Hereditary ATTR Amyloidosis with Cardiomyopathy Caused by the Novel Variant Transthyretin Y114S (p.Y134S)

Nakase, Taku; Yamashita, Taro; Matsuo, Yoshimasa; Nomura, Toshiya; Sasada, Keiko; Masuda, Teruaki; Misumi, Yohei; Takamatsu, Koutaro; Oda, Shigeto; Furukawa, Yoshiyuki; Obayashi, Konen; Matsui, Hirotaka; Ando, Yukio; Ueda, Mitsuharu

doi:10.2169/internalmedicine.2456-18

Cited by 6 publications

(4 citation statements)

References 17 publications

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“…Patients with ATTRv amyloidosis had diverse disease manifestations including polyneuropathy, cardiomyopathy, carpal tunnel syndrome, vitreous opacity, and dementia, according to genetic phenotype and environmental factors. This study found several patients with new mutations in the TTR gene 18,27,28…”

Section: Discussionmentioning

confidence: 65%

“…This study found several patients with new mutations in the TTR gene. 18,27,28 Therefore, in this study we reported the different types of amyloidosis and the manifestations of the disease at diagnosis for patients who were referred to our center. These data may contribute to early diagnosis and early intervention to improve the treatment and care of patients with amyloidosis.…”

Section: Re Sultsmentioning

confidence: 99%

“…17 We performed a genetic analysis via purification of genomic DNA from blood leukocytes, after which we sequenced the TTR gene (forward and reverse sequences). 18 We also performed matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with serum TTR so that we could identify variant TTR peaks with a changed mass as well as the wild-type TTR peak. 19 We determined mutations by using amino acid codes and sequence numbers of mature proteins as done in amyloid protein studies.…”

Section: Patients and Me Thodsmentioning

confidence: 99%

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Clinical, pathological, and proteomic characteristics of newly diagnosed amyloidosis patients: Experience from a single referral center in Japan

Ando

Yamashita

Misumi

et al. 2020

Neurology & Clinical Neurosc

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Novel therapies have recently been used for different amyloidoses including hereditary transthyretin (ATTR, ATTRv) amyloidosis, wild‐type ATTR (ATTRwt) amyloidosis, immunoglobulin light chain (AL)amyloidosis, and amyloid A (AA) amyloidosis. Early, accurate diagnosis is important for improved prognosis and cure. However, early intervention with early diagnosis is often difficult, because these diseases are frequently difficult to identify given their phenotypic heterogeneity. This study aimed to analyze characteristics of patients with amyloidosis that was diagnosed at the Amyloidosis Medical Practice Center, Kumamoto University Hospital, which, as an amyloidosis center in Japan, conducts histopathological, proteomic, and genetic analyses of amyloidosis. We analyzed diagnostic results and disease manifestations of patients diagnosed during April 2012 and March 2019. This study reviewed 1937 consecutive consultations that provided clinical information. The patients’ average age was 65.9 (median 69) years. Of all patients, 66.6% were male. Diagnoses included ATTRv: 13.4%, ATTRwt: 14.3%, ATTR (no genetic analysis consultation requested): 4.6%, ALλ: 19.7%, ALκ: 8.8%, AA: 3.0%, β2‐microglobulin (dialysis‐related): 0.8%, and others: 1.9%, no TTR gene mutation (no histopathological analysis consultation requested): 23.2% (including duplicate consultations). ATTRv amyloidosis cases included V30M in endemic areas: 7.4%, V30M in non‐endemic areas: 51.2%, and non‐V30M: 41.4%. Sixty‐six cases required laser microdissection and liquid chromatography‐tandem mass spectrometry. Initial manifestations included polyneuropathy: 13.2%, carpal tunnel syndrome: 5.6%, autonomic dysfunction: 2.7%, heart failure: 28.4%, cardiac hypertrophy: 2.2%, arrhythmia: 5.0%, renal impairment: 11.1%, and stroke: 1.8%. Amyloidosis types and manifestations were diverse. For early diagnosis and appropriate interventions, improved diagnostic systems are needed.

