Dyskeratosis congenita (DC) is a severe inherited bone marrow failure syndrome with associated cutaneous and noncutaneous abnormalities. In most cases, the inheritance pattern is X-linked recessive, while autosomal dominant and autosomal recessive forms have been reported. Remarkably, all causative gene mutations identified to date share a link to telomere/telomerase biology. Moreover, dyskeratosis congenita is linked to defective ribosome biogenesis.
Category
Ribosomopathy
Brite
Human diseases in ICD-11 classification [BR:br08403]
03 Diseases of the blood or blood-forming organs
Anaemias or other erythrocyte disorders
3A70 Aplastic anaemia
H00507 Dyskeratosis congenita
Pathway-based classification of diseases [BR:br08402]
Replication and repair
nt06510 Telomere length regulation
H00507 Dyskeratosis congenita
nt06506 Double-strand break repair
H00507 Dyskeratosis congenita
Guo Y, Kartawinata M, Li J, Pickett HA, Teo J, Kilo T, Barbaro PM, Keating B, Chen Y, Tian L, Al-Odaib A, Reddel RR, Christodoulou J, Xu X, Hakonarson H, Bryan TM
Title
Inherited bone marrow failure associated with germline mutation of ACD, the gene encoding telomere protein TPP1.
Dhanraj S, Gunja SM, Deveau AP, Nissbeck M, Boonyawat B, Coombs AJ, Renieri A, Mucciolo M, Marozza A, Buoni S, Turner L, Li H, Jarrar A, Sabanayagam M, Kirby M, Shago M, Pinto D, Berman JN, Scherer SW, Virtanen A, Dror Y
Title
Bone marrow failure and developmental delay caused by mutations in poly(A)-specific ribonuclease (PARN).
Kermasson L, Churikov D, Awad A, Smoom R, Lainey E, Touzot F, Audebert-Bellanger S, Haro S, Roger L, Costa E, Mouf M, Bottero A, Oleastro M, Abdo C, de Villartay JP, Geli V, Tzfati Y, Callebaut I, Danielian S, Soares G, Kannengiesser C, Revy P
Title
Inherited human Apollo deficiency causes severe bone marrow failure and developmental defects.
Tummala H, Walne A, Buccafusca R, Alnajar J, Szabo A, Robinson P, McConkie-Rosell A, Wilson M, Crowley S, Kinsler V, Ewins AM, Madapura PM, Patel M, Pontikos N, Codd V, Vulliamy T, Dokal I
Pulmonary fibrosis and/or bone marrow failure, telomere-related (PFBMFT) is also known as human telomere biology disorders, or short telomere syndromes. PFBMFT is a group of hereditary disorders caused by inherited loss-of-function mutations in telomere associated genes. It has a wide phenotypic spectrum that include bone marrow failure, pulmonary and liver fibrosis, mucocutaneous fragility, and predisposition to myelodysplastic syndromes and cancer.
Category
Hematologic disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
03 Diseases of the blood or blood-forming organs
Anaemias or other erythrocyte disorders
3A70 Aplastic anaemia
H02569 Pulmonary fibrosis and/or bone marrow failure, telomere-related
Pathway-based classification of diseases [BR:br08402]
Replication and repair
nt06509 DNA replication
H02569 Pulmonary fibrosis and/or bone marrow failure, telomere-related
nt06510 Telomere length regulation
H02569 Pulmonary fibrosis and/or bone marrow failure, telomere-related
nt06502 Nucleotide excision repair
H02569 Pulmonary fibrosis and/or bone marrow failure, telomere-related
nt06506 Double-strand break repair
H02569 Pulmonary fibrosis and/or bone marrow failure, telomere-related
nt06508 Interstrand crosslink repair
H02569 Pulmonary fibrosis and/or bone marrow failure, telomere-related
Kelich J, Aramburu T, van der Vis JJ, Showe L, Kossenkov A, van der Smagt J, Massink M, Schoemaker A, Hennekam E, Veltkamp M, van Moorsel CHM, Skordalakes E
Title
Telomere dysfunction implicates POT1 in patients with idiopathic pulmonary fibrosis.
Kannengiesser C, Manali ED, Revy P, Callebaut I, Ba I, Borgel A, Oudin C, Haritou A, Kolilekas L, Malagari K, Borie R, Lainey E, Boileau C, Crestani B, Papiris SA
Title
First heterozygous NOP10 mutation in familial pulmonary fibrosis.
Aplastic anemia (AA) is a rare disease in which the reduction of the circulating blood cells results from damage to the stem cell pool in bone marrow. Most cases of acquired aplastic anemia are the consequence of an immune-mediated destruction of hematopoiesis. Autoreactive cytotoxic T cells play a key role in the pathogenesis of AA by myelosuppressive cytokines including interferon-gamma. It has been reported that polymorphisms in IFNG are related to AA. A minority of patients with AA has heterozygous mutations in genes encoding the telomerase components TERT or TERC. Immunosuppressive therapy (IST) is one of the main treatment modalities for AA, although most patients with telomerase mutations do not respond adequately to IST.
Category
Hematologic disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
03 Diseases of the blood or blood-forming organs
Anaemias or other erythrocyte disorders
3A70 Aplastic anaemia
H01132 Aplastic anemia
Pathway-based classification of diseases [BR:br08402]
Replication and repair
nt06510 Telomere length regulation
H01132 Aplastic anemia
nt06506 Double-strand break repair
H01132 Aplastic anemia
Melanoma is a form of skin cancer that has a poor prognosis and which is on the rise in Western populations. Melanoma arises from the malignant transformation of pigment-producing cells, melanocytes. The only known environmental risk factor is exposure to ultraviolet (UV) light and in people with fair skin the risk is greatly increased. Melanoma pathogenesis is also driven by genetic factors. Oncogenic NRAS mutations activate both effector pathways Raf-MEK-ERK and PI3K-Akt. The Raf-MEK-ERK pathway may also be activated via mutations in the BRAF gene. The PI3K-Akt pathway may be activated through loss or mutation of the inhibitory tumor suppressor gene PTEN. These mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression. Melanoma development has been shown to be strongly associated with inactivation of the p16INK4a/cyclin dependent kinases 4 and 6/retinoblastoma protein (p16INK4a/CDK4,6/pRb) and p14ARF/human double minute 2/p53 (p14ARF/HMD2/p53) tumor suppressor pathways. MITF and TP53 are implicated in further melanoma progression.
Category
Cancer
Brite
Human diseases in ICD-11 classification [BR:br08403]
02 Neoplasms
Malignant neoplasms, except primary neoplasms of lymphoid, haematopoietic, central nervous system or related tissues
Malignant neoplasms, stated or presumed to be primary, of specified sites, except of lymphoid, haematopoietic, central nervous system or related tissues
Malignant neoplasms of skin
2C30 Melanoma of skin
H00038 Melanoma
Pathway-based classification of diseases [BR:br08402]
Replication and repair
nt06510 Telomere length regulation
H00038 Melanoma
nt06506 Double-strand break repair
H00038 Melanoma
Signal transduction
nt06526 MAPK signaling
H00038 Melanoma
Tumor markers [br08442.html]
H00038
Cancer-associated carbohydrates [br08441.html]
H00038
Kannengiesser C, Dalle S, Leccia MT, Avril MF, Bonadona V, Chompret A, Lasset C, Leroux D, Thomas L, Lesueur F, Lenoir G, Sarasin A, Bressac-de Paillerets B
Title
New founder germline mutations of CDKN2A in melanoma-prone families and multiple primary melanoma development in a patient receiving levodopa treatment.