{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T08:58:31Z","timestamp":1770627511208,"version":"3.49.0"},"reference-count":36,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T00:00:00Z","timestamp":1618963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"king abdullah international medical research center","award":["RC15\/140"],"award-info":[{"award-number":["RC15\/140"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Congenital heart defects (CHDs) are the most common types of birth defects, and global incidence of CHDs is on the rise. Despite the prevalence of CHDs, the genetic determinants of the defects are still in the process of being identified. Herein, we report a consanguineous Saudi family with three CHD affected daughters. We used whole exome sequencing (WES) to investigate the genetic cause of CHDs in the affected daughters. We found that all affected individuals were homozygous for a novel splice-altering variant (NM_001330069.1: c.265-1G&gt;T) of PRKD1, which encodes a calcium\/calmodulin-dependent protein kinase in the heart. The homozygous variant was found in the affected patients with Pulmonary Stenosis (PS), Truncus Arteriosis (TA), and Atrial Septal Defect (ASD). Based on the family\u2019s pedigree, the variant acts in an autosomal recessive manner, which makes it the second autosomal recessive variant of PRKD1 to be identified with a link to CHDs, while all other previously described variants act dominantly. Interestingly, the father of the affected daughters was also homozygous for the variant, though he was asymptomatic of CHDs himself. Since both of his sisters had CHDs as well, this raises the possibility that the novel PRKD1 variant may undergo autosomal recessive inheritance mode with gender limitation. This finding confirms that CHD can be associated with both dominant and recessive mutations of the PRKD1 gene, and it provides a new insight to genotype\u2013phenotype association between PRKD1 and CHDs. To our knowledge, this is the first report of this specific PRKD1 mutation associated with CHDs.<\/jats:p>","DOI":"10.3390\/genes12050612","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T12:47:07Z","timestamp":1619009227000},"page":"612","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Novel Autosomal Recessive Splice-Altering Variant in PRKD1 Is Associated with Congenital Heart Disease"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9193-0008","authenticated-orcid":false,"given":"Salam","family":"Massadeh","sequence":"first","affiliation":[{"name":"Developmental Medicine Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard- Health Affairs (MNG-HA), Riyadh 11481, Saudi Arabia"},{"name":"KACST-BWH Centre of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh 11442, Saudi Arabia"},{"name":"Saudi Human Genome Project (SHGP), King Abdulaziz City for Science and Technology (KACST), Satellite Lab at King Abdulaziz Medical City (KAMC), Ministry of National Guard Health Affairs (MNG-HA), Riyadh 11481, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maha","family":"Albeladi","sequence":"additional","affiliation":[{"name":"Developmental Medicine Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard- Health Affairs (MNG-HA), Riyadh 11481, Saudi Arabia"},{"name":"KACST-BWH Centre of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh 11442, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5399-5078","authenticated-orcid":false,"given":"Nour","family":"Albesher","sequence":"additional","affiliation":[{"name":"Developmental Medicine Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard- Health Affairs (MNG-HA), Riyadh 11481, Saudi Arabia"},{"name":"KACST-BWH Centre of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh 11442, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1801-5828","authenticated-orcid":false,"given":"Fahad","family":"Alhabshan","sequence":"additional","affiliation":[{"name":"Department of Cardiac Sciences, Ministry of the National Guard\u2014Health Affairs, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kapil Dev","family":"Kampe","sequence":"additional","affiliation":[{"name":"Centogene GmbH, 18055 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farah","family":"Chaikhouni","sequence":"additional","affiliation":[{"name":"Department of Cardiac Sciences, Ministry of the National Guard\u2014Health Affairs, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed S.","family":"Kabbani","sequence":"additional","affiliation":[{"name":"Department of Cardiac Sciences, Ministry of the National Guard\u2014Health Affairs, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7061-2895","authenticated-orcid":false,"given":"Christian","family":"Beetz","sequence":"additional","affiliation":[{"name":"Centogene GmbH, 18055 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manal","family":"Alaamery","sequence":"additional","affiliation":[{"name":"Developmental Medicine Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard- Health Affairs (MNG-HA), Riyadh 11481, Saudi Arabia"},{"name":"KACST-BWH Centre of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh 11442, Saudi Arabia"},{"name":"Saudi Human Genome Project (SHGP), King Abdulaziz City for Science and Technology (KACST), Satellite Lab at King Abdulaziz Medical City (KAMC), Ministry of National Guard Health Affairs (MNG-HA), Riyadh 11481, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,21]]},"reference":[{"key":"ref_1","unstructured":"Mendis, S., Puska, P., Norrving, B., Organization, W.H., Federation, W.H., and Organization, W.S. 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