Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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Case Reports
Cardiac amyloidosis associated with the transthyretin Ile122 mutation in a Caucasian family.
The Ile122 transthyretin variant associated with restrictive cardiomyopathy has been described in African-Americans and estimated to be present in approximately 4% of the Black population. We report the first American-Caucasian family with cardiomyopathy due to the TTR Ile122 mutation. The high prevalence of this mutation in the Black population and the discovery that it may cause disease in other ethnic populations highlights the importance of considering this autosomal dominant systemic amyloidosis in all individuals with restrictive cardiomyopathy. Inadequate diagnosis combined with inappropriate treatment may have a significant impact on morbidity and mortality.
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The standardization and clinical validation of the measurement of beta-amyloid(1-42) (Abeta42) in cerebrospinal fluid (CSF), plasma and urine is described using a commercially available sandwich-type ELISA with 21F12 and 3D6 as monoclonal antibodies. The INNOTEST beta-amyloid(1-42) allows the specific and reliable measurement of(1-42) amyloid peptides in CSF and plasma. The Abeta42 concentrations in serum and urine were below the detection limit. ⋯ No correlation was found in AD patients between CSF and plasma concentrations of Abeta42 or between CSF Abeta42 levels and blood-brain-barrier function. The quantitative outcome of the test is in part dependent on confounding factors such as tube type, freeze/thaw cycles, temperature of incubation, standard preparation protocol, and antibody selection. Notwithstanding these aspects, it emerged that Abeta42 is a useful biochemical marker for the diagnosis of AD patients, but there is a need for an international Abeta standard, a universally accepted protocol for CSF preparation, and a thorough evaluation of assay performance in function of the boundary conditions.
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The gene frequency of the transthyretin (TTR) mutation (Val122Ile) was studied in African and African-American populations. The African populations analyzed included the Zulu and Xhosa of South Africa, and Yorubas from the city of Ibadan, Nigeria. ⋯ The Val122Ile TTR mutation was identified in 1 of 55 Zulu, 0 of 34 Xhosa, 0 of 9 Nigerian subjects, 5 of 51 Veteran patients, and 3 of 103 newborns. Assuming the 2.91% prevalence in newborns to be the norm, there is a significant increased prevalence in the VA patient population.
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Case Reports
A novel variant of transthyretin (Glu89Lys) associated with familial amyloidotic polyneuropathy.
We detected a point mutation in the transthyretin (TTR) gene associated with familial amyloidotic polyneuropathy (FAP) in a 57-year old male presenting with sensorimotor polyneuropathy, severe autonomic dysfunction and cardiomyopathy using a non-isotopic RNase cleavage assay (NIRCA). NIRCA suggested that the mutation site was near either amino acid position 58 of mature TTR or the 3' end of exon 3. ⋯ The site of this mutation is near the 3' end of exon 3, consistent with the result of NIRCA. This mutation was also confirmed by polymerase chain reaction-induced mutation restriction analysis (PCR-IMRA).