Familial Transthyretin Amyloidosis with Variant Asp38Ala Presenting with Orthostatic Hypotension and Chronic Diarrhea

Cho, Hyun Jun; Yoon, Jae Yong; Bae, Myung Hwan; Lee, Jang Hoon; Yang, Dong Heon; Park, Hun Sik; Cho, Yongkeun; Chae, Shung Chull; Jun, Jae Eun

doi:10.4250/jcu.2012.20.4.209

Cited by 7 publications

(10 citation statements)

References 21 publications

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“…This study is the first investigation into the phenotypic characteristics and molecular genetics of hereditary ATTR in Korea. Based on a comprehensive review of this study and previous Korean reports (Cho et al., , Ryu et al., ), the majority of the Korean patients with hereditary ATTR had a mixed (cardiac/neurologic) phenotype (78%, 7/9; Table ). Although the number of hereditary ATTR patients identified in this study was limited, the data supported the finding that the D58A genetic variant is a predominant mutation of the TTR gene among Koreans (56%, 5/9; Table ).…”

Section: Discussionmentioning

confidence: 70%

“…Currently, insufficient data are available on the spectrum of mutations in Korean patients. There are only two documented Korean cases of hereditary ATTR based on molecular genetic studies to date (Ryu et al., ; Cho et al., ). Our aim in this study was to investigate the phenotypic and genotypic spectra of hereditary ATTR in Korean patients.…”

Section: Introductionmentioning

confidence: 99%

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Asp58Ala is the Predominant Mutation of the TTR Gene in Korean Patients with Hereditary Transthyretin‐Related Amyloidosis

Jang

Lee

Kım

et al. 2015

Annals of Human Genetics

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SummaryHereditary transthyretin (TTR)-related amyloidosis (ATTR) seems to be a rare autosomal-dominant inherited form of systemic amyloidosis. Studies indicate considerable heterogeneity in the disease's presentation and genotype; however, there is little data from Korea, where the prevalence of hereditary ATTR is very low. In this study, we investigated the phenotypic and genotypic spectra of hereditary ATTR in Korea. Direct sequencing analysis was performed to detect TTR gene mutations in amyloidosis patients whose results of TTR immunohistochemical staining were positive or equivocal. Clinical presentation was categorized as exclusively cardiac, exclusively neurologic, or mixed phenotype. Of 12 genetic tests performed, seven were positive for TTR mutations. D58A (c.173A>C) was the most common mutation in this study (57%, 4/7). The majority of those patients with hereditary ATTR had the mixed phenotype (86%, 6/7). The patients with D58A mutation had older ages of disease onset (median, 61 years vs. 42 years; P = 0.08), and a higher incidence of gastrointestinal involvement (75% vs. 0%; P = 0.03) than those with other identified TTR mutations. A significant male predominance was also noted in this study (P = 0.01).

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Section: Discussionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Asp58Ala is the Predominant Mutation of the TTR Gene in Korean Patients with Hereditary Transthyretin‐Related Amyloidosis

Jang

Lee

Kım

et al. 2015

Annals of Human Genetics

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“…The first patient presented a late onset, mainly small fiber painful neuropathy associated with cardiac amyloidosis. Interestingly, her clinical presentation is very similar to that found in patients with other mutations in the same amino acid (Yazaki et al ., ; Cho et al ., ) . These manifestations (late onset small fiber neuropathy plus cardiac amyloidosis) may constitute a typical pattern of mutations occurring in this amino acid at the TTR protein.…”

Section: Nerve Conduction Studiesmentioning

confidence: 97%

Transthyretin Asp38Tyr: a new mutation associated to a late onset neuropathy

Moreira

Marques

Lourenço

et al. 2015

J Peripheral Nervous Sys

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“…This p.D58A sequence change replaces the aspartic acid at codon 58 with alanine [41]. The p.D58A pathogenic alteration has been observed in numerous persons affected with ATTRv and is a predominant cause of ATTRv in Korea [42][43][44]. Other variants that disrupt the same residue (c.173A[T [p.D58V] and c.172G[T [p.D58Y]) have been observed in affected persons [45,46], suggesting that it is a significant residue and that disruption is likely to be causative of disease.…”

Section: Collection Of Supportive Clinical Datamentioning

confidence: 99%

Three Newly Recognized Likely Pathogenic Gene Variants Associated with Hereditary Transthyretin Amyloidosis

et al. 2022

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Introduction: Hereditary transthyretin amyloidosis (ATTRv [variant]) is a clinically heterogeneous, progressively debilitating, fatal disease resulting from the deposition of insoluble amyloid fibrils in various organs and tissues. Early diagnosis of ATTRv can be facilitated with genetic testing; however, such testing of the TTR gene identifies variants of uncertain significance (VUS) in a minority of cases, a small percentage of which have the potential to be pathogenic. The Akcea/Ambry VUS Initiative is dedicated to gathering molecular, clinical, and inheritance data for each TTR VUS identified by genetic testing programs to reclassify TTR variants to a clinically actionable status (e.g., variant likely pathogenic [VLP]) where appropriate. Methods: Classification criteria used here, based on recommendations from the American College of Medical Genetics and Genomics, are stringent and comprehensive, requiring distinct lines of evidence supporting pathogenesis. Results: Three TTR variants have been reclassified from VUS to VLP, including c.194C[T (p.A65V), c.172G[C (p.D58H), and c.239C[T (p.T80I). In each case, the totality of genetic, structural, and clinical evidence provided strong support for pathogenicity. Conclusions: Based on several lines of evidence, three TTR VUS were reclassified as VLP, resulting in a high likelihood of disease diagnosis for those and subsequent patients as well as at-risk family members.

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Familial Transthyretin Amyloidosis with Variant Asp38Ala Presenting with Orthostatic Hypotension and Chronic Diarrhea

Cited by 7 publications

References 21 publications

Asp58Ala is the Predominant Mutation of the TTR Gene in Korean Patients with Hereditary Transthyretin‐Related Amyloidosis

Asp58Ala is the Predominant Mutation of the TTR Gene in Korean Patients with Hereditary Transthyretin‐Related Amyloidosis

Transthyretin Asp38Tyr: a new mutation associated to a late onset neuropathy

Three Newly Recognized Likely Pathogenic Gene Variants Associated with Hereditary Transthyretin Amyloidosis

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