Residual risk for additional recessive diseases in consanguineous couples

• Published in: Genetics in medicine Vol. 23; no. 12; pp. 2448 - 2454
• Main Authors: AlAbdi, Lama, Alrashseed, Shatha, Alsulaiman, Ahood, Helaby, Rana, Imtiaz, Faiqa, Alhamed, Mohamed, Alkuraya, Fowzan S.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2021; Elsevier Limited
• Subjects: Biomedical and Life Sciences; Biomedicine; Brief Communication; Disease; Human Genetics; Laboratory Medicine
• ISSN: 1098-3600; 1530-0366
• DOI: 10.1038/s41436-021-01289-5

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.