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Abstract：
BACKGROUND: In Argentina, there is limited data of prevalence of variant transthyretin amyloidosis (ATTRv) and phenotype-genotype correlation. The laboratory of Hospital Italiano de Buenos Aires (HIBA) is a reference center for transthyretin (TTR) gene sequencing. The Institutional Amyloidosis Registry (RIA) enable us to characterize people with ATTRv. Our aim was to describe the prevalence of TTR mutations at a reference center in Argentina and the phenotypic presentations of patients with ATTRv included in an institutional registry.
METHODS: Retrospective cohort study of consecutive patients with genetic variants in the TTR gene identified from 2012 to 2019 in the laboratory. We collected all phenotypic characteristics of patients who were clinically evaluated by HIBA doctors.
RESULTS: Five hundred seventy-six patients tested, 141 positive: p.Val50Met 107, p.Thr80Ala 16, p.Ala117Ser 9, p.Phe84Leu 2, p.Ile127Val 2, p.Tyr134Cys 2, p.Ala56Pro 2, p.Val142Ile 1. Only 20 patients were clinically evaluated. The mean age at diagnosis was 54 years; 70% had family history with a pedigree median of 4. Mutations were p.Thr80Ala 9, p.Val50Met 6, p.Ala56Pro 2, p.Val142Ile 1, p.Phe84Leu 1, and p.Tyr134Cys 1. Eleven patients presented polyneuropathy, 11 had gastrointestinal compromise, six patients had autonomic compromise, six presented cardiac symptoms and four patients presented ocular involvement.
CONCLUSIONS: We present the first prevalence report of TTR mutations in a reference center of amyloidosis in Argentina. The most frequent genetic variant was p.Val50Met. Our data show considerable phenotypic heterogeneity in the patients with ATTRv.
METHODS: Retrospective cohort study of consecutive patients with genetic variants in the TTR gene identified from 2012 to 2019 in the laboratory. We collected all phenotypic characteristics of patients who were clinically evaluated by HIBA doctors.
RESULTS: Five hundred seventy-six patients tested, 141 positive: p.Val50Met 107, p.Thr80Ala 16, p.Ala117Ser 9, p.Phe84Leu 2, p.Ile127Val 2, p.Tyr134Cys 2, p.Ala56Pro 2, p.Val142Ile 1. Only 20 patients were clinically evaluated. The mean age at diagnosis was 54 years; 70% had family history with a pedigree median of 4. Mutations were p.Thr80Ala 9, p.Val50Met 6, p.Ala56Pro 2, p.Val142Ile 1, p.Phe84Leu 1, and p.Tyr134Cys 1. Eleven patients presented polyneuropathy, 11 had gastrointestinal compromise, six patients had autonomic compromise, six presented cardiac symptoms and four patients presented ocular involvement.
CONCLUSIONS: We present the first prevalence report of TTR mutations in a reference center of amyloidosis in Argentina. The most frequent genetic variant was p.Val50Met. Our data show considerable phenotypic heterogeneity in the patients with ATTRv.
摘要：
背景：在阿根廷，关于变异型甲状腺素运载蛋白淀粉样变性(ATTRv)的患病率和表型-基因型相关性的数据有限.意大利布宜诺斯艾利斯医院（HIBA）的实验室是转甲状腺素蛋白（TTR）基因测序的参考中心。机构淀粉样变性注册（RIA）使我们能够表征ATTRv患者。我们的目的是描述阿根廷参考中心的TTR突变的患病率以及机构注册表中包含的ATTRv患者的表型表现。
方法：回顾性队列研究，对2012年至2019年在实验室中发现的TTR基因遗传变异的连续患者进行研究。我们收集了由HIBA医生进行临床评估的患者的所有表型特征。
结果：测试了576名患者，141阳性：p.Val50Met107，p.Thr80Ala16，p.Ala117Ser9，p.Phe84Leu2，p.Ile127Val2，p.Tyr134Cys2，p.Ala56Pro2，p.Val142Ile1。仅对20例患者进行了临床评估。诊断时的平均年龄为54岁；70％有家族史，家谱中位数为4。突变为p.Thr80Ala9，p.Val50Met6，p.Ala56Pro2，p.Val142Ile1，p.Phe84Leu1和p.Tyr134Cys1。11例患者出现多发性神经病,11人胃肠道受损，六名患者自主神经受损，6例患者出现心脏症状,4例患者出现眼部受累.
结论：我们在阿根廷一个淀粉样变性参考中心首次报道了TTR突变的患病率。最常见的遗传变异是p.Val50Met。我们的数据显示ATTRv患者的表型异质性相当大。
方法：回顾性队列研究，对2012年至2019年在实验室中发现的TTR基因遗传变异的连续患者进行研究。我们收集了由HIBA医生进行临床评估的患者的所有表型特征。
结果：测试了576名患者，141阳性：p.Val50Met107，p.Thr80Ala16，p.Ala117Ser9，p.Phe84Leu2，p.Ile127Val2，p.Tyr134Cys2，p.Ala56Pro2，p.Val142Ile1。仅对20例患者进行了临床评估。诊断时的平均年龄为54岁；70％有家族史，家谱中位数为4。突变为p.Thr80Ala9，p.Val50Met6，p.Ala56Pro2，p.Val142Ile1，p.Phe84Leu1和p.Tyr134Cys1。11例患者出现多发性神经病,11人胃肠道受损，六名患者自主神经受损，6例患者出现心脏症状,4例患者出现眼部受累.
结论：我们在阿根廷一个淀粉样变性参考中心首次报道了TTR突变的患病率。最常见的遗传变异是p.Val50Met。我们的数据显示ATTRv患者的表型异质性相当大。
