{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T08:10:00Z","timestamp":1775463000186,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neurological disorders affect both the central and peripheral nervous systems, exhibiting broad genetic and clinical variability and posing a significant public health concern. These conditions range from common disorders, such as attention deficit disorder and epilepsy, to rare diseases like intellectual disability (ID) and white matter disorders. Exome sequencing (ES) has emerged as a powerful tool in diagnosing the genetic underpinnings of these disorders. ES demonstrated its feasibility as a cost\u2010effective diagnostic pathway by identifying pertinent diagnostic outcomes in 29.4% of cases and being noticeably more cost\u2010effective than conventional genetic diagnostic techniques.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>This study investigated the genetic basis of three rare neurological disorders in three unrelated Pakistani families using ES. Each family presents with a distinct syndromic form of ID, associated with bilateral frontoparietal polymicrogyria (BFPP) (Family\u20101), Li\u2013Ghorbani\u2013Weisz\u2013Hubshman syndrome (LIGOWS) (Family\u20102), or hypomyelination and congenital cataract (HCC) (Family\u20103). The functional consequences of the missense variants were investigated using bioinformatic prediction tools to confirm the pathogenicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In Family\u20101 with BFPP, ES identified a novel homozygous missense variant ((NM_001145771.3): c.1579C\u00a0&gt;\u00a0T; (NP_001139243.1): p.Pro527Ser) in\n                      <jats:italic>ADGRG1<\/jats:italic>\n                      , predicted to impact protein function. In Family\u20102 with LIGOWS, a novel homozygous missense variant ((NM_182958.4): c.649A\u00a0&gt;\u00a0C; (NP_892003.2): p.Met217Leu) was found in\n                      <jats:italic>KAT8<\/jats:italic>\n                      . In Family\u20103 with HCC, a novel homozygous nonsense variant ((NM_032581.4): c.722T\u00a0&gt;\u00a0G; (NP_115970.2): p.Leu241Ter) was identified in\n                      <jats:italic>FAM126A<\/jats:italic>\n                      , likely resulting in a truncated, nonfunctional protein. Families\u2019 structures and segregation analysis confirm disease condition segregating with autosomal recessive mode of inheritance. The functional consequences of the\n                      <jats:italic>ADGRG1<\/jats:italic>\n                      and\n                      <jats:italic>KAT8<\/jats:italic>\n                      missense variants were revealed as deleterious using bioinformatic prediction tools.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We have identified novel pathogenic variants in\n                      <jats:italic>ADGRG1<\/jats:italic>\n                      ,\n                      <jats:italic>KAT8<\/jats:italic>\n                      , and\n                      <jats:italic>FAM126A<\/jats:italic>\n                      in individuals with rare neurological disorders, thereby expanding the genetic and clinical spectrum of these conditions. This study reports, for the first time, an autosomal recessive inheritance pattern for a KAT8\u2010related disorder, providing new insights into its genetic architecture.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ahg.70030","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T09:45:49Z","timestamp":1764927949000},"page":"167-175","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Genetic Basis of Neurological Disorders: Missense and Nonsense Variants in Three Pakistani Families With Syndromic Intellectual Disability"],"prefix":"10.1111","volume":"90","author":[{"given":"Kenza","family":"Javed","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science &amp; Technology (KUST)  Kohat Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nazif","family":"Muhammad","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science &amp; Technology (KUST)  Kohat Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syeda Iqra","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science &amp; Technology (KUST)  Kohat Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fozia","family":"Fozia","sequence":"additional","affiliation":[{"name":"Biochemistry Department KMU Institute of Dental Sciences  Kohat Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Irfan","family":"Ullah","sequence":"additional","affiliation":[{"name":"Saidu Medical College  Swat Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shah","family":"Qiaz","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science &amp; Technology (KUST)  Kohat Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samin","family":"Jan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science &amp; Technology (KUST)  Kohat Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salah ud","family":"Din","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science &amp; Technology (KUST)  Kohat Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adil U.","family":"Reman","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science &amp; Technology (KUST)  Kohat Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Daud","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science &amp; Technology (KUST)  Kohat Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shamim","family":"Saleha","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science &amp; Technology (KUST)  Kohat Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noor","family":"Muhammad","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science &amp; Technology (KUST)  Kohat Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naveed","family":"Wasif","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Ulm University  Ulm Germany"},{"name":"Institut f\u00fcr Humangenetik Universit\u00e4tsklinikum Schleswig\u2010Holstein, Campus Kiel  Kiel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saadullah","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Kohat University of Science &amp; Technology (KUST)  Kohat Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3271"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21175"},{"issue":"5","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1002\/ana.10520","article-title":"Bilateral Frontoparietal Polymicrogyria: Clinical and Radiological Features in 10 Families With Linkage to Chromosome 16","volume":"53","author":"Chang B. S.","year":"2003","journal-title":"Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(21)00395-3"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073815583335"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43042-024-00499-1"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032180"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.01.008"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.3591"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(96)00147-5"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.09.003"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12685"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq078"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI131145"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.200"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e23688"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092780"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1612591"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13848"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31399"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2020.11.002"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-024-02063-4"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2012.06.004"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.1"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201800078"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42256-019-0086-4"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1870"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2021.11.106"}],"container-title":["Annals of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ahg.70030","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ahg.70030","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ahg.70030","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T07:23:37Z","timestamp":1775460217000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ahg.70030"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,5]]},"references-count":29,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1111\/ahg.70030"],"URL":"https:\/\/doi.org\/10.1111\/ahg.70030","archive":["Portico"],"relation":{},"ISSN":["0003-4800","1469-1809"],"issn-type":[{"value":"0003-4800","type":"print"},{"value":"1469-1809","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,5]]},"assertion":[{"value":"2025-08-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}