{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T14:43:16Z","timestamp":1774276996000,"version":"3.50.1"},"reference-count":81,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2019,10,24]],"date-time":"2019-10-24T00:00:00Z","timestamp":1571875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010221","name":"Higher Education Commision, Pakistan","doi-asserted-by":"publisher","award":["4857\/NRPU\/R&amp;D\/HEC 2014"],"award-info":[{"award-number":["4857\/NRPU\/R&amp;D\/HEC 2014"]}],"id":[{"id":"10.13039\/501100010221","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005156","name":"Alexander von Humboldt-Stiftung","doi-asserted-by":"publisher","award":["2015"],"award-info":[{"award-number":["2015"]}],"id":[{"id":"10.13039\/100005156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The dental abnormalities are the typical features of many ectodermal dysplasias along with congenital malformations of nails, skin, hair, and sweat glands. However, several reports of non-syndromic\/isolated tooth agenesis have also been found in the literature. The characteristic features of hypohidrotic ectodermal dysplasia (HED) comprise of hypodontia\/oligodontia, along with hypohidrosis\/anhidrosis, and hypotrichosis. Pathogenic variants in EDA, EDAR, EDARADD, and TRAF6, cause the phenotypic expression of HED. Genetic alterations in EDA and WNT10A cause particularly non-syndromic\/isolated oligodontia. In the current project, we recruited 57 patients of 17 genetic pedigrees (A-Q) from different geographic regions of the world, including Pakistan, Egypt, Saudi Arabia, and Syria. The molecular investigation of different syndromic and non-syndromic dental conditions, including hypodontia, oligodontia, generalized odontodysplasia, and dental crowding was carried out by using exome and Sanger sequencing. We have identified a novel missense variant (c.311G&gt;A; p.Arg104His) in WNT10A in three oligodontia patients of family A, two novel sequence variants (c.207delinsTT, p.Gly70Trpfs*25 and c.1300T&gt;G; p.Try434Gly) in EDAR in three patients of family B and four patients of family C, respectively. To better understand the structural and functional consequences of missense variants in WNT10A and EDAR on the stability of the proteins, we have performed extensive molecular dynamic (MD) simulations. We have also identified three previously reported pathogenic variants (c.1076T&gt;C; p.Met359Thr), (c.1133C&gt;T; p.Thr378Met) and (c.594_595insC; Gly201Argfs*39) in EDA in family D (four patients), E (two patients) and F (one patient), correspondingly. Presently, our data explain the genetic cause of 18 syndromic and non-syndromic tooth agenesis patients in six autosomal recessive and X-linked pedigrees (A-F), which expand the mutational spectrum of these unique clinical manifestations.<\/jats:p>","DOI":"10.3390\/ijms20215282","type":"journal-article","created":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T04:41:27Z","timestamp":1571978487000},"page":"5282","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Deleterious Variants in WNT10A, EDAR, and EDA Causing Isolated and Syndromic Tooth Agenesis: A Structural Perspective from Molecular Dynamics Simulations"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4524-8355","authenticated-orcid":false,"given":"Asia","family":"Parveen","sequence":"first","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology (IMBB), Center for Research in Molecular Medicine (CRiMM), The University of Lahore, Lahore 54000, Pakistan"},{"name":"Faculty of Life Sciences, University of Central Punjab (UCP), Lahore 54000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sher Alam","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat 26000, Khyber Pakhtunkhwa, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9120-2414","authenticated-orcid":false,"given":"Muhammad Usman","family":"Mirza","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, REGA Institute for Medical Research, Medicinal Chemistry, University of Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hina","family":"Bashir","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology (IMBB), Center for Research in Molecular Medicine (CRiMM), The University of Lahore, Lahore 54000, Pakistan"},{"name":"Department of Biochemistry, Sharif Medical and Dental College, Lahore 54000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatima","family":"Arshad","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology (IMBB), Center for Research in Molecular Medicine (CRiMM), The University of Lahore, Lahore 54000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology (IMBB), Center for Research in Molecular Medicine (CRiMM), The University of Lahore, Lahore 54000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waseem","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology (IMBB), Center for Research in Molecular Medicine (CRiMM), The University of Lahore, Lahore 54000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahsan","family":"Wahab","sequence":"additional","affiliation":[{"name":"Baptist Medical Center, University of Alabama at Birmingham, Montgomery, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amal","family":"Fiaz","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology (IMBB), Center for Research in Molecular Medicine (CRiMM), The University of Lahore, Lahore 54000, Pakistan"},{"name":"Department of Allied Health Sciences, Superior University, Lahore 54000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sidra","family":"Naz","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology (IMBB), Center for Research in Molecular Medicine (CRiMM), The University of Lahore, Lahore 54000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fareeha","family":"Ashraf","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology (IMBB), Center for Research in Molecular Medicine (CRiMM), The University of Lahore, Lahore 54000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tayyaba","family":"Mobeen","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology (IMBB), Center for Research in Molecular Medicine (CRiMM), The University of Lahore, Lahore 54000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salman","family":"Aziz","sequence":"additional","affiliation":[{"name":"Institute of Advanced Dental Sciences and Research, Lahore 54000, Pakistan"},{"name":"Dental Section, Azra Naheed Medical College, Superior University, Lahore 54000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9173-8566","authenticated-orcid":false,"given":"Syed Shoaib","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology (IMBB), Center for Research in Molecular Medicine (CRiMM), The University of Lahore, Lahore 54000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noor","family":"Muhammad","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat 26000, Khyber Pakhtunkhwa, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8902-9018","authenticated-orcid":false,"given":"Nehal F.","family":"Hassib","sequence":"additional","affiliation":[{"name":"Orodental Genetics Department, National Research Centre, Giza 12622, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mostafa I.","family":"Mostafa","sequence":"additional","affiliation":[{"name":"Orodental Genetics Department, National Research Centre, Giza 12622, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nagwa E.","family":"Gaboon","sequence":"additional","affiliation":[{"name":"Medical Genetics Center, Faculty of Medicine, AinShams University, Cairo 12413, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5294-8421","authenticated-orcid":false,"given":"Roquyya","family":"Gul","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, Gulab Devi Educational Complex, Lahore, Ferozepur Road, Lahore 54000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saadullah","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat 26000, Khyber Pakhtunkhwa, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matheus","family":"Froeyen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, REGA Institute for Medical Research, Medicinal Chemistry, University of Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1296-5005","authenticated-orcid":false,"given":"Muhammad","family":"Shoaib","sequence":"additional","affiliation":[{"name":"Biotech Research and Innovation Center (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3455-8833","authenticated-orcid":false,"given":"Naveed","family":"Wasif","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology (IMBB), Center for Research in Molecular Medicine (CRiMM), The University of Lahore, Lahore 54000, Pakistan"},{"name":"Institute of Human Genetics, University of Ulm, 89081 Ulm, Germany"},{"name":"Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, D-24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/ajmg.1320530207","article-title":"Ectodermal dysplasias: A clinical classification and a causal review","volume":"53","author":"Pinheiro","year":"1994","journal-title":"Am. 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