity in Pakistani microcephaly families revisited"],"prefix":"10.1111","volume":"92","author":[{"given":"I.","family":"Ahmad","sequence":"first","affiliation":[{"name":"Cologne Center for Genomics (CCG) University of Cologne  Cologne Germany"},{"name":"Institute of Biochemistry I, Medical Faculty University of Cologne  Cologne Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC) University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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R.","family":"Toliat","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics (CCG) University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"N\u00fcrnberg","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics (CCG) University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Dalibor","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics (CCG) University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Moawia","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics (CCG) University of Cologne  Cologne Germany"},{"name":"Health Biotechnology Division National Institute for Biotechnology and Genetic Engineering (NIBGE)  Faisalabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. S.","family":"Waseem","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics (CCG) University of Cologne  Cologne Germany"},{"name":"Health Biotechnology Division National Institute for Biotechnology and Genetic Engineering (NIBGE)  Faisalabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Asif","sequence":"additional","affiliation":[{"name":"Health Biotechnology Division National Institute for Biotechnology and Genetic Engineering (NIBGE)  Faisalabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Nagra","sequence":"additional","affiliation":[{"name":"Health Biotechnology Division National Institute for Biotechnology and Genetic Engineering (NIBGE)  Faisalabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Sher","sequence":"additional","affiliation":[{"name":"Health Biotechnology Division National Institute for Biotechnology and Genetic Engineering (NIBGE)  Faisalabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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