Activity
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| Autoinflammatory disorders v2.32 | ITCH |
Achchuthan Shanmugasundram Tag Q3_25_promote_green tag was added to gene: ITCH. Tag Q3_25_NHS_review tag was added to gene: ITCH. |
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| Autoinflammatory disorders v2.32 | ITCH | Achchuthan Shanmugasundram Phenotypes for gene: ITCH were changed from Autoimmune disease, multisystem, with facial dysmorphism, 613385 to Autoimmune disease, multisystem, with facial dysmorphism, OMIM:613385; syndromic multisystem autoimmune disease due to ITCH deficiency, MONDO:0013245 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Autoinflammatory disorders v2.31 | ITCH | Achchuthan Shanmugasundram Publications for gene: ITCH were set to PMID: 36338154 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Autoinflammatory disorders v2.30 | ITCH | Achchuthan Shanmugasundram Classified gene: ITCH as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Autoinflammatory disorders v2.30 | ITCH | Achchuthan Shanmugasundram Gene: itch has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Autoinflammatory disorders v2.29 | ITCH | Ida Ertmanska edited their review of gene: ITCH: Changed publications to: 18727493, 20170897, 30705142, 31091003, 33894394, 36338154 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Autoinflammatory disorders v2.29 | ITCH | Ida Ertmanska edited their review of gene: ITCH: Changed phenotypes to: Autoimmune disease, multisystem, with facial dysmorphism, OMIM:613385, syndromic multisystem autoimmune disease due to ITCH deficiency, MONDO:0013245 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Autoinflammatory disorders v2.29 | ITCH | Ida Ertmanska edited their review of gene: ITCH: Changed publications to: 20170897, 30705142, 31091003, 33894394, 36338154 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Autoinflammatory disorders v2.29 | ITCH |
Ida Ertmanska changed review comment from: As reviewed by Nicholas Head, this gene is already Green on the Primary immunodeficiency or monogenic inflammatory bowel disease panel. ITCH is associated with AR Autoimmune disease, multisystem, with facial dysmorphism, OMIM:613385 (accessed 10th Oct 2025). PMID: 36338154 Wolfe et al., 2022 20yo non-consanguineous Caucasian female with novel ITCH variants: c.599dupC; p.(Ser201Ilefs*8) & deletion of exons 24 and 25. Phenotype: dysmorphic facial features, autoimmune disease including polymyositis, enteropathy, arthritis, psoriasis, hepatitis, and respiratory insufficiency; history of multiple hospitalizations for infections. Muscle biopsy showed 57% of expected mitochondrial DNA copy number but no change in the mitochondrial morphology. Demonstrated mitochondrial energy dysfunction in patient derived ITCH deficient fibroblasts, including reduced oxygen consumption (OCR) and a decrease in cellular ATP production. PMID: 33894394 Patel et al., 2022 Male patient compound heterozygous NM_001257137(ITCH): (c.337+2T>C) and (c.772C>T; p.Arg258*). Method: WES. Phenotype: multi-system immune dysregulation presenting with growth failure, very early onset inflammatory bowel disease (VEO-IBD), arthritis, uveitis, psoriasis and type 1 diabetes mellitus. Reported reduced expression of ITCH mRNA and absent ITCH protein. Immune dysregulation was successfully treated with hematopoietic cell transplantation. PMID: 31091003 Brittain et al, 2019 Report of a 23 yo female with biallelic truncating variants ITCH: paternally inherited c.726del; p.(Leu243SerfsTer63) and maternally inherited c.2125_2128del; p.