Transthyretin Ala97Ser in Chinese–Taiwanese patients with familial amyloid polyneuropathy: Genetic studies and phenotype expression

Liu, Yo‐Tsen; Lee, Yi‐Chung; Yang, Chih‐Chao; Chen, Mai-Ling; Lin, Kon‐Ping

doi:10.1016/j.jns.2007.10.011

Cited by 27 publications

(23 citation statements)

References 28 publications

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“…Gastrointestinal (GI) symptoms (6/7, 86%), dyspnea on exertion (3/7, 43%), or chest tightness (4/7, 57%), rather than sensory symptoms, were the initial symptoms in patients 7 and 8 (Table 1 ). GI symptoms were common and included chronic constipation, diarrhea or constipation alternating with diarrhea [ 5 , 7 ]. Chest tightness occurred particularly at night (with orthopnea).…”

Section: Resultsmentioning

confidence: 99%

Phenotypic expressions of hereditary Transthyretin Ala97Ser related Amyloidosis (ATTR) in Taiwanese

et al. 2017

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BackgroundThe disease course and early signs specific to ATTR Ala97Ser, the most common endemic mutation in Taiwan, have not been well described. Since new medications can slow down the rate of disease progression, the early diagnosis of this heterogeneous and fatal disease becomes critical.MethodsWe retrospectively reviewed the characteristics of genetically confirmed ATTR Ala97Ser patients at a tertiary referral medical center.ResultsEight patients from 7 different families were enrolled (61.7 ± 5.5 years). Gastrointestinal symptoms, dyspnea or chest tightness, rather than sensory symptoms, were the initial symptoms in two patients (2/7 = 29%). Body weight loss (3/7 = 43%), muscle wasting (4/7 = 57%), or dysphagia (3/7 = 43%) were the consecutive symptoms. Orthostatic symptoms including orthostatic hypotension (7/7 = 100%), dizziness (6/7 = 86%) and syncope (5/7 = 71%) tended to develop in the late phase of the disease. Autonomic dysfunction was conspicuous. Cardiographic findings included a combination of ventricular wall thickening and pericardial effusion (7/7 = 100%), a granular sparkling appearance of the ventricular myocardium (4/7 = 57%), or conduction abnormalities (5/7 = 71%).ConclusionsThis study broadens the recognition of the initial signs and symptoms, including cardiographic findings and longitudinal manifestations in Taiwanese individuals with ATTR Ala97Ser mutation. These manifestations should prompt doctors to perform further studies and make an early diagnosis.Electronic supplementary materialThe online version of this article (10.1186/s12883-017-0957-4) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Phenotypic expressions of hereditary Transthyretin Ala97Ser related Amyloidosis (ATTR) in Taiwanese

et al. 2017

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“…However, TTR‐FAP is now believed to have worldwide distribution (Benson and Kincaid, ) . More and more TTR‐FAP patients in Han Chinese people have been reported (Table ) (Yamamoto et al , ; Chou et al , ; Lachmann et al , ; Li et al , , ; Lim et al , ; Mak et al , , ; Liu et al , , , ; Yang et al , ; Chen et al , ; Zhang et al , , ; Long et al , ; Zou et al , ; Lv et al , ; Meng et al , ) . Here, we identified four different TTR heterozygous mutations already known to be associated with FAP in four unrelated families and among them, mutations Thr49Ala(p.Thr69Ala) and Tyr116Ser(p.Tyr136Ser) were detected for the first time in the Chinese population.…”

Section: Discussionmentioning

confidence: 99%

Clinical features of familial amyloid polyneuropathy carrying transthyretin mutations in four Chinese kindreds

