Variable expressivity and co‐occurrence of LDLR and LDLRAP1 mutations in familial hypercholesterolemia: failure of the dominant and recessive dichotomy
View/ Open
Author
Khalaf, Ruby
Salloum, Rony
Andary, Rabih R.
Safa, Raya
El‐Rassy, Inaam
Moubarak, Elie
Azar, Sami T.
Bitar, Fadi F.
Nemer, Georges
Published Version
https://doi.org/10.1002/mgg3.203Metadata
Show full item recordCitation
Fahed, Akl C., Ruby Khalaf, Rony Salloum, Rabih R. Andary, Raya Safa, Inaam El‐Rassy, Elie Moubarak, Sami T. Azar, Fadi F. Bitar, and Georges Nemer. 2016. “Variable expressivity and co‐occurrence of LDLR and LDLRAP1 mutations in familial hypercholesterolemia: failure of the dominant and recessive dichotomy.” Molecular Genetics & Genomic Medicine 4 (3): 283-291. doi:10.1002/mgg3.203. http://dx.doi.org/10.1002/mgg3.203.Abstract
Abstract Background: The familial inherited genetic disorder of lipoprotein metabolism affects more than 10 million individuals around the world. Lebanon is one of the several endemic areas for familial hypercholesterolemia (FH) with a founder mutation in the low‐density lipoprotein cholesterol receptor (LDLR) gene, responsible for most of the cases. We have previously shown that 16% of all familial cases with hypercholesterolemia do not show genotype segregation of LDLR with the underlying phenotype. Methods: We used Sanger sequencing to genotype 25 Lebanese families with severe FH for the gene encoding the LDLR‐associated protein (LDLRAP1), responsible for the recessive form of the disease starting with the four families that did not show any genotype‐phenotype correlation in our previous screening. Results: We showed that the previously reported p.Q136* variant is linked to the hypercholesterolemia phenotype in the four families. In addition, we showed a variable phenotype between families and between members of the same family. One family exhibits mutations in both LDLR and LDLRAP1 with family members showing differential phenotypes unexplained by the underlying genotypes of the two genes. Conclusion: The p.Q136* variant in LDLRAP1 is yet another founder mutation in Lebanon and coupled with the LDLR p.C681* variant explains all the genetic causes of FH in Lebanon.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867562/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:27320455
Collections
- HMS Scholarly Articles [17917]
- SPH Scholarly Articles [6362]
Contact administrator regarding this item (to report mistakes or request changes)