A rare variant in the TTR gene (p.E112K) is associated with systemic amyloidosis and a new symptom – skin hyperemia in response to ethanol intake: family segregation analysis, literature review, and a clinical case. Case report

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Abstract

Transthyretin amyloidosis (ATTR-amyloidosis) is a systemic disorder associated with extracellular deposition in the tissues and organs of amyloid fibrils, transthyretin-containing insoluble protein-polysaccharide complexes. The change in transthyretin conformation, leading to its destabilization and amyloidogenicity, can be acquired (wild type, ATTRwt) and hereditary due to mutations in the TTR gene (variant, ATTRv) [1, 2]. Hereditary ATTR-amyloidosis has an earlier onset and greater phenotypic diversity. The age of the manifestation, the predominant phenotype, and the prognosis are often determined by the genetic variant. To date, more than 140 variants in the TTR gene have been identified; however, most of them are described in single patients and do not have clear evidence of pathogenicity. The prospects of a new pathogenetic treatment of ATTR-amyloidosis [3], especially effective in the early stages of the disease, increases the relevance of timely diagnosis, which is challenging due to physicians' lack of awareness. This article presents a clinical case of ATTRv-amyloidosis associated with a rare pathogenic variant in the TTR gene and a newly described skin symptom. This article is a literature review.

About the authors

Olga S. Chumakova

Central State Medical Academy of the President of the Russian Federation; City Clinical Hospital №17

Author for correspondence.
Email: chumakovaolga@bk.ru
ORCID iD: 0000-0003-2373-1183

канд. мед. наук, доц. каф. терапии, кардиологии и функциональной диагностики с курсом нефрологии ФГБУ ДПО ЦГМА УД Президента РФ, врач-кардиолог ГБУЗ «ГКБ №17»

Russian Federation, Moscow; Moscow

Svetlana N. Nasonova

Chazov National Medical Research Center of Cardiology

Email: chumakovaolga@bk.ru
ORCID iD: 0000-0002-0920-7417

канд. мед. наук, ст. науч. сотр. отд. заболеваний миокарда и сердечной недостаточности 

Russian Federation, Moscow

Yulia V. Frolova

Petrovsky National Research Centre of Surgery

Email: chumakovaolga@bk.ru
ORCID iD: 0000-0002-2075-8543

доктор мед. наук, вед. науч. сотр. отд. хирургического лечения дисфункций миокарда и сердечной недостаточности

Russian Federation, Moscow

Elena A. Stepanova

Buyanov City Clinical Hospital; Russian Medical Academy of Continuous Professional Education

Email: chumakovaolga@bk.ru
ORCID iD: 0000-0001-7760-5858

врач-патологоанатом ГБУЗ «ГКБ им. В.М. Буянова», ассист. каф. патологической анатомии

Russian Federation, Moscow; Moscow

Elena A. Mershina

Lomonosov Moscow State University

Email: chumakovaolga@bk.ru
ORCID iD: 0000-0002-1266-4926

канд. мед. наук, зав. отделением рентгенодиагностики

Russian Federation, Moscow

Valentin E. Sinitsyn

Lomonosov Moscow State University

Email: chumakovaolga@bk.ru
ORCID iD: 0000-0002-5649-2193

доктор мед. наук, проф., зав. каф. лучевой диагностики и лучевой терапии фак-та фундаментальной медицины, рук. отд. лучевой диагностики университетской клиники Медицинского научно-образовательного центра

Russian Federation, Moscow

Dmitry A. Zateyshchikov

Central State Medical Academy of the President of the Russian Federation

Email: chumakovaolga@bk.ru
ORCID iD: 0000-0001-7065-2045

доктор мед. наук, проф., зав. каф. терапии, кардиологии и функциональной диагностики с курсом нефрологии

Russian Federation, Moscow

Igor V. Zhirov

Chazov National Medical Research Center of Cardiology; Russian Medical Academy of Continuous Professional Education

Email: chumakovaolga@bk.ru
ORCID iD: 0000-0002-4066-2661

доктор мед. наук, вед. науч. сотр. отд. заболеваний миокарда и сердечной недостаточности ФГБУ «НМИЦ кардиологии им. акад. Е.И. Чазова», проф. каф. Кардиологии ФГБОУ ДПО РМАНПО

Russian Federation, Moscow; Moscow

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Supplementary files

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2. Fig. 1. a – electrocardiogram; b – echocardiogram; c – magnetic resonance imaging of the heart (delayed contrast enhancement, IR sequence with suppression of the signal from the myocardium).

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3. Fig. 2. Slides with heart biopsy specimen, Congo red staining, ×200:

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4. Fig. 3. Family tree with cosegregation analysis of the TTR p.E112K variant with amyloidosis.

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5. Fig. 4. Chronology of symptoms and diagnosis of ATTRv-amyloidosis.

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