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.
Dilated cardiomyopathy (DCM) is a heart muscle disease characterised by dilation and impaired contraction of the left or both ventricles that results in progressive heart failure and sudden cardiac death from ventricular arrhythmia. Genetically inherited forms of DCM ("familial" DCM) have been identified in 25-35% of patients presenting with this disease, and the inherited gene defects are an important cause of "familial" DCM. The pathophysiology may be separated into two categories: defects in force generation and defects in force transmission. In cases where an underlying pathology cannot be identified, the patient is diagnosed with an "idiopathic" DCM. Current hypotheses regarding causes of "idiopathic" DCM focus on myocarditis induced by enterovirus and subsequent autoimmune myocardium impairments. Antibodies to the beta1-adrenergic receptor (beta1AR), which are detected in a substantial number of patients with "idiopathic" DCM, may increase the concentration of intracellular cAMP and intracellular Ca2+, a condition often leading to a transient hyper-performance of the heart followed by depressed heart function and heart failure.
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
H00294 Dilated cardiomyopathy
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06528 Calcium signaling
H00294 Dilated cardiomyopathy
Cellular process
nt06539 Cytoskeleton in muscle cells
H00294 Dilated cardiomyopathy
Vatta M, Mohapatra B, Jimenez S, Sanchez X, Faulkner G, Perles Z, Sinagra G, Lin JH, Vu TM, Zhou Q, Bowles KR, Di Lenarda A, Schimmenti L, Fox M, Chrisco MA, Murphy RT, McKenna W, Elliott P, Bowles NE, Chen J, Valle G, Towbin JA
Title
Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction.
Hayashi T, Arimura T, Itoh-Satoh M, Ueda K, Hohda S, Inagaki N, Takahashi M, Hori H, Yasunami M, Nishi H, Koga Y, Nakamura H, Matsuzaki M, Choi BY, Bae SW, You CW, Han KH, Park JE, Knoll R, Hoshijima M, Chien KR, Kimura A
Title
Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy.
Carniel E, Taylor MR, Sinagra G, Di Lenarda A, Ku L, Fain PR, Boucek MM, Cavanaugh J, Miocic S, Slavov D, Graw SL, Feiger J, Zhu XZ, Dao D, Ferguson DA, Bristow MR, Mestroni L
Title
Alpha-myosin heavy chain: a sarcomeric gene associated with dilated and hypertrophic phenotypes of cardiomyopathy.
Norton N, Li D, Rieder MJ, Siegfried JD, Rampersaud E, Zuchner S, Mangos S, Gonzalez-Quintana J, Wang L, McGee S, Reiser J, Martin E, Nickerson DA, Hershberger RE
Title
Genome-wide studies of copy number variation and exome sequencing identify rare variants in BAG3 as a cause of dilated cardiomyopathy.
Ganapathi M, Argyriou L, Martinez-Azorin F, Morlot S, Yigit G, Lee TM, Auber B, von Gise A, Petrey DS, Thiele H, Cyganek L, Sabater-Molina M, Ahimaz P, Cabezas-Herrera J, Sorli-Garcia M, Zibat A, Siegelin MD, Burfeind P, Buchovecky CM, Hasenfuss G, Honig B, Li Y, Iglesias AD, Wollnik B
Title
Bi-allelic missense disease-causing variants in RPL3L associate neonatal dilated cardiomyopathy with muscle-specific ribosome biogenesis.
Jones EG, Mazaheri N, Maroofian R, Zamani M, Seifi T, Sedaghat A, Shariati G, Jamshidi Y, Allen HD, Wehrens XHT, Galehdari H, Landstrom AP
Title
Analysis of enriched rare variants in JPH2-encoded junctophilin-2 among Greater Middle Eastern individuals reveals a novel homozygous variant associated with neonatal dilated cardiomyopathy.
Hakui H, Kioka H, Miyashita Y, Nishimura S, Matsuoka K, Kato H, Tsukamoto O, Kuramoto Y, Takuwa A, Takahashi Y, Saito S, Ohta K, Asanuma H, Fu HY, Shinomiya H, Yamada N, Ohtani T, Sawa Y, Kitakaze M, Takashima S, Sakata Y, Asano Y
Title
Loss-of-function mutations in the co-chaperone protein BAG5 cause dilated cardiomyopathy requiring heart transplantation.
