ATTRV122I amyloidosis

General Information (adopted from Orphanet):

Synonyms, Signs: FAP AMYLOIDOSIS, LEPTOMENINGEAL, TRANSTHYRETIN-RELATED, INCLUDED
HEREDITARY AMYLOIDOSIS, TRANSTHYRETIN-RELATED
AMYLOID POLYNEUROPATHY, FAMILIAL
AMYLOID CARDIOMYOPATHY, TRANSTHYRETIN-RELATED, INCLUDED
TRANSTHYRETIN AMYLOIDOSIS
TTR-related cardiac amyloidosis
TTR-related amyloid cardiomyopathy
Transthyretin amyloid cardiopathy
ATTR cardiomyopathy
Transthyretin-related familial amyloid cardiomyopathy
Number of Symptoms 29
OrphanetNr: 85451
OMIM Id: 105210
ICD-10: E85.0
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal dominant
26610878 [IBIS]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Familial restrictive cardiomyopathy
 -Rare cardiac disease
 -Rare genetic disease
Familial transthyretin-related amyloidosis
 -Rare genetic disease
 -Rare systemic or rheumatologic disease

Comment:

The V122I variant is a common mutation in African Americans. The heterozygote frequency is approximately 4% in African Americans (PMID:24184229). The median survival from diagnosis for patients with ATTRm (V122I) was 25.6 months vs 43.0 months for ATTRwt (senile amyloidosis). ATTRm disease caused by V122I appears to confer a particularly high mortality (PMID:22877808).

Symptom Information: Sort by abundance 

1
(HPO:0001638) Cardiomyopathy Very frequent [IBIS] 100% (n=32) 19781421 IBIS 192 / 7739
2
(HPO:0200126) Amyolid cardiomyopathy Very frequent [IBIS] 100% (n=17) 19781421 IBIS 2 / 7739
3
(HPO:0003116) Abnormal echocardiogram Very frequent [IBIS] 100% (n=30) 19781421 IBIS 33 / 7739
4
(HPO:0011675) Arrhythmia Very frequent [IBIS] 100% (n=29) 19781421 IBIS 226 / 7739
5
(HPO:0200128) Biventricular hypertrophy 22877808 IBIS 11 / 7739
6
(HPO:0002875) Exertional dyspnea Frequent [IBIS] 83% (n=29) 19781421 IBIS 29 / 7739
7
(HPO:0006683) Abnormal ventricular filling Frequent [IBIS] 38% (n=11) 22877808 IBIS 5 / 7739
8
(HPO:0001667) Right ventricular hypertrophy Very frequent [IBIS] 100% (n=26) 19781421 IBIS 23 / 7739
9
(HPO:0001671) Abnormality of the cardiac septa 26610878 IBIS 55 / 7739
10
(HPO:0001698) Pericardial effusion Frequent [IBIS] 50% (n=24) 19781421 IBIS 20 / 7739
11
(HPO:0012664) Reduced ejection fraction 26610878 IBIS 32 / 7739
12
(HPO:0005110) Atrial fibrillation Occasional [IBIS] 28% (n=29) 19781421 IBIS 71 / 7739
13
(HPO:0001692) Primary atrial arrhythmia 26610878 IBIS 16 / 7739
14
(HPO:0001635) Congestive heart failure Very frequent [IBIS] 93% (n=29) 19781421 IBIS 232 / 7739
15
(HPO:0010741) Edema of the lower limbs 26610878 IBIS 34 / 7739
16
(HPO:0001278) Orthostatic hypotension Rare [IBIS] 7% (n=28) 19781421 IBIS 24 / 7739
17
(HPO:0012670) Orthostatic syncope 26610878 IBIS 2 / 7739
18
(HPO:0012398) Peripheral edema Frequent [IBIS] 66% (n=29) 19781421 IBIS 12 / 7739
19
(HPO:0003546) Exercise intolerance 22877808 IBIS 62 / 7739
20
(HPO:0003477) Peripheral axonal neuropathy Occasional [IBIS] 22877808 IBIS 62 / 7739
21
(MedDRA:10007697) Carpal tunnel syndrome Frequent [IBIS] 47% (n=32) 19781421 IBIS 16 / 7739
22
(HPO:0000802) Impotence 25819286 IBIS 20 / 7739
23
(HPO:0003458) EMG: myopathic abnormalities 25819286 IBIS 38 / 7739
24
(HPO:0001324) Muscle weakness 25819286 IBIS 859 / 7739
25
(HPO:0003401) Paresthesia 25819286 IBIS 42 / 7739
26
(HPO:0002019) Constipation 25819286 IBIS 194 / 7739
27
(HPO:0002014) Diarrhea 25819286 IBIS 225 / 7739
28
(HPO:0012722) Heart block 26610878 IBIS 5 / 7739
29
(MedDRA:10047240) Venous pressure jugular increased Frequent [IBIS] 69% (n=29) 19781421 IBIS 6 / 7739