Liu

Wang

et al. 2017

J Peripheral Nervous Sys

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Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is a rare hereditary disorder, characterized by a length-dependent polyneuropathy and dysfunction of various organs. Wide phenotypic heterogeneity makes early diagnosis difficult. In this study, we reviewed the clinical and electrophysiological features of four unrelated Chinese families with genetically confirmed TTR-FAP. Sequence analysis of TTR gene revealed the presence of four different mutations: Thr49Ala(p.Thr69Ala), Leu55Arg(p.Leu75Arg), Tyr116Ser(p.Tyr136Ser), and Ala36Pro(p.Ala56Pro) from six affected patients and two asymptomatic individuals. Two mutations, Thr49Ala(p.Thr69Ala) and Tyr116Ser(p.Tyr136 Ser), were detected in Chinese FAP patients for the first time. All affected patients manifested a progressive sensorimotor polyneuropathy starting in the lower limbs. The majority of the examined patients displayed cardiomyopathy and vitreous opacities. To avoid misdiagnosis, clinicians should consider screening for TTR variants in patients presenting with progressive polyneuropathy of undetermined origins.

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“…The reasons explaining the discrepancy may be that patients with TTR Gly83Arg mutant, indicating solitary ocular vitreous amyloidosis, without the evidence of systemic involvement, often came from the Department of Ophthalmology,[ 18 ] while Ala97Ser may be common in Chinese patients. [ 19 ] Some mutations indicating special clinical phenotypes such as familial carpal tunnel syndrome (Tyr114His) and predominant cardiomyopathy (Ala45Ser) proved the genotype-phenotype correlation,[ 20 21 ] while sometimes the same genotypes show different phenotypes just like the family of patient 5. The fact that there are large differences in penetrance in different populations may explain different family histories of our patients.…”

Section: Discussionmentioning

confidence: 99%

Hereditary Transthyretin Amyloidosis in Eight Chinese Families

Meng

Lyu

Zhang

et al. 2015

Chinese Medical Journal

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Background:Mutations of transthyretin (TTR) cause the most common type of autosomal-dominant hereditary systemic amyloidosis, which occurs worldwide. To date, more and more mutations in the TTR gene have been reported. Some variations in the clinical presentation are often observed in patients with the same mutation or the patients in the same family. The purpose of this study was to find out the clinicopathologic and genetic features of Chinese patients with hereditary TTR amyloidosis.Methods:Clinical and necessary examination materials were collected from nine patients of eight families with hereditary TTR amyloidosis at Peking University First Hospital from January 2007 to November 2014. Sural nerve biopsies were taken for eight patients and skin biopsies were taken in the calf/upper arm for two patients, for light and electron microscopy examination. The TTR genes from the nine patients were analyzed.Results:The onset age varied from 23 to 68 years. The main manifestations were paresthesia, proximal and/or distal weakness, autonomic dysfunction, cardiomyopathy, vitreous opacity, hearing loss, and glossohypertrophia. Nerve biopsy demonstrated severe loss of myelinated fibers in seven cases and amyloid deposits in three. One patient had skin amyloid deposits which were revealed from electron microscopic examination. Genetic analysis showed six kinds of mutations of TTR gene, including Val30Met, Phe33Leu, Ala36Pro, Val30Ala, Phe33Val, and Glu42Gly in exon 2.Conclusions:Since the pathological examinations of sural nerve were negative for amyloid deposition in most patients, the screening for TTR mutations should be performed in all the adult patients, who are clinically suspected with hereditary TTR amyloidosis.

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Transthyretin Ala97Ser in Chinese–Taiwanese patients with familial amyloid polyneuropathy: Genetic studies and phenotype expression

Cited by 27 publications

References 28 publications

Phenotypic expressions of hereditary Transthyretin Ala97Ser related Amyloidosis (ATTR) in Taiwanese

Phenotypic expressions of hereditary Transthyretin Ala97Ser related Amyloidosis (ATTR) in Taiwanese

Clinical features of familial amyloid polyneuropathy carrying transthyretin mutations in four Chinese kindreds

Hereditary Transthyretin Amyloidosis in Eight Chinese Families

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