Verhagen JMA, van den Born M, van der Linde HC, G J Nikkels P, Verdijk RM, Kivlen MH, van Unen LMA, Baas AF, Ter Heide H, van Osch-Gevers L, Hoogeveen-Westerveld M, Herkert JC, Bertoli-Avella AM, van Slegtenhorst MA, Wessels MW, Verheijen FW, Hassel D, Hofstra RMW, Hegde RS, van Hasselt PM, van Ham TJ, van de Laar IMBH
Title
Biallelic Variants in ASNA1, Encoding a Cytosolic Targeting Factor of Tail-Anchored Proteins, Cause Rapidly Progressive Pediatric Cardiomyopathy.
Familial partial lipodystrophy (FPL) is a rare autosomal dominant disorder characterized by variable loss of body fat from the extremities as well as from the truncal region. LMNA, PPARG and AKT2 have been identified in association with FPL. However, it is not yet known how these genes cause the disorder. Besides them, additional loci are likely as many FPL patients do not reveal any mutations in these genes. LMNA mutations may affect nuclear function, and may be involved in apoptosis and premature cell death of adipocytes, thus causing lipodystrophy. PPARG, PLIN1, and AKT2 are regulators of adipocyte differentiation. AKT2 is also involved in postreceptor insulin signaling. Thus, mutations in these three genes could result in lipodystrophy. The reason why loss of fat is restricted to partial areas remains unknown. Recently, novel autosomal recessive causes of partial lipodystrophy were reported.
Category
Inherited metabolic disorder
Brite
Human diseases in ICD-11 classification [BR:br08403]
05 Endocrine, nutritional or metabolic diseases
Endocrine diseases
Other disorders of glucose regulation or pancreatic internal secretion
5A44 Insulin-resistance syndromes
H00420 Familial partial lipodystrophy
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06539 Cytoskeleton in muscle cells
H00420 Familial partial lipodystrophy
Gandotra S, Le Dour C, Bottomley W, Cervera P, Giral P, Reznik Y, Charpentier G, Auclair M, Delepine M, Barroso I, Semple RK, Lathrop M, Lascols O, Capeau J, O'Rahilly S, Magre J, Savage DB, Vigouroux C
Title
Perilipin deficiency and autosomal dominant partial lipodystrophy.
Schuermans N, El Chehadeh S, Hemelsoet D, Gautheron J, Vantyghem MC, Nouioua S, Tazir M, Vigouroux C, Auclair M, Bogaert E, Dufour S, Okawa F, Hilbert P, Van Doninck N, Taquet MC, Rosseel T, De Clercq G, Debackere E, Van Haverbeke C, Cherif FR, Urtizberea JA, Chanson JB, Funalot B, Authier FJ, Kaya S, Terryn W, Callens S, Depypere B, Van Dorpe J, Poppe B, Impens F, Mizushima N, Depienne C, Jeru I, Dermaut B
Title
Loss of phospholipase PLAAT3 causes a mixed lipodystrophic and neurological syndrome due to impaired PPARgamma signaling.
Semple RK, Sleigh A, Murgatroyd PR, Adams CA, Bluck L, Jackson S, Vottero A, Kanabar D, Charlton-Menys V, Durrington P, Soos MA, Carpenter TA, Lomas DJ, Cochran EK, Gorden P, O'Rahilly S, Savage DB
Title
Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis.
Charcot-Marie-Tooth (CMT) disease, also called hereditary motor and sensory neuropathy (HMSN), is a group of disorders characterized by a chronic motor and sensory polyneuropathy. Based on nerve conduction velocities, the disease can be divided into demyelinating CMT (CMT1), axonal CMT (CMT2) and intermediate CMT (CMTDI/CMTRI). Although more than 70 disease genes for CMT are known, a large number of affected individuals remain without a genetic diagnosis.
