Lama AlAbdi1,2, Shatha Alrashseed3, Ahood Alsulaiman4, Rana Helaby2, Faiqa Imtiaz4, Mohamed Alhamed4, Fowzan S Alkuraya5. 1. Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia. 2. Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. 3. King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia. 4. Department of Clinical Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. 5. Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.
Abstract
PURPOSE: Consanguineous couples are typically counseled based on familial pathogenic variants identified in affected children. The residual risk for additional autosomal recessive (AR) variants, however, remains largely understudied. METHODS: First, we surveyed pedigrees of 1,859 consanguineous families for evidence of more than one AR disease. Second, we mined our database of 1,773 molecularly tested consanguineous families to identify those with more than one AR disease. Finally, we surveyed 88 women from consanguineous unions who have undergone targeted prenatal testing for a familial AR variant and followed the pregnancy outcome (n = 144). RESULTS: We found suggestive evidence of more than one AR disease in 1.94% of consanguineous pedigrees surveyed. Of 1,773 molecularly characterized consanguineous families, 2.93% had evidence of at least two AR diseases (3.54% for first cousin or closer and 2.72% for second cousin or more distant). Furthermore, we found that in 2.78% of pregnancies negative for the familial variant, the pregnancy outcome was a child with a different AR disease. CONCLUSION: Our results show that when counseling consanguineous couples for a familial AR variant, ~3% residual risk for additional AR variants should be discussed. This suggests that a broader testing strategy in consanguineous couples should be considered.
PURPOSE: Consanguineous couples are typically counseled based on familial pathogenic variants identified in affected children. The residual risk for additional autosomal recessive (AR) variants, however, remains largely understudied. METHODS: First, we surveyed pedigrees of 1,859 consanguineous families for evidence of more than one AR disease. Second, we mined our database of 1,773 molecularly tested consanguineous families to identify those with more than one AR disease. Finally, we surveyed 88 women from consanguineous unions who have undergone targeted prenatal testing for a familial AR variant and followed the pregnancy outcome (n = 144). RESULTS: We found suggestive evidence of more than one AR disease in 1.94% of consanguineous pedigrees surveyed. Of 1,773 molecularly characterized consanguineous families, 2.93% had evidence of at least two AR diseases (3.54% for first cousin or closer and 2.72% for second cousin or more distant). Furthermore, we found that in 2.78% of pregnancies negative for the familial variant, the pregnancy outcome was a child with a different AR disease. CONCLUSION: Our results show that when counseling consanguineous couples for a familial AR variant, ~3% residual risk for additional AR variants should be discussed. This suggests that a broader testing strategy in consanguineous couples should be considered.
Authors: Sandy Siegert; Gabriel T Mindler; Christof Brücke; Andreas Kranzl; Janina Patsch; Markus Ritter; Andreas R Janecke; Julia Vodopiutz Journal: Genes (Basel) Date: 2021-10-20 Impact factor: 4.096
Authors: Zornitza Stark; Michael Fahey; Ari Horton; Kai Mun Hong; Dinusha Pandithan; Meredith Allen; Caroline Killick; Stacy Goergen; Amanda Springer; Dean Phelan; Melanie Marty; Rebecca Halligan; Joy Lee; James Pitt; Belinda Chong; John Christodoulou; Sebastian Lunke Journal: Cold Spring Harb Mol Case Stud Date: 2022-03-24