Monogenic hearing loss
Gene: KIT
Comment when marking as ready: Promoted to green after confirmation of the association with the reviewer.Created: 2 Mar 2016, 11:09 a.m.
Comment on list classification: Discussed with reviewer - the association of piebaldism and deafness is very well established.Created: 2 Mar 2016, 11:08 a.m.
Comment on mode of inheritance: From the 3 pulications reporting variants in patients.Created: 2 Mar 2016, 11:05 a.m.
Seems to be a clear association between mutations in this gene and piebaldism. PMID: 9450866 - reports a novel missense substitution in KIT (heterozygous) in a South African girl with severe piebaldism and profound congenital sensorineural deafness. PMID: 15099345 - a report of a 21-year old woman with congenital sensorineural hearing loss (without pigmentary abnormalities) who had the same KIT mutation as her mother with piebaldism, as well as two mutations in the SLC26A4 gene. Her hearing loss was attributed to mutations in the SLC26A4 gene, and non-penetrance of piebaldism. PMID: 23399981 - A report of a proband with no pigmentation of his skin nor hair and blue irides, and pro- found sensorineural hearing loss. A homozygous deletion of exons 20 and 21 in the proband was found, and parents were heterozygous for these deletions (homozygosity for piebaldism is clinically more severe than heterozygous state). Also describe other published studies of c-kit mutations in mice, which have defects including albinism and deafness.Created: 2 Mar 2016, 11:03 a.m.
Inheritance:Autosomal dominant;Isolated cases;Somatic mutationCreated: 9 Feb 2016, 10:07 a.m.
Inheritance:Autosomal dominant;Somatic mutation;Isolated casesCreated: 7 Feb 2016, 4:53 p.m.
Inheritance:Autosomal dominant;Isolated cases;Somatic mutationCreated: 7 Feb 2016, 3:43 p.m.
Inheritance:Autosomal dominant,Isolated cases,Somatic mutationCreated: 7 Feb 2016, 9:26 a.m.
Inheritance:Somatic mutationCreated: 7 Feb 2016, 8:58 a.m.
Mode of inheritance
Other
Phenotypes
#154800:Mast cell disease[Hyperpigmented macules or papules showing erythema or edema on trauma; Urticaria pigmentosa; Cutaneous mastocytosis; Bullous mastocytosis; Telangiectasia macularis eruptiva perstans; Systemic mastocytosis may affect bone, GI tract, lymphatics, spleen, and liver]; #172800:Piebaldism[Piebaldism; White forelock; Absent pigmentation of medial forehead, eyebrows and chin; Absent pigmentation of ventral chest, abdomen and limbs; Hyperpigmented borders of unpigmented areas; Heterochromia iridis; Frequent epitheliomas; Occasional deafness; Rare Hirschsprung disease]; #273300:Germ cell tumors[Painless testicular mass; Male germ cell tumors (GCT), 2 subtypes -SeminomaNonseminoma (embryonal carcinoma, teratoma, choriocarcinoma, endodermal sinus tumor); Isochromosome 12p (i(12p))Elevated hCG (choriocarcinoma)Elevated AFP (endodermal sinus tumor)Elevated hCG or AFP or both (embryonal carcinoma)Azoospermia/oligospermia (present at diagnosis)]; #601626:Leukemia, acute myeloid[Familial acute myelogenous leukemia (AML); Evidence of anticipation; Mean onset age 57 years, 32 years and 13 years in successive generations]; #606764:Gastrointestinal stromal tumor, familial[Gastrointestinal stromal tumorsPathology resembles neurofibromasHyperplasia of the myenteric plexusIntestinal obstructionConstipation (reported in 1 family with a PDFGRA mutation)Dysphagia; Large hands (in patients with PDGFRA mutations); Hyperpigmentation (in patients with KIT mutations)Urticaria pigmentosa or cutaneous mastocytosis (in patients with KIT mutations)]
Publications
Comment on list classification: Not sure of source of evidence for hearing loss?Created: 1 Feb 2016, 4:59 p.m.
Phenotypes for KIT were set to Piebaldism and congenital sensorineural hearing loss
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Publications for KIT were set to PMID: 23399981; 15099345; 9450866; 10362788; 10589513; 10620616; 10655061; 10716931; 11073817; 11074500; 11174389; 11287975; 11380399; 11493470; 11505412; 11870247; 12140361; 12420135; 12754375; 12773427; 1279971; 1370874; 1376329; 1377810; 1384325; 15824741; 16061643; 16724059; 1688471; 1693331; 1711207; 1717985; 1720553; 17420286; 18239612; 1826051; 19643989; 20927104; 2448137; 2457811; 2458842; 3049687; 3360448; 7479840; 7513208; 7530333; 7691885; 8579844; 8589724; 8875890; 9029028; 9438854; 9450866; 9657776; 9662380; 9697690; 9699740; 9724328; 9778516; 9827716; 9916918; 9990072
Mode of inheritance for KIT was changed to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for KIT were set to Piebaldism
Publications for KIT were set to PMID:10362788; 10589513; 10620616; 10655061; 10716931; 11073817; 11074500; 11174389; 11287975; 11380399; 11493470; 11505412; 11870247; 12140361; 12420135; 12754375; 12773427; 1279971; 1370874; 1376329; 1377810; 1384325; 15824741; 16061643; 16724059; 1688471; 1693331; 1711207; 1717985; 1720553; 17420286; 18239612; 1826051; 19643989; 20927104; 2448137; 2457811; 2458842; 3049687; 3360448; 7479840; 7513208; 7530333; 7691885; 8579844; 8589724; 8875890; 9029028; 9438854; 9450866; 9657776; 9662380; 9697690; 9699740; 9724328; 9778516; 9827716; 9916918; 9990072
This gene has been classified as Red List (Low Evidence).
This gene has been classified as Red List (Low Evidence).
KIT was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Expert
KIT was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Expert