title: Genotypic and phenotypic presentation of transthyretin-related familial amyloid polyneuropathy (TTR-FAP) in Turkey.
abstract: Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is an autosomal dominant disorder caused by mutations of the transthyretin (TTR) gene. The mutant amyloidogenic transthyretin protein causes the systemic accumulation of amyloid fibrils that result in organ dysfunction. TTR-associated FAP is a progressive and fatal disease, if left untreated, and should be considered in the differential diagnosis of any person presenting with a progressive polyneuropathy, particularly with accompanying autonomic involvement. The clinical, electrophysiological, histopathological, and genetic characteristics of 17 patients from Turkey (5 female, 13 male) from nine families with polyneuropathy and mutations in TTR were evaluated. Sequence analysis of the TTR gene revealed five mutations (Val30Met, Glu89Gln, Gly53Glu, Glu54Gly and Gly47Glu). Mean age at disease onset was 40.4 ± 13.9 years (range 21-66 years). The most commonly reported initial complaint was paresthesia in the feet (asymmetric in three patients). Three patients (2 male) with the Glu89Gln mutation presented with carpal tunnel syndrome. Two patients with the Gly53Glu mutation showed episodes of dysarthria and hemiparesis, consistent with this genotype. Seven patients died during the period of follow-up as a result of systemic involvement. Our study suggests that a cohort of patients from Turkey with TTR-FAP exhibits clinical and genetic heterogeneity.
authors.affiliation: Neurology Department, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Hacer
authors.initials: H
authors.lastname: Durmuş-Tekçe
authors.affiliation: Neurology Department, Medical Faculty, Istanbul Bilim University, Istanbul, Turkey.
authors.forename: Zeliha
authors.initials: Z
authors.lastname: Matur
authors.affiliation: Neurology Department, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Mert Atmaca
authors.affiliation: Genetics Department, Institute of Experimental Medical Research, Istanbul University, Istanbul, Turkey.
authors.forename: Mehves
authors.initials: M
authors.lastname: Poda
authors.affiliation: Neurology Department, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Arman
authors.initials: A
authors.lastname: Çakar
authors.affiliation: Neurology Department, Gulhane Military Medical Academy, Ankara, Turkey.
authors.forename: Ümit
authors.initials: Ü
authors.lastname: Hıdır Ulaş
authors.affiliation: Neurology Department, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Piraye
authors.initials: P
authors.lastname: Oflazer-Serdaroğlu
authors.affiliation: Neurology Department, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Feza
authors.initials: F
authors.lastname: Deymeer
authors.affiliation: Neurology Department, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey. Electronic address: parmany@istanbul.edu.tr.
authors.forename: Yesim G
authors.initials: YG
authors.lastname: Parman
mesh_terms: D000328:Adult; D000368:Aged; D028227:Amyloid Neuropathies, Familial / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology*; D004576:Electromyography; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009431:Neural Conduction; D011228:Prealbumin / Q000235:genetics*; D014421:Turkey; D055815:Young Adult
chemical_list: D011228:Prealbumin
keywords: Hereditary; Heterogeneity; Neuropathy; Progressive; Transthyretin-related familial amyloid polyneuropathy