(Glu710PhefsTer2) - neither variant found in gnomAD v4. No known consanguinity. Method: Trio Exome. Phenotype: marked short stature, severe early onset chronic lung disease resembling asthma, dysmorphic facial features, and symmetrical camptodactyly of the fingers but normal intellect. PMID: 30705142 Kleine-Eggebrecht et al., 2019 1-year-old girl of consanguineous parents with a homozygous mutation in ITCH: c.1570-1G > A. Method: trio WES. Phenotype: dystrophy, short stature, psychomotor retardation, and muscular hypotonia, as well as multisystemic autoimmune disease with detection of specific antibodies (de novo autoimmune hepatitis, thyroiditis with exophthalmos, diabetes mellitus type 1, and immune neutropenia). PMID: 20170897 Lohr et al., 2010 Described 10 Amish patients from 8 consanguineous and related families with multisystem autoimmune disease with delayed gross motor and cognitive skills, and facial dysmorphism. 6 of the children had evidence of autoimmune disease, including hypothyroidism in four, autoimmune hepatitis in three, autoimmune enteropathy with chronic diarrhea in two, and one had diabetes. All individuals were homozygous for the variant NM_031483.6(ITCH): c.394dupA p.(Ile132Asnfs) - founder effect. Functional evidence: PMID: 18727493 Matesic et al. 2008 itch−/− mice develop an autoimmune-like disease characterized histologically by a mixed infiltrate in nearly every organ system, lymphoproliferation resulting in splenomegaly and lymphadenopathy, and cortical atrophy of the thymus; the KO mice also produce antinuclear antibodies.; to: As reviewed by Nicholas Head, this gene is already Green on the Primary immunodeficiency or monogenic inflammatory bowel disease panel. ITCH is associated with AR Autoimmune disease, multisystem, with facial dysmorphism, OMIM:613385 (accessed 10th Oct 2025). PMID: 36338154 Wolfe et al., 2022 20yo non-consanguineous Caucasian female with novel ITCH variants: c.599dupC; p.(Ser201Ilefs*8) & deletion of exons 24 and 25. Phenotype: dysmorphic facial features, autoimmune disease including polymyositis, enteropathy, arthritis, psoriasis, hepatitis, and respiratory insufficiency; history of multiple hospitalizations for infections. Muscle biopsy showed 57% of expected mitochondrial DNA copy number but no change in the mitochondrial morphology. Demonstrated mitochondrial energy dysfunction in patient-derived ITCH-deficient fibroblasts, including reduced oxygen consumption (OCR) and a decrease in cellular ATP production. PMID: 33894394 Patel et al., 2022 Male patient compound heterozygous NM_001257137(ITCH): (c.337+2T>C) and (c.772C>T; p.Arg258*). Method: WES. Phenotype: multi-system immune dysregulation presenting with growth failure, very early onset inflammatory bowel disease (VEO-IBD), arthritis, uveitis, psoriasis and type 1 diabetes mellitus. Reported reduced expression of ITCH mRNA and absent ITCH protein. Immune dysregulation was successfully treated with hematopoietic cell transplantation. PMID: 31091003 Brittain et al, 2019 Report of a 23 yo female with biallelic truncating variants ITCH: paternally inherited c.726del; p.(Leu243SerfsTer63) and maternally inherited c.2125_2128del; p.(Glu710PhefsTer2) - neither variant found in gnomAD v4. No known consanguinity. Method: Trio Exome. Phenotype: marked short stature, severe early onset chronic lung disease resembling asthma, dysmorphic facial features, and symmetrical camptodactyly of the fingers but normal intellect. PMID: 30705142 Kleine-Eggebrecht et al., 2019 1-year-old girl of consanguineous parents with a homozygous mutation in ITCH: c.1570-1G > A. Method: trio WES. Phenotype: dystrophy, short stature, psychomotor retardation, and muscular hypotonia, as well as multisystemic autoimmune disease with detection of specific antibodies (de novo autoimmune hepatitis, thyroiditis with exophthalmos, diabetes mellitus type 1, and immune neutropenia). PMID: 20170897 Lohr et al., 2010 Described 10 Amish patients from 8 consanguineous and related families with multisystem autoimmune disease with delayed gross motor and cognitive skills, and facial dysmorphism. 