Associated genes:

TTR;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
APOA1 rs28931575 pathogenic RCV000019524.27
APOA1 rs387906571 pathogenic RCV000019525.27
TTR rs104894664 pathogenic RCV000014379.23
TTR rs104894665 pathogenic RCV000014406.17
TTR rs104894665 pathogenic RCV000014403.24
TTR rs11541796 pathogenic RCV000014370.17
TTR rs121918068 pathogenic RCV000014398.24
TTR rs121918068 pathogenic RCV000014360.26
TTR rs121918069 pathogenic RCV000014377.24
TTR rs121918069 pathogenic RCV000014362.25
TTR rs121918070 pathogenic RCV000014363.28
TTR rs121918071 pathogenic RCV000014364.18
TTR rs121918072 pathogenic RCV000014365.26
TTR rs121918073 pathogenic RCV000014366.25
TTR rs121918075 pathogenic RCV000014361.23
TTR rs121918076 likely pathogenic RCV000030572.1
TTR rs121918076 pathogenic RCV000014371.25
TTR rs121918077 pathogenic RCV000014374.17
TTR rs121918079 pathogenic RCV000014380.17
TTR rs121918080 pathogenic RCV000014381.24
TTR rs121918081 pathogenic RCV000014383.18
TTR rs121918082 pathogenic RCV000014384.17
TTR rs121918083 pathogenic RCV000014386.26
TTR rs121918084 pathogenic RCV000014387.17
TTR rs121918085 pathogenic RCV000014388.25
TTR rs121918086 pathogenic RCV000014389.23
TTR rs121918087 pathogenic RCV000014390.24
TTR rs121918089 pathogenic RCV000014392.17
TTR rs121918090 pathogenic RCV000014393.24
TTR rs121918091 pathogenic RCV000014395.25
TTR rs121918093 pathogenic RCV000014397.23
TTR rs121918094 pathogenic RCV000014399.23
TTR rs121918095 pathogenic RCV000014400.25
TTR rs121918097 pathogenic RCV000014404.23
TTR rs121918098 pathogenic RCV000036373.2
TTR rs121918098 pathogenic RCV000014405.17
TTR rs121918100 pathogenic RCV000014408.23
TTR rs267607160 pathogenic RCV000014385.25
TTR rs267607161 pathogenic RCV000014410.24
TTR rs28933979 pathogenic RCV000014359.26
TTR rs28933979 pathogenic RCV000014382.25
TTR rs386134269 likely pathogenic RCV000030571.1
TTR rs387906523 pathogenic RCV000014378.25
TTR rs387906523 pathogenic RCV000014401.25
TTR rs76992529 pathogenic RCV000014368.21
TTR rs76992529 pathogenic RCV000030575.1
TTR rs79977247 pathogenic RCV000014372.25
TTR rs79977247 pathogenic RCV000014407.23

Additional Information:

Description: (OMIM) Hereditary amyloidoses are a clinically and genetically heterogeneous group of autosomal dominantly inherited diseases characterized by the deposit of unsoluble protein fibrils in the extracellular matrix (summary by Hund et al., 2001). Patients with transthyretin amyloidosis typically present ...
Clinical Description OMIM - Familial Amyloid Polyneuropathy

Familial amyloid polyneuropathy (FAP) was described by Andrade (1952) in the northern area of Portugal (reviewed by Saraiva, 2001). Kindreds had an age of onset of clinical symptoms in the third or ...

Molecular genetics OMIM The genetic defect in the kindreds from northern Portugal described by Andrade (1952) was heterozygosity for a valine-to-methionine substitution at residue 30 of transthyretin (V30M; 176300.0001) (Saraiva et al., 1984). Saraiva (2001) reported that over 500 kindreds had ...