Novel Autosomal Recessive Splice-Altering Variant in <i>PRKD1</i> Is Associated with Congenital Heart Disease
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 CH...
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MDPI AG
2021-04-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/5/612 |
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| author | Salam Massadeh Maha Albeladi Nour Albesher Fahad Alhabshan Kapil Dev Kampe Farah Chaikhouni Mohamed S. Kabbani Christian Beetz Manal Alaamery |
| author_facet | Salam Massadeh Maha Albeladi Nour Albesher Fahad Alhabshan Kapil Dev Kampe Farah Chaikhouni Mohamed S. Kabbani Christian Beetz Manal Alaamery |
| author_sort | Salam Massadeh |
| collection | DOAJ |
| description | 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>T) of <i>PRKD1</i>, 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’s pedigree, the variant acts in an autosomal recessive manner, which makes it the second autosomal recessive variant of <i>PRKD1</i> 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 <i>PRKD1</i> 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 <i>PRKD1</i> gene, and it provides a new insight to genotype–phenotype association between <i>PRKD1</i> and CHDs. To our knowledge, this is the first report of this specific <i>PRKD1</i> mutation associated with CHDs. |
| first_indexed | 2024-03-10T12:07:37Z |
| format | Article |
| id | doaj.art-6aeaa6cabd9b4c3a86479567cbec8548 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T12:07:37Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-6aeaa6cabd9b4c3a86479567cbec85482023-11-21T16:26:27ZengMDPI AGGenes2073-44252021-04-0112561210.3390/genes12050612Novel Autosomal Recessive Splice-Altering Variant in <i>PRKD1</i> Is Associated with Congenital Heart DiseaseSalam Massadeh0Maha Albeladi1Nour Albesher2Fahad Alhabshan3Kapil Dev Kampe4Farah Chaikhouni5Mohamed S. Kabbani6Christian Beetz7Manal Alaamery8Developmental 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 ArabiaDevelopmental 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 ArabiaDevelopmental 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 ArabiaDepartment of Cardiac Sciences, Ministry of the National Guard—Health Affairs, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi ArabiaCentogene GmbH, 18055 Rostock, GermanyDepartment of Cardiac Sciences, Ministry of the National Guard—Health Affairs, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi ArabiaDepartment of Cardiac Sciences, Ministry of the National Guard—Health Affairs, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi ArabiaCentogene GmbH, 18055 Rostock, GermanyDevelopmental 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 ArabiaCongenital 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>T) of <i>PRKD1</i>, 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’s pedigree, the variant acts in an autosomal recessive manner, which makes it the second autosomal recessive variant of <i>PRKD1</i> 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 <i>PRKD1</i> 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 <i>PRKD1</i> gene, and it provides a new insight to genotype–phenotype association between <i>PRKD1</i> and CHDs. To our knowledge, this is the first report of this specific <i>PRKD1</i> mutation associated with CHDs.https://www.mdpi.com/2073-4425/12/5/612<i>PRKD1</i>congenital heart diseasesplice altering variantwhole exome sequencingmultiple affected |
| spellingShingle | Salam Massadeh Maha Albeladi Nour Albesher Fahad Alhabshan Kapil Dev Kampe Farah Chaikhouni Mohamed S. Kabbani Christian Beetz Manal Alaamery Novel Autosomal Recessive Splice-Altering Variant in <i>PRKD1</i> Is Associated with Congenital Heart Disease Genes <i>PRKD1</i> congenital heart disease splice altering variant whole exome sequencing multiple affected |
| title | Novel Autosomal Recessive Splice-Altering Variant in <i>PRKD1</i> Is Associated with Congenital Heart Disease |
| title_full | Novel Autosomal Recessive Splice-Altering Variant in <i>PRKD1</i> Is Associated with Congenital Heart Disease |
| title_fullStr | Novel Autosomal Recessive Splice-Altering Variant in <i>PRKD1</i> Is Associated with Congenital Heart Disease |
| title_full_unstemmed | Novel Autosomal Recessive Splice-Altering Variant in <i>PRKD1</i> Is Associated with Congenital Heart Disease |
| title_short | Novel Autosomal Recessive Splice-Altering Variant in <i>PRKD1</i> Is Associated with Congenital Heart Disease |
| title_sort | novel autosomal recessive splice altering variant in i prkd1 i is associated with congenital heart disease |
| topic | <i>PRKD1</i> congenital heart disease splice altering variant whole exome sequencing multiple affected |
| url | https://www.mdpi.com/2073-4425/12/5/612 |
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