6 of the children had evidence of autoimmune disease, including hypothyroidism in four, autoimmune hepatitis in three, autoimmune enteropathy with chronic diarrhea in two, and one had diabetes. All individuals were homozygous for the variant NM_031483.6(ITCH): c.394dupA p.(Ile132Asnfs) - founder effect. Functional evidence: PMID: 18727493 Matesic et al. 2008 itch−/− mice develop an autoimmune-like disease characterized histologically by a mixed infiltrate in nearly every organ system, lymphoproliferation resulting in splenomegaly and lymphadenopathy, and cortical atrophy of the thymus; the KO mice also produce antinuclear antibodies. |
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| Autoinflammatory disorders v2.29 | ITCH |
Ida Ertmanska commented on gene: ITCH: Comment on list classification: There are at least 14 patients from 5 unrelated families with biallelic variants in ITCH. ITCH deficiency may result in multi-systemic immune dysregulation (present in 9/14 reported patients), dysmorphic features (14/14), developmental delay (14/14), relative macrocephaly (13/14), chronic lung disease (13/14), hepatomegaly/splenomegaly (10/14), and hypotonia (8/14). Based on available evidence, ITCH should be rated Green for autoinflammatory disorders. |
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| Autoinflammatory disorders v2.29 | ITCH |
Ida Ertmanska changed review comment from: As reviewed by Nicholas Head, this gene is already Green on the Primary immunodeficiency or monogenic inflammatory bowel disease panel. ITCH is associated with AR Autoimmune disease, multisystem, with facial dysmorphism, OMIM:613385 (accessed 10th Oct 2025). PMID: 36338154 Wolfe et al., 2022 20yo non-consanguineous Caucasian female with novel ITCH variants: c.599dupC; p.(Ser201Ilefs*8) & deletion of exons 24 and 25. Phenotype: dysmorphic facial features, autoimmune disease including polymyositis, enteropathy, arthritis, psoriasis, hepatitis, and respiratory insufficiency; history of multiple hospitalizations for infections. Muscle biopsy showed 57% of expected mitochondrial DNA copy number but no change in the mitochondrial morphology. Demonstrated mitochondrial energy dysfunction in patient derived ITCH deficient fibroblasts, including reduced oxygen consumption (OCR) and a decrease in cellular ATP production. PMID: 31091003 Brittain et al, 2019 Report of a 23 yo female with biallelic truncating variants ITCH: paternally inherited c.726del; p.(Leu243SerfsTer63) and maternally inherited c.2125_2128del; p.(Glu710PhefsTer2) - neither variant found in gnomAD v4. No known consanguinity. Method: Trio Exome. Phenotype: marked short stature, severe early onset chronic lung disease resembling asthma, dysmorphic facial features, and symmetrical camptodactyly of the fingers but normal intellect. PMID: 30705142 Kleine-Eggebrecht et al., 2019 1-year-old girl of consanguineous parents with a homozygous mutation in ITCH: c.1570-1G > A. Method: trio WES. Phenotype: dystrophy, short stature, psychomotor retardation, and muscular hypotonia, as well as multisystemic autoimmune disease with detection of specific antibodies (de novo autoimmune hepatitis, thyroiditis with exophthalmos, diabetes mellitus type 1, and immune neutropenia). PMID: 20170897 Lohr et al., 2010 Described 10 Amish patients from 8 consanguineous and related families with multisystem autoimmune disease with delayed gross motor and cognitive skills, and facial dysmorphism. 6 of the children had evidence of autoimmune disease, including hypothyroidism in four, autoimmune hepatitis in three, autoimmune enteropathy with chronic diarrhea in two, and one had diabetes. All individuals were homozygous for the variant NM_031483.6(ITCH): c.394dupA p.