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Section: Discussionmentioning

confidence: 65%

Section: Re Sultsmentioning

confidence: 99%

Section: Patients and Me Thodsmentioning

confidence: 99%

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Clinical, pathological, and proteomic characteristics of newly diagnosed amyloidosis patients: Experience from a single referral center in Japan

Ando

Yamashita

Misumi

et al. 2020

Neurology & Clinical Neurosc

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“…Наследственный ATTR-амилоидоз бывает результатом мутации в гене (расположенном на 18q хромосоме и состоящем из 4 экзонов), кодирующем транстиретин, что приводит к замене аминокислот в его молекуле [10]. На сегодняшний день зарегистрировано более 140 различных мутаций в гене транстиретина, большинство из мутаций амилоидогенны, лишь около 10 считаются неамилоидогенными [10,11]. Большинство пациентов являются гетерозиготами, поэтому в организме имеют не только мутантный, а еще нормальный немутантный транстиретин.…”

Section: Introductionunclassified

A Clinical Case of the Hereditary Transthyretin Amyloidosis

Резник

Нгуен

Борисовская

et al. 2021

Arhivʺ vnutrennej mediciny

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Introduction: Transthyretin (ATTR) amyloidosis is a severe rare disease with wide range of characters without specific symptoms including the damage to the peripheral nervous system and cardiac involvement. Case report: A 60-year-old female patient represented with weakness and paresthesia in the distal parts of the lower limbs, impeding walking for 2 years. Initially, symptoms were considered as a manifestation of degenerative stenosis of the lumbar spine, decompressive laminectomy was performed but the symptoms after surgical treatment persisted. Based on data from clinical and electroneuromyographic examinations, axonal sensorimotor polyneuropathy was diagnosed. Genetic testing of the patient, her elder sister, son and daughter using the Sanger sequencing method detected a variant of the nucleotide sequence in the fourth exon of the transthyretin gene (Chr18: 29178562, rs148538950, NM_000371.3: c.G368A: p. Arg123His) in the heterozygous state. A subcutaneous fatty tissue biopsy of abdominal wall with a Congo red stain and polarized light examination revealed amyloid microdeposits, grade CR 1+ (minimal deposits), confirmed the diagnosis of familial ATTR-amyloidosis. Echocardiography revealed concentric left ventricular wall thickening with normal end diastolic size and volume, preserved ejection fraction, left atrial enlargement, pulmonary hypertension and type 1 diastolic dysfunction. Specific anti-amyloid therapy — tafamidis was prescribed. Conclusion: In patients with peripheral polyneuropathy and left ventricular hypertrophy of unknown etiology, a complex examination is necessary for the timely detection and treatment of amyloid polyneuropathy and cardiomyopathy.

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Cardiomyopathy: pathogenesis and therapeutic interventions

Huang,

Li,

et al. 2024

MedComm

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Cardiomyopathy is a group of disease characterized by structural and functional damage to the myocardium. The etiologies of cardiomyopathies are diverse, spanning from genetic mutations impacting fundamental myocardial functions to systemic disorders that result in widespread cardiac damage. Many specific gene mutations cause primary cardiomyopathy. Environmental factors and metabolic disorders may also lead to the occurrence of cardiomyopathy. This review provides an in‐depth analysis of the current understanding of the pathogenesis of various cardiomyopathies, highlighting the molecular and cellular mechanisms that contribute to their development and progression. The current therapeutic interventions for cardiomyopathies range from pharmacological interventions to mechanical support and heart transplantation. Gene therapy and cell therapy, propelled by ongoing advancements in overarching strategies and methodologies, has also emerged as a pivotal clinical intervention for a variety of diseases. The increasing number of causal gene of cardiomyopathies have been identified in recent studies. Therefore, gene therapy targeting causal genes holds promise in offering therapeutic advantages to individuals diagnosed with cardiomyopathies. Acting as a more precise approach to gene therapy, they are gradually emerging as a substitute for traditional gene therapy. This article reviews pathogenesis and therapeutic interventions for different cardiomyopathies.

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Hereditary ATTR Amyloidosis with Cardiomyopathy Caused by the Novel Variant Transthyretin Y114S (p.Y134S)

Cited by 6 publications

References 17 publications

Clinical, pathological, and proteomic characteristics of newly diagnosed amyloidosis patients: Experience from a single referral center in Japan

Clinical, pathological, and proteomic characteristics of newly diagnosed amyloidosis patients: Experience from a single referral center in Japan

A Clinical Case of the Hereditary Transthyretin Amyloidosis

Cardiomyopathy: pathogenesis and therapeutic interventions

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