{"title":"遗传性转甲状腺蛋白淀粉样变性患者纯合子和杂合子转甲状腺蛋白p.Val142Ile (V122I)变异的心脏受累、心外表现和结局的比较:一项队列研究","authors":"Grégoire Albenque, Mélanie Bézard, Mounira Kharoubi, Shirley Odouard, Ariane Lunati, Elsa Poullot, Amira Zaroui, Emmanuel Teiger, Luc Hittinger, Vincent Audard, Khalil El Karoui, Benoît Funalot, Pascale Fanen, Thibaud Damy, Silvia Oghina","doi":"10.1080/13506129.2023.2227322","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Hereditary transthyretin (ATTRv) p.Val142Ile (V122I) mutation is the most common inherited cause of cardiac amyloidosis and little is known about the phenotype and outcome of the rare homozygotic genotype. This study aimed to compare phenotypic characteristics and outcomes between heterozygous and homozygous patients with ATTRv V122I amyloidosis.</p><p><strong>Material and methods: </strong>This monocentric, observational, retrospective study conducted at the French National Referral Centre for Cardiac Amyloidosis (Henri Mondor Hospital, Créteil), described clinical, electrocardiographic, cardiac imaging features and prognostic data for patients with ATTRv V122I amyloidosis.</p><p><strong>Results: </strong>Among 185 ATTRv V122I patients identified, 161 were heterozygous and 24 were homozygous. The homozygous frequency was 13%. Onset occured significantly earlier in the homozygotes compared to heterozygotes with earlier median age at diagnosis (67[63-71] years vs 76[70-79] years, <i>p</i> < .001), age at first cardiac symptom (66[61-71] years vs 74[68-78] years, <i>p</i> < .001) and age at first extracardiac symptom (59[52-70] years vs 69[62-75] years, <i>p</i> = .003). Homozygous ATTRv V122I was also associated with greater disease burden with earlier events (death, transplant or hospitalisation for acute heart failure) compared with heterozygotes (71[67-74] vs 78[76-79] years, <i>p</i> = .018).</p><p><strong>Conclusion: </strong>This rare, homozygous V122I cohort confirmed the earlier age of onset, death and cardiac events in this population.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.2000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Comparison of cardiac involvement, extracardiac manifestations and outcomes between homozygote and heterozygote transthyretin p.Val142Ile (V122I) variant in patients with hereditary transthyretin amyloidosis: a cohort study.\",\"authors\":\"Grégoire Albenque, Mélanie Bézard, Mounira Kharoubi, Shirley Odouard, Ariane Lunati, Elsa Poullot, Amira Zaroui, Emmanuel Teiger, Luc Hittinger, Vincent Audard, Khalil El Karoui, Benoît Funalot, Pascale Fanen, Thibaud Damy, Silvia Oghina\",\"doi\":\"10.1080/13506129.2023.2227322\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Hereditary transthyretin (ATTRv) p.Val142Ile (V122I) mutation is the most common inherited cause of cardiac amyloidosis and little is known about the phenotype and outcome of the rare homozygotic genotype. This study aimed to compare phenotypic characteristics and outcomes between heterozygous and homozygous patients with ATTRv V122I amyloidosis.</p><p><strong>Material and methods: </strong>This monocentric, observational, retrospective study conducted at the French National Referral Centre for Cardiac Amyloidosis (Henri Mondor Hospital, Créteil), described clinical, electrocardiographic, cardiac imaging features and prognostic data for patients with ATTRv V122I amyloidosis.</p><p><strong>Results: </strong>Among 185 ATTRv V122I patients identified, 161 were heterozygous and 24 were homozygous. The homozygous frequency was 13%. Onset occured significantly earlier in the homozygotes compared to heterozygotes with earlier median age at diagnosis (67[63-71] years vs 76[70-79] years, <i>p</i> < .001), age at first cardiac symptom (66[61-71] years vs 74[68-78] years, <i>p</i> < .001) and age at first extracardiac symptom (59[52-70] years vs 69[62-75] years, <i>p</i> = .003). Homozygous ATTRv V122I was also associated with greater disease burden with earlier events (death, transplant or hospitalisation for acute heart failure) compared with heterozygotes (71[67-74] vs 78[76-79] years, <i>p</i> = .018).