(Ile132Asnfs) - founder effect. Functional evidence: PMID: 18727493 Matesic et al. 2008 itch−/− mice develop an autoimmune-like disease characterized histologically by a mixed infiltrate in nearly every organ system, lymphoproliferation resulting in splenomegaly and lymphadenopathy, and cortical atrophy of the thymus; the KO mice also produce antinuclear antibodies. Based on the available evidence, ITCH should be rated Green for Autoinflammatory disorders.; to: As reviewed by Nicholas Head, this gene is already Green on the Primary immunodeficiency or monogenic inflammatory bowel disease panel. ITCH is associated with AR Autoimmune disease, multisystem, with facial dysmorphism, OMIM:613385 (accessed 10th Oct 2025). PMID: 36338154 Wolfe et al., 2022 20yo non-consanguineous Caucasian female with novel ITCH variants: c.599dupC; p.(Ser201Ilefs*8) & deletion of exons 24 and 25. Phenotype: dysmorphic facial features, autoimmune disease including polymyositis, enteropathy, arthritis, psoriasis, hepatitis, and respiratory insufficiency; history of multiple hospitalizations for infections. Muscle biopsy showed 57% of expected mitochondrial DNA copy number but no change in the mitochondrial morphology. Demonstrated mitochondrial energy dysfunction in patient derived ITCH deficient fibroblasts, including reduced oxygen consumption (OCR) and a decrease in cellular ATP production. PMID: 33894394 Patel et al., 2022 Male patient compound heterozygous NM_001257137(ITCH): (c.337+2T>C) and (c.772C>T; p.Arg258*). Method: WES. Phenotype: multi-system immune dysregulation presenting with growth failure, very early onset inflammatory bowel disease (VEO-IBD), arthritis, uveitis, psoriasis and type 1 diabetes mellitus. Reported reduced expression of ITCH mRNA and absent ITCH protein. Immune dysregulation was successfully treated with hematopoietic cell transplantation. PMID: 31091003 Brittain et al, 2019 Report of a 23 yo female with biallelic truncating variants ITCH: paternally inherited c.726del; p.(Leu243SerfsTer63) and maternally inherited c.2125_2128del; p.(Glu710PhefsTer2) - neither variant found in gnomAD v4. No known consanguinity. Method: Trio Exome. Phenotype: marked short stature, severe early onset chronic lung disease resembling asthma, dysmorphic facial features, and symmetrical camptodactyly of the fingers but normal intellect. PMID: 30705142 Kleine-Eggebrecht et al., 2019 1-year-old girl of consanguineous parents with a homozygous mutation in ITCH: c.1570-1G > A. Method: trio WES. Phenotype: dystrophy, short stature, psychomotor retardation, and muscular hypotonia, as well as multisystemic autoimmune disease with detection of specific antibodies (de novo autoimmune hepatitis, thyroiditis with exophthalmos, diabetes mellitus type 1, and immune neutropenia). PMID: 20170897 Lohr et al., 2010 Described 10 Amish patients from 8 consanguineous and related families with multisystem autoimmune disease with delayed gross motor and cognitive skills, and facial dysmorphism. 6 of the children had evidence of autoimmune disease, including hypothyroidism in four, autoimmune hepatitis in three, autoimmune enteropathy with chronic diarrhea in two, and one had diabetes. All individuals were homozygous for the variant NM_031483.6(ITCH): c.394dupA p.(Ile132Asnfs) - founder effect. Functional evidence: PMID: 18727493 Matesic et al. 2008 itch−/− mice develop an autoimmune-like disease characterized histologically by a mixed infiltrate in nearly every organ system, lymphoproliferation resulting in splenomegaly and lymphadenopathy, and cortical atrophy of the thymus; the KO mice also produce antinuclear antibodies. |
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| Autoinflammatory disorders v2.29 | ITCH |