Category
Neurodegenerative disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
08 Diseases of the nervous system
Disorders of nerve root, plexus or peripheral nerves
Hereditary neuropathy
8C20 Hereditary motor and sensory neuropathy
H00264 Charcot-Marie-Tooth disease
Pathway-based classification of diseases [BR:br08402]
Replication and repair
nt06509 DNA replication
H00264 Charcot-Marie-Tooth disease
Cellular process
nt06515 Regulation of kinetochore-microtubule interactions
H00264 Charcot-Marie-Tooth disease
nt06532 Autophagy
H00264 Charcot-Marie-Tooth disease
nt06536 Mitophagy
H00264 Charcot-Marie-Tooth disease
nt06539 Cytoskeleton in muscle cells
H00264 Charcot-Marie-Tooth disease
CMT1: Abnormal myelin, autosomal dominant
CMT2: Axonopathy, autosomal dominant
Intermediate form: Combination of myelinopathy and axonopathy in individual, autosomal dominant
CMT4: Either myelinopathy or axonopathy, autosomal recessive
CMTX: Axonopathy with secondary myelin changes, X-linked dominant
MNMN: Mononeuropathy of the median nerve mild
Rebelo AP, Cortese A, Abraham A, Eshed-Eisenbach Y, Shner G, Vainshtein A, Buglo E, Camarena V, Gaidosh G, Shiekhattar R, Abreu L, Courel S, Burns DK, Bai Y, Bacon C, Feely SME, Castro D, Peles E, Reilly MM, Shy ME, Zuchner S
Title
A CADM3 variant causes Charcot-Marie-Tooth disease with marked upper limb involvement.
Guernsey DL, Jiang H, Bedard K, Evans SC, Ferguson M, Matsuoka M, Macgillivray C, Nightingale M, Perry S, Rideout AL, Orr A, Ludman M, Skidmore DL, Benstead T, Samuels ME
Title
Mutation in the gene encoding ubiquitin ligase LRSAM1 in patients with Charcot-Marie-Tooth disease.
Cottenie E, Kochanski A, Jordanova A, Bansagi B, Zimon M, Horga A, Jaunmuktane Z, Saveri P, Rasic VM, Baets J, Bartsakoulia M, Ploski R, Teterycz P, Nikolic M, Quinlivan R, Laura M, Sweeney MG, Taroni F, Lunn MP, Moroni I, Gonzalez M, Hanna MG, Bettencourt C, Chabrol E, Franke A, von Au K, Schilhabel M, Kabzinska D, Hausmanowa-Petrusewicz I, Brandner S, Lim SC, Song H, Choi BO, Horvath R, Chung KW, Zuchner S, Pareyson D, Harms M, Reilly MM, Houlden H
Title
Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2.
Higuchi Y, Hashiguchi A, Yuan J, Yoshimura A, Mitsui J, Ishiura H, Tanaka M, Ishihara S, Tanabe H, Nozuma S, Okamoto Y, Matsuura E, Ohkubo R, Inamizu S, Shiraishi W, Yamasaki R, Ohyagi Y, Kira J, Oya Y, Yabe H, Nishikawa N, Tobisawa S, Matsuda N, Masuda M, Kugimoto C, Fukushima K, Yano S, Yoshimura J, Doi K, Nakagawa M, Morishita S, Tsuji S, Takashima H
Title
Mutations in MME cause an autosomal-recessive Charcot-Marie-Tooth disease type 2.
Chelban V, Wilson MP, Warman Chardon J, Vandrovcova J, Zanetti MN, Zamba-Papanicolaou E, Efthymiou S, Pope S, Conte MR, Abis G, Liu YT, Tribollet E, Haridy NA, Botia JA, Ryten M, Nicolaou P, Minaidou A, Christodoulou K, Kernohan KD, Eaton A, Osmond M, Ito Y, Bourque P, Jepson JEC, Bello O, Bremner F, Cordivari C, Reilly MM, Foiani M, Heslegrave A, Zetterberg H, Heales SJR, Wood NW, Rothman JE, Boycott KM, Mills PB, Clayton PT, Houlden H
Title
PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation.
Kennerson ML, Yiu EM, Chuang DT, Kidambi A, Tso SC, Ly C, Chaudhry R, Drew AP, Rance G, Delatycki MB, Zuchner S, Ryan MM, Nicholson GA
Title
A new locus for X-linked dominant Charcot-Marie-Tooth disease (CMTX6) is caused by mutations in the pyruvate dehydrogenase kinase isoenzyme 3 (PDK3) gene.
