title: Transthyretin V122I (pV142I)* cardiac amyloidosis: an age-dependent autosomal dominant cardiomyopathy too common to be overlooked as a cause of significant heart disease in elderly African Americans.
abstract: Since the identification of a valine-to-isoleucine substitution at position 122 (TTR V122I; pV142I) in the transthyretin (TTR)-derived fibrils extracted from the heart of a patient with late-onset cardiac amyloidosis, it has become clear that the amyloidogenic mutation and the disease occur almost exclusively in individuals of identifiable African descent. In the United States, the amyloidogenic allele frequency is 0.0173 and is carried by 3.5% of community-dwelling African Americans. Genotyping across Africa indicates that the origin of the allele is in the West African countries that were the major source of the slave trade to North America. At autopsy, the allele was found to be associated with cardiac TTR amyloid deposition in all the carriers after age 65 years; however, the clinical penetrance varies, resulting in substantial heart disease in some carriers and few symptoms in others. The allele has been found in 10% of African Americans older than age 65 with severe congestive heart failure. At this time there are potential forms of therapy in clinical trials. The combination of a highly accurate genetic test and the potential for specific therapy demands a greater awareness of this autosomal dominant, age-dependent cardiac disease in the cardiology community.Genet Med advance online publication 19 January 2017.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Joel N
authors.identifier: 0000-0001-5216-6414
authors.initials: JN
authors.lastname: Buxbaum
authors.affiliation: Amyloidosis Center and Section of Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts, USA.
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Ruberg
mesh_terms: D000328:Adult; D000349:Africa / Q000453:epidemiology; D001741:Black or African American / Q000235:genetics*; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000686:Amyloidosis / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D009202:Cardiomyopathies / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D005260:Female; D005787:Gene Frequency; D006333:Heart Failure / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011228:Prealbumin / Q000235:genetics* / Q000378:metabolism; D015995:Prevalence
chemical_list: D011228:Prealbumin