Ida Ertmanska changed review comment from: As reviewed by Nicholas Head, this gene is already Green on the Primary immunodeficiency or monogenic inflammatory bowel disease panel. ITCH is associated with AR Autoimmune disease, multisystem, with facial dysmorphism, OMIM:613385 (accessed 10th Oct 2025). PMID: 36338154 Wolfe et al., 2022 20yo non-consanguineous Caucasian female with novel ITCH variants: c.599dupC; p.(Ser201Ilefs*8) & deletion of exons 24 and 25. Phenotype: dysmorphic facial features, autoimmune disease including polymyositis, enteropathy, arthritis, psoriasis, hepatitis, and respiratory insufficiency; history of multiple hospitalizations for infections. Muscle biopsy showed 57% of expected mitochondrial DNA copy number but no change in the mitochondrial morphology. Demonstrated mitochondrial energy dysfunction in patient derived ITCH deficient fibroblasts, including reduced oxygen consumption (OCR), flux through fatty acid oxidation, and a decrease in cellular ATP production. PMID: 31091003 Brittain et al, 2019 Report of a 23 yo female with biallelic truncating variants ITCH: paternally inherited c.726del; p.(Leu243SerfsTer63) and maternally inherited c.2125_2128del; p.(Glu710PhefsTer2) - neither variant found in gnomAD v4. No known consanguinity. Method: Trio Exome. Phenotype: marked short stature, severe early onset chronic lung disease resembling asthma, dysmorphic facial features, and symmetrical camptodactyly of the fingers but normal intellect. PMID: 30705142 Kleine-Eggebrecht et al., 2019 1-year-old girl of consanguineous parents with a homozygous mutation in ITCH: c.1570-1G > A. Method: trio WES. Phenotype: dystrophy, short stature, psychomotor retardation, and muscular hypotonia, as well as multisystemic autoimmune disease with detection of specific antibodies (de novo autoimmune hepatitis, thyroiditis with exophthalmos, diabetes mellitus type 1, and immune neutropenia). PMID: 20170897 Lohr et al., 2010 Described 10 Amish patients from 8 consanguineous and related families with multisystem autoimmune disease with delayed gross motor and cognitive skills, and facial dysmorphism. 6 of the children had evidence of autoimmune disease, including hypothyroidism in four, autoimmune hepatitis in three, autoimmune enteropathy with chronic diarrhea in two, and one had diabetes. All individuals were homozygous for the variant NM_031483.6(ITCH): c.394dupA p.(Ile132Asnfs) - founder effect. Functional evidence: PMID: 18727493 Matesic et al. 2008 itch−/− mice develop an autoimmune-like disease characterized histologically by a mixed infiltrate in nearly every organ system, lymphoproliferation resulting in splenomegaly and lymphadenopathy, and cortical atrophy of the thymus; the KO mice also produce antinuclear antibodies. Based on the available evidence, ITCH should be rated Green for Autoinflammatory disorders.; to: As reviewed by Nicholas Head, this gene is already Green on the Primary immunodeficiency or monogenic inflammatory bowel disease panel. ITCH is associated with AR Autoimmune disease, multisystem, with facial dysmorphism, OMIM:613385 (accessed 10th Oct 2025). PMID: 36338154 Wolfe et al., 2022 20yo non-consanguineous Caucasian female with novel ITCH variants: c.599dupC; p.(Ser201Ilefs*8) & deletion of exons 24 and 25. Phenotype: dysmorphic facial features, autoimmune disease including polymyositis, enteropathy, arthritis, psoriasis, hepatitis, and respiratory insufficiency; history of multiple hospitalizations for infections. Muscle biopsy showed 57% of expected mitochondrial DNA copy number but no change in the mitochondrial morphology. Demonstrated mitochondrial energy dysfunction in patient derived ITCH deficient fibroblasts, including reduced oxygen consumption (OCR) and a decrease in cellular ATP production. PMID: 31091003 Brittain et al, 2019 Report of a 23 yo female with biallelic truncating variants ITCH: paternally inherited c.726del; p.(Leu243SerfsTer63) and maternally inherited c.2125_2128del; p.