DISEASE: Arrhythmogenic right ventricular cardiomyopathy
Entry
H00293 Disease
Name
Arrhythmogenic right ventricular cardiomyopathy
Description
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are progressive myocyte loss and fibrofatty replacement, with a predilection for the right ventricle. A number of genetic studies have identified mutations in various components of the cardiac desmosome that have important roles in the pathogenesis of ARVC. Disruption of desmosomal function by defective proteins might lead to death of myocytes under mechanical stress. The myocardial injury may be accompanied by inflammation. Since regeneration of cardiac myocytes is limited, repair by fibrofatty replacement occurs. Several studies have implicated that desmosome dysfunction results in the delocalization and nuclear translocation of plakoglobin. As a result, competition between plakoglobin and beta-catenin will lead to the inhibition of Wnt/beta-catenin signaling, resulting in a shift from a myocyte fate towards an adipocyte fate of cells. The ryanodine receptor plays a crucial part in electromechanical coupling by control of release of calcium from the sarcoplasmic reticulum into the cytosol. Therefore, defects in this receptor could result in an imbalance of calcium homeostasis that might trigger cell death.
Category
Cardiovascular disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
11 Diseases of the circulatory system
Diseases of the myocardium or cardiac chambers
BC43 Cardiomyopathy
H00293 Arrhythmogenic right ventricular cardiomyopathy
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06528 Calcium signaling
H00293 Arrhythmogenic right ventricular cardiomyopathy
Cellular process
nt06539 Cytoskeleton in muscle cells
H00293 Arrhythmogenic right ventricular cardiomyopathy
Tiso N, Stephan DA, Nava A, Bagattin A, Devaney JM, Stanchi F, Larderet G, Brahmbhatt B, Brown K, Bauce B, Muriago M, Basso C, Thiene G, Danieli GA, Rampazzo A
Title
Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2).
Merner ND, Hodgkinson KA, Haywood AF, Connors S, French VM, Drenckhahn JD, Kupprion C, Ramadanova K, Thierfelder L, McKenna W, Gallagher B, Morris-Larkin L, Bassett AS, Parfrey PS, Young TL
Title
Arrhythmogenic right ventricular cardiomyopathy type 5 is a fully penetrant, lethal arrhythmic disorder caused by a missense mutation in the TMEM43 gene.
van Hengel J, Calore M, Bauce B, Dazzo E, Mazzotti E, De Bortoli M, Lorenzon A, Li Mura IE, Beffagna G, Rigato I, Vleeschouwers M, Tyberghein K, Hulpiau P, van Hamme E, Zaglia T, Corrado D, Basso C, Thiene G, Daliento L, Nava A, van Roy F, Rampazzo A
Title
Mutations in the area composita protein alphaT-catenin are associated with arrhythmogenic right ventricular cardiomyopathy.
Mayosi BM, Fish M, Shaboodien G, Mastantuono E, Kraus S, Wieland T, Kotta MC, Chin A, Laing N, Ntusi NB, Chong M, Horsfall C, Pimstone SN, Gentilini D, Parati G, Strom TM, Meitinger T, Pare G, Schwartz PJ, Crotti L
Title
Identification of Cadherin 2 (CDH2) Mutations in Arrhythmogenic Right Ventricular Cardiomyopathy.
Emery-Dreifuss muscular dystrophy (EDMD) is characterized by the clinical triad of joint contractures that begin in early childhood, slowly progressive muscle weakness and wasting initially in a humeroperoneal distribution that later extends to the scapular and pelvic girdle muscles, and cardiac involvement that usually occurs after the second decade of life. So far, five genes, EMD (emerin), LMNA, SYNE (nesprin)1, SYNE2 and FHL1, have been associated to EDMD phenotypes, that can be inherited following an X-linked, autosomal dominant or autosomal recessive pattern of inheritance. Most of genes known to be associated with EDMD are critical for nuclear envelope integrity.
Category
Nervous system disease; Musculoskeletal disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
08 Diseases of the nervous system
Diseases of neuromuscular junction or muscle
Primary disorders of muscles
8C70 Muscular dystrophy
H00563 Emery-Dreifuss muscular dystrophy
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06539 Cytoskeleton in muscle cells
H00563 Emery-Dreifuss muscular dystrophy
Raffaele Di Barletta M, Ricci E, Galluzzi G, Tonali P, Mora M, Morandi L, Romorini A, Voit T, Orstavik KH, Merlini L, Trevisan C, Biancalana V, Housmanowa-Petrusewicz I, Bione S, Ricotti R, Schwartz K, Bonne G, Toniolo D
Title
Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy.
Zhang Q, Bethmann C, Worth NF, Davies JD, Wasner C, Feuer A, Ragnauth CD, Yi Q, Mellad JA, Warren DT, Wheeler MA, Ellis JA, Skepper JN, Vorgerd M, Schlotter-Weigel B, Weissberg PL, Roberts RG, Wehnert M, Shanahan CM
Title
Nesprin-1 and -2 are involved in the pathogenesis of Emery Dreifuss muscular dystrophy and are critical for nuclear envelope integrity.
Auditory neuropathy is a rare form of deafness characterized by an absent or abnormal auditory brainstem response with preservation of outer hair cell function. DIAPH3 has been identified as the gene responsible for autosomal dominant nonsyndromic auditory neuropathy. Recently, it has been reported that an autosomal recessive auditory neuropathy and optic atrophy (ANOA) is caused by mutations in the FDXR gene.
Category
Nervous system disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
10 Diseases of the ear or mastoid process
Disorders with hearing impairment
AB57 Auditory synaptopathy or neuropathy
H02339 Auditory neuropathy
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06535 Efferocytosis
H02339 Auditory neuropathy
nt06539 Cytoskeleton in muscle cells
H02339 Auditory neuropathy
Jang MW, Oh DY, Yi E, Liu X, Ling J, Kim N, Sharma K, Kim TY, Lee S, Kim AR, Kim MY, Kim MA, Lee M, Han JH, Han JJ, Park HR, Kim BJ, Lee SY, Woo DH, Oh J, Oh SJ, Du T, Koo JW, Oh SH, Shin HW, Seong MW, Lee KY, Kim UK, Shin JB, Sang S, Cai X, Mei L, He C, Blanton SH, Chen ZY, Chen H, Liu X, Nourbakhsh A, Huang Z, Kang KW, Park WY, Feng Y, Lee CJ, Choi BY
Title
A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder.
Paul A, Drecourt A, Petit F, Deguine DD, Vasnier C, Oufadem M, Masson C, Bonnet C, Masmoudi S, Mosnier I, Mahieu L, Bouccara D, Kaplan J, Challe G, Domange C, Mochel F, Sterkers O, Gerber S, Nitschke P, Bole-Feysot C, Jonard L, Gherbi S, Mercati O, Ben Aissa I, Lyonnet S, Rotig A, Delahodde A, Marlin S
Title
FDXR Mutations Cause Sensorial Neuropathies and Expand the Spectrum of Mitochondrial Fe-S-Synthesis Diseases.