Azzedine H, Zavadakova P, Plante-Bordeneuve V, Vaz Pato M, Pinto N, Bartesaghi L, Zenker J, Poirot O, Bernard-Marissal N, Arnaud Gouttenoire E, Cartoni R, Title A, Venturini G, Medard JJ, Makowski E, Schols L, Claeys KG, Stendel C, Roos A, Weis J, Dubourg O, Leal Loureiro J, Stevanin G, Said G, Amato A, Baraban J, LeGuern E, Senderek J, Rivolta C, Chrast R
Title
PLEKHG5 deficiency leads to an intermediate form of autosomal-recessive Charcot-Marie-Tooth disease.
Tamiya G, Makino S, Hayashi M, Abe A, Numakura C, Ueki M, Tanaka A, Ito C, Toshimori K, Ogawa N, Terashima T, Maegawa H, Yanagisawa D, Tooyama I, Tada M, Onodera O, Hayasaka K
Title
A mutation of COX6A1 causes a recessive axonal or mixed form of Charcot-Marie-Tooth disease.
Auer-Grumbach M, Weger M, Fink-Puches R, Papic L, Frohlich E, Auer-Grumbach P, El Shabrawi-Caelen L, Schabhuttl M, Windpassinger C, Senderek J, Budka H, Trajanoski S, Janecke AR, Haas A, Metze D, Pieber TR, Guelly C
Title
Fibulin-5 mutations link inherited neuropathies, age-related macular degeneration and hyperelastic skin.
Djordjevic D, Pinard M, Gauthier MS, Smith-Hicks C, Hoffman TL, Wolf NI, Oegema R, van Binsbergen E, Baskin B, Bernard G, Fribourg S, Coulombe B, Yoon G
Title
De novo variants in POLR3B cause ataxia, spasticity, and demyelinating neuropathy.
Montecchiani C, Pedace L, Lo Giudice T, Casella A, Mearini M, Gaudiello F, Pedroso JL, Terracciano C, Caltagirone C, Massa R, St George-Hyslop PH, Barsottini OG, Kawarai T, Orlacchio A
Title
ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease.
Collagen VI related myopathies [DS:H01341] Merosin-deficient CMD (MDC1A) [DS:H01958] Muscular dystrophy-dystroglycanopathy type A [DS:H00120] Muscular dystrophy-dystroglycanopathy type B [DS:H01960] Muscular dystrophy-dystroglycanopathy type C [DS:H01959] Rigid spine syndrome (RSS) [DS:H01310] Integrin alpha7-deficient CMD LMNA-deficient CMD CMD with hyperlaxity (CMDH) CMD Davignon-Chauveau type (MDCDC) CMD megaconial type (MDCMC) CMD with cataracts and intellectual disability (MDCCAID)
Description
Congenital muscular dystrophies (CMDs) are a heterogeneous group of inherited disorders characterized by muscle weakness from birth and variable clinical manifestations of the eye and central nervous system. According to the disease mechanisms, the CMDs may be grouped as follows: defects in genes encoding for structural proteins of the basal membrane or extracellular matrix of the skeletal muscle fibers, which include collagen 6 genes, laminin alpha2 chain and integrin alpha7; defects in genes encoding for putative or demonstrated glycosyltransferases, which include POMT1, POMT2, POMGnT1, fukutin, fukutin-related protein (FKRP), Large, and ISPD; defects in ER and nuclear proteins, which are selenoprotein 1 and lamin A/C.
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
H00590 Congenital muscular dystrophies (CMD/MDC)
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06539 Cytoskeleton in muscle cells
H00590 Congenital muscular dystrophies (CMD/MDC)
Collagen VI related myopathies [DS:H01341] includes Ullrich CMD (UCMD).
Muscular dystrophy-dystroglycanopathy type A [DS:H00120] includes Walker-Warburg syndrome (WWS), Muscle-eye-brain disease (MEB), and Fukuyama CMD (FCMD).
Muscular dystrophy-dystroglycanopathy type B [DS:H01960] includes MDC1C and MDC1D.
Kang PB, Morrison L, Iannaccone ST, Graham RJ, Bonnemann CG, Rutkowski A, Hornyak J, Wang CH, North K, Oskoui M, Getchius TS, Cox JA, Hagen EE, Gronseth G, Griggs RC
Title
Evidence-based guideline summary: evaluation, diagnosis, and management of congenital muscular dystrophy: Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Issues Review Panel of the American Association of Neuromuscular & Electrodiagnostic Medicine.