(Glu710PhefsTer2) - neither variant found in gnomAD v4. No known consanguinity. Method: Trio Exome. Phenotype: marked short stature, severe early onset chronic lung disease resembling asthma, dysmorphic facial features, and symmetrical camptodactyly of the fingers but normal intellect. PMID: 30705142 Kleine-Eggebrecht et al., 2019 1-year-old girl of consanguineous parents with a homozygous mutation in ITCH: c.1570-1G > A. Method: trio WES. Phenotype: dystrophy, short stature, psychomotor retardation, and muscular hypotonia, as well as multisystemic autoimmune disease with detection of specific antibodies (de novo autoimmune hepatitis, thyroiditis with exophthalmos, diabetes mellitus type 1, and immune neutropenia). PMID: 20170897 Lohr et al., 2010 Described 10 Amish patients from 8 consanguineous and related families with multisystem autoimmune disease with delayed gross motor and cognitive skills, and facial dysmorphism. 6 of the children had evidence of autoimmune disease, including hypothyroidism in four, autoimmune hepatitis in three, autoimmune enteropathy with chronic diarrhea in two, and one had diabetes. All individuals were homozygous for the variant NM_031483.6(ITCH): c.394dupA p.(Ile132Asnfs) - founder effect. Functional evidence: PMID: 18727493 Matesic et al. 2008 itch−/− mice develop an autoimmune-like disease characterized histologically by a mixed infiltrate in nearly every organ system, lymphoproliferation resulting in splenomegaly and lymphadenopathy, and cortical atrophy of the thymus; the KO mice also produce antinuclear antibodies. Based on the available evidence, ITCH should be rated Green for Autoinflammatory disorders. |
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| Autoinflammatory disorders v2.29 | ITCH | Ida Ertmanska edited their review of gene: ITCH: Changed publications to: 20170897, 30705142, 31091003, 36338154 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Autoinflammatory disorders v2.29 | ITCH |
Ida Ertmanska changed review comment from: As reviewed by Nicholas Head, this gene is already Green on the Primary immunodeficiency or monogenic inflammatory bowel disease panel. ITCH is associated with AR Autoimmune disease, multisystem, with facial dysmorphism, OMIM:613385 (accessed 10th Oct 2025). PMID: 31091003 Brittain et al, 2019 Report of a 23 yo female with biallelic truncating variants ITCH: paternally inherited c.726del; p.(Leu243SerfsTer63) and maternally inherited c.2125_2128del; p.(Glu710PhefsTer2) - neither variant found in gnomAD v4. No known consanguinity. Method: Trio Exome. Phenotype: marked short stature, severe early onset chronic lung disease resembling asthma, dysmorphic facial features, and symmetrical camptodactyly of the fingers but normal intellect. PMID: 30705142 Kleine-Eggebrecht et al., 2019 1-year-old girl of consanguineous parents with a mutation in ITCH. Phenotype: dystrophy, short stature, psychomotor retardation, and muscular hypotonia, as well as systemic autoimmune disease with detection of specific antibodies (de novo autoimmune hepatitis, thyroiditis with exophthalmos, diabetes mellitus type 1, and immune neutropenia). No access to full article. PMID: 20170897 Lohr et al., 2010 Described 10 Amish patients from 8 consanguineous and related families with multisystem autoimmune disease with delayed gross motor and cognitive skills, and facial dysmorphism. 6 of the children had evidence of autoimmune disease, including hypothyroidism in four, autoimmune hepatitis in three, autoimmune enteropathy with chronic diarrhea in two, and one had diabetes. All individuals were homozygous for the variant NM_031483.6(ITCH): c.394dupA p.(Ile132Asnfs) - founder effect. Functional evidence: PMID: 18727493 Matesic et al. 2008 itch−/− mice develop an autoimmune-like disease characterized histologically by a mixed infiltrate in nearly every organ system, lymphoproliferation resulting in splenomegaly and lymphadenopathy, and cortical atrophy of the thymