First description of Portuguese patients with cardiac amyloidosis and p.Val142Ile: more evidence of an “African variant” in Caucasians

Figures & data

Table 1. Proband’s individual characteristics at diagnosis.

	Patient 1	Patient 2	Patient 3
Diagnoses’ age	73	69	66
Val142Ile-zigosity	Val142Ile Heterozygous	Val142Ile Heterozygous	Val142Ile Homozygous
Other organ dysfunction	CKD, III; Liver dysfunction	–	CKD, IV; Liver dysfunction
Cardiovascular risk factors	Arterial hypertension Diabetes mellitus	Smoking habits
Carpal tunnel syndrome	Yes (bilateral surgery 20 years earlier to diagnosis)	Yes (bilateral surgery 5 years earlier to diagnosis)	–
Cardiac presentation	CHF	CHF	CHF
Septum Hypertrophy (mm)	22	20	18
Initial LVEF (%)	55	60	65
Last LVEF (%)	32	48	39
Pulmonary artery pressure (mmHg)	50	32	54
Cardiac magnetic resonance LGE findings	Extensive intramyocardial LGE on LV and RV	–	–
Time to first hospitalization (year)	2	3	1
Rhythm disturbance	Advanced AVB; AF	Advanced AVB	–
Tafamidis	Approved	Waiting for approval	Refused

AF: atrial fibrillation; AVB: atrioventricular block; CHF: congestive heart failure; CKD: chronic kidney dysfunction; LGE - late gadolinium enhancement LV: left ventricle; LVEF: left ventricle ejection fraction; RV: righ ventricle.

Figure 1. Genogram of patient 1 (A) and patient 3 (B).

Figure 2. Summary map of previous reports of Caucasian patients with the Val142Ile ATTRv.

Table 2. Resume of Caucasian p.Val142Ile cases published.

Author	Gillmore et al. [10]	Hamidi et al. [11]	Ammirati et al. [12]	Swiecicki et al. [13]	Cappelli et al. [14]	Marrero Negrin et al. [16]	Gentile et al. [15]						Rasmussen et al. [17]	Trachtenberg et al. [18]
Publication Year	1991	2001	2012	2015	2016	2019	2020						2022	2022
Number of patients identified/study	1	1	1	5	5	1	6						1	25
Mean diagnoses’ age	83	76	64	UK	73	57	65						71	UK
Gender	Male	Male	Male	UK	UK	Male	UK						Male	UK
Val142Ile-zigosity	Het	Het	Het	UK	UK	Homo	Het	Het	Homo	Het	Het^b	Het	Het	UK
Presentation	CHF	CHF	CHF	UK	UK	CHF	CHF	CHF	NP	CHF	NP	CHF	CHF	UK
NYHA	II	II	II-III	UK	II- III	II	II	II	IV	II	II	II	II	UK
Other organ dysfunction	–	–	–	UK	UK	–	MO	–	–	–	–	Renal	–	UK
Carpal tunnel syndrome	–	Yes	–	UK	UK	Yes	Yes	Yes	Yes	Yes	–	Yes	Yes	UK
Mean septum hypertrophy, grade or mm	UK	16.2	Moderate	UK	18	19	17						15	UK
Mean LV function, grade or LVEF (%)	Normal	Normal	Normal	UK	36	54	UK						52	UK
Months to first hospitalization	UK	UK	14	UK	UK	5	UK						–	UK
Arrythmia/PM	AF	1st AVB	Hemi block	UK	UK	UK	PM	PM	–	–	–	PM	–	UK
Follow up	UK	UK	Cardiac Transplant	UK	UK	UK	D	–	–	–	D	D	–	UK
Tafamidis	NA	NA	NA	NA	UK	UK	Yes	–	–	–	–	Yes	–	UK
Number of family cases identified/study	0	1	2	UK	UK	1^a	5						1	UK
Number of family carriers identified/study	2	1	3	UK	UK	6 (1^a)	3						1	UK

^aV122I homozygous; ^bV122I homo/E89Q compound heterozygous. AF: atrial fibrillation; AVB: atrio ventricle block; CTS: carpal tunnel syndrome; D: Death; LV: left ventricle; Het: Heterozygous; Homo: homozygosity; MO: multiorgan dysfunction; NA: not applicable; NP: Neuropathy; PM: pacemaker; UK: unknow.

Gillmore JD, Booth DR, Pepys MB, et al. Hereditary cardiac amyloidosis associated with the transthyretin Ile122 mutation in a white man. Heart. 1999;82(3):e2.

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Hamidi K, Nakamura M, Yamashita T, et al. Cardiac amyloidosis associated with the transthyretin Ile122 mutation in a caucasian family. Amyloid. 2001;8(4):263–269.

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Ammirati E, Marziliano N, Vittori C, et al. The first caucasian patient with p.Val122Ile mutated-transthyretin cardiac amyloidosis treated with isolated heart transplantation. Amyloid. 2012;19(2):113–117.

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Swiecicki PL, Zhen DB, Mauermann ML, et al. Hereditary ATTR amyloidosis: a single-institution experience with 266 patients. Amyloid. 2015;22(2):123–131.

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Cappelli F, Frusconi S, Bergesio F, et al. The Val142Ile transthyretin cardiac amyloidosis: not only an Afro-American pathogenic variant? A single-Centre italian experience. J Cardiovasc Med (Hagerstown). 2016;17(2):122–125.

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Marrero Negrin N, Medina Gil JM, Garcia Cruz ML, et al. Transthyretin cardiac amyloidosis due to homozygous Val122Ile mutation in a caucasian man. Rev Esp Cardiol. 2019;72(12):1086–1088.

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Gentile L, Di Bella G, Minutoli F, et al. Description of a large cohort of caucasian patients with V122I ATTRv amyloidosis: neurological and cardiological features. J Peripher Nerv Syst. 2020;25(3):273–278.

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Rasmussen TBL, Dybro BT, Clemmensen AM, et al. Transthyretin gene variants and associated phenotypes in danish patients with amyloid cardiomyopathy. Cardiogenetics. 2022;12(1):1–11.

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Trachtenberg BH, Shah SK, Nussbaum RL, et al. Presence of the V122I variant of hereditary Transthyretin-Mediated amyloidosis Among Self-Reported white individuals in a sponsored genetic testing program. Circ Genom Precis Med. 2021;14(5):e003466.

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