</p><p><strong>Conclusion: </strong>This rare, homozygous V122I cohort confirmed the earlier age of onset, death and cardiac events in this population.</p>\",\"PeriodicalId\":50964,\"journal\":{\"name\":\"Amyloid-Journal of Protein Folding Disorders\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2023-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Amyloid-Journal of Protein Folding Disorders\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/13506129.2023.2227322\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/6/28 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Amyloid-Journal of Protein Folding Disorders","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/13506129.2023.2227322","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/6/28 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景:遗传性转甲状腺素(ATTRv) p.Val142Ile (V122I)突变是心脏淀粉样变性最常见的遗传原因,对这种罕见的纯合子基因型的表型和预后知之甚少。本研究旨在比较杂合型和纯合型ATTRv V122I淀粉样变患者的表型特征和结果。材料和方法:这项在法国国家心脏淀粉样变性转诊中心(Henri Mondor医院,cr teil)进行的单中心、观察性、回顾性研究描述了attv V122I淀粉样变性患者的临床、心电图、心脏影像学特征和预后数据。结果:185例ATTRv V122I患者中,杂合161例,纯合24例。纯合子频率为13%。纯合子的发病时间明显早于诊断时中位年龄较早的杂合子(67[63-71]岁vs 76[70-79]岁,p p p = 0.003)。与杂合子相比,纯合子ATTRv V122I也与更大的疾病负担和更早的事件(死亡、移植或因急性心力衰竭住院)相关(71[67-74]对78[76-79]年,p = 0.018)。结论:这一罕见的纯合子V122I队列证实了该人群的发病年龄、死亡和心脏事件较早。
Comparison of cardiac involvement, extracardiac manifestations and outcomes between homozygote and heterozygote transthyretin p.Val142Ile (V122I) variant in patients with hereditary transthyretin amyloidosis: a cohort study.
Background: Hereditary transthyretin (ATTRv) p.Val142Ile (V122I) mutation is the most common inherited cause of cardiac amyloidosis and little is known about the phenotype and outcome of the rare homozygotic genotype. This study aimed to compare phenotypic characteristics and outcomes between heterozygous and homozygous patients with ATTRv V122I amyloidosis.
Material and methods: This monocentric, observational, retrospective study conducted at the French National Referral Centre for Cardiac Amyloidosis (Henri Mondor Hospital, Créteil), described clinical, electrocardiographic, cardiac imaging features and prognostic data for patients with ATTRv V122I amyloidosis.
Results: Among 185 ATTRv V122I patients identified, 161 were heterozygous and 24 were homozygous. The homozygous frequency was 13%. Onset occured significantly earlier in the homozygotes compared to heterozygotes with earlier median age at diagnosis (67[63-71] years vs 76[70-79] years, p < .001), age at first cardiac symptom (66[61-71] years vs 74[68-78] years, p < .001) and age at first extracardiac symptom (59[52-70] years vs 69[62-75] years, p = .003). Homozygous ATTRv V122I was also associated with greater disease burden with earlier events (death, transplant or hospitalisation for acute heart failure) compared with heterozygotes (71[67-74] vs 78[76-79] years, p = .018).
Conclusion: This rare, homozygous V122I cohort confirmed the earlier age of onset, death and cardiac events in this population.
期刊介绍:
Amyloid: the Journal of Protein Folding Disorders is dedicated to the study of all aspects of the protein groups and associated disorders that are classified as the amyloidoses as well as other disorders associated with abnormal protein folding. The journals major focus points are:
etiology,
pathogenesis,
histopathology,
chemical structure,
nature of fibrillogenesis;
whilst also publishing papers on the basic and chemical genetic aspects of many of these disorders.
Amyloid is recognised as one of the leading publications on amyloid protein classifications and the associated disorders, as well as clinical studies on all aspects of amyloid related neurodegenerative diseases and major clinical studies on inherited amyloidosis, especially those related to transthyretin. The Journal also publishes book reviews, meeting reports, editorials, thesis abstracts, review articles and symposia in the various areas listed above.