Hayashi YK, Chou FL, Engvall E, Ogawa M, Matsuda C, Hirabayashi S, Yokochi K, Ziober BL, Kramer RH, Kaufman SJ, Ozawa E, Goto Y, Nonaka I, Tsukahara T, Wang JZ, Hoffman EP, Arahata K
Title
Mutations in the integrin alpha7 gene cause congenital myopathy.
Hutchinson-Gilford progeria syndrome (HGPS) is a rare hereditary disorder characterized by premature aging. Children born with HGPS begin to develop micrognathia, alopecia, prominent scalp vein, and wrinkled, aged-looking skin within the first year of life. Severe premature atherosclerosis can cause the death at an average age of 13.5 years. Mutations in lamin A/C, an important structural component of the nuclear envelope, have been reported.
Category
Inherited metabolic disorder
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Multiple developmental anomalies or syndromes
LD2B Syndromes with premature ageing appearance as a major feature
H00601 Hutchinson-Gilford progeria syndrome
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06539 Cytoskeleton in muscle cells
H00601 Hutchinson-Gilford progeria syndrome
Restrictive dermopathy (RD) is a rare, lethal autosomal recessive genodermatosis caused by mutations in either LMNA or ZMPSTE24. Manifestations include a tight, thin, translucent skin, typical face, multiple joint contractures, enlarged fontanelles, and dysplasia of clavicles.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
14 Diseases of the skin
Skin disorders involving specific cutaneous structures
Disorders of the dermis and subcutis
Disorders of cutaneous connective tissue
Fibromatoses and keloids
EE6Y Other specified fibromatous disorders of skin and soft tissue
H00663 Restrictive dermopathy
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06539 Cytoskeleton in muscle cells
H00663 Restrictive dermopathy
Navarro CL, De Sandre-Giovannoli A, Bernard R, Boccaccio I, Boyer A, Genevieve D, Hadj-Rabia S, Gaudy-Marqueste C, Smitt HS, Vabres P, Faivre L, Verloes A, Van Essen T, Flori E, Hennekam R, Beemer FA, Laurent N, Le Merrer M, Cau P, Levy N
Title
Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy.
Mandibuloacral dysplasia (MAD) is an autosomal recessive disorder characterized by postnatal growth retardation, hypoplasia of the mandible and clavicles, acro-osteolysis, and partial lipodystrophy. Affected individuals have a normal appearance at birth, then progressively develop dysmorphic skeletal features. Mutations in LMNA or ZMPSTE24 are responsible for the disorder. Recently, a novel MAD progeroid syndrome due to recessive mutations in MTX2 has been reported. MTX2 encodes an outer mitochondrial membrane protein.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Multiple developmental anomalies or syndromes
LD27 Syndromes with skin or mucosal anomalies as a major feature
H00665 Mandibuloacral dysplasia
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06539 Cytoskeleton in muscle cells
H00665 Mandibuloacral dysplasia
Elouej S, Harhouri K, Le Mao M, Baujat G, Nampoothiri S, Kayserili H, Menabawy NA, Selim L, Paneque AL, Kubisch C, Lessel D, Rubinsztajn R, Charar C, Bartoli C, Airault C, Deleuze JF, Rotig A, Bauer P, Pereira C, Loh A, Escande-Beillard N, Muchir A, Martino L, Gruenbaum Y, Lee SH, Manivet P, Lenaers G, Reversade B, Levy N, De Sandre-Giovannoli A
Title
Loss of MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology.
Holt-Oram syndrome [DS:H00433] Berk-Tabatznik syndrome Heart-hand syndrome, Slovenian type Long thumb brachydactyly syndrome
Description
Heart-hand syndrome (HHS) is a clinically and genetically heterogeneous disorder characterized by the co-occurrence of a congenital cardiac disease and limb malformations. HHS includes the most common type HHS of Holt-Oram syndrome (HOS) and several rare types. TBX5 and LMNA are the only two genes found to contribute to HHS, causing HOS and HHS Slovenian type (HHS-S), respectively.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Multiple developmental anomalies or syndromes
LD2F Syndromes with multiple structural anomalies, without predominant body system involvement
H02725 Heart-hand syndrome
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06539 Cytoskeleton in muscle cells
H02725 Heart-hand syndrome
