Juvenile myelomonocytic leukemia (JMML) is a rare clonal hematopoietic disorder of early childhood with features characteristic of both myelodysplastic and myeloproliferative disorders. Recent studies have shown that abnormal proliferation is due to aberrant signal transduction resulting from mutations in components of the RAS-signaling pathway.
Category
Cancer
Brite
Human diseases in ICD-11 classification [BR:br08403]
02 Neoplasms
Neoplasms of haematopoietic or lymphoid tissues
Myelodysplastic and myeloproliferative neoplasms
2A42 Juvenile myelomonocytic leukaemia
H02541 Juvenile myelomonocytic leukemia
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06526 MAPK signaling
H02541 Juvenile myelomonocytic leukemia
Cellular process
nt06546 IgSF CAM signaling
H02541 Juvenile myelomonocytic leukemia
Borkhardt A, Bojesen S, Haas OA, Fuchs U, Bartelheimer D, Loncarevic IF, Bohle RM, Harbott J, Repp R, Jaeger U, Viehmann S, Henn T, Korth P, Scharr D, Lampert F
Title
The human GRAF gene is fused to MLL in a unique t(5;11)(q31;q23) and both alleles are disrupted in three cases of myelodysplastic syndrome/acute myeloid leukemia with a deletion 5q.
Neurofibromatosis type 1 (NF1), also known as von Recklinghausen's disease, is an autosomal dominant disease caused by mutations of NF1 gene on chromosome 17. The NF1 gene encodes a RAS GTPase-activating protein called neurofibromin. It is one of the most frequent human genetic diseases, with a prevalence of one case in 3000 births and there is no sex or racial predilection. NF1 is characterized by multiple cafe-au-lait spots, axillary and inguinal freckling, multiple cutaneous neurofibromas, and iris Lisch nodules. Learning disabilities are present in at least 50% of individuals with NF1. Less common but potentially more serious manifestations include plexiform neurofibromas, optic nerve and other central nervous system gliomas, malignant peripheral nerve sheath tumors, scoliosis, tibial dysplasia, and vasculopathy.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Multiple developmental anomalies or syndromes
LD2D Phakomatoses or hamartoneoplastic syndromes
H01437 Neurofibromatosis type 1
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06526 MAPK signaling
H01437 Neurofibromatosis type 1
Paragangliomas (PGLs) are rare neuroendocrine tumors that arise in sympathetic and parasympathetic paraganglia and derive from neural crest cells. Malignancy is defined by presence of metastases, tumor spread in sites where chromaffin tissue is normally absent such as lymph nodes, liver, lungs, and bones. Malignant PGLs are extremely rare. The pathogenesis and progression of PGLs are very strongly influenced by genetics. A germline mutation in one of the susceptibility genes identified so far explains ~40% of all cases; the remaining 60% are thought to be sporadic cases. Sporadic as well as hereditary PGLs have been divided in two main clusters linked to two different signalling pathways: the first cluster contains all VHL-, SDHx-, and FH- mutated tumors and is associated to the activation of hypoxic pathway, while the second cluster contains all RET- , NF1-, MAX and TMEM127- mutated tumors and is associated to the activation of MAPK and mTOR (mammalian target of rapamycin) signaling pathways.
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 endocrine glands
2D12 Malignant neoplasms of other endocrine glands or related structures
H01510 Malignant paraganglioma
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06526 MAPK signaling
H01510 Malignant paraganglioma
Cellular process
nt06523 Epigenetic regulation by Polycomb complexes
H01510 Malignant paraganglioma
Noonan syndrome and related disorders [DS:H00523] Neurofibromatosis type 1 [DS:H01437]
Description
Neurofibromatosis-Noonan syndrome (NFNS) presents combined characteristics of both autosomal dominant disorders, neurofibromatosis type 1 (NF1) and Noonan syndrome (NS). NF1 is characterized by neurofibromas, cafe-au-lait spots, osseous lesions, and brain tumors such as gliomas. NS presents characteristic facial appearance, short stature, hypertelorism, strabismus, and low-set ears. It has been reported that mutations in the NF1 gene are associated with NFNS.
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
H02189 Neurofibromatosis-Noonan syndrome
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06526 MAPK signaling
H02189 Neurofibromatosis-Noonan syndrome
Watson syndrome (WTSN) is an autosomal dominant condition characterized by the presence of pulmonary valvular stenosis, cafe au lait spots, and mild mental retardation. These features are also sometimes observed in neurofibromatosis type 1 (NF1). It has been suggested that Watson syndrome is caused by mutations in NF1 gene.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
14 Diseases of the skin
Genetic and developmental disorders affecting the skin
EC23 Genetic disorders of skin pigmentation
H02188 Watson syndrome
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06526 MAPK signaling
H02188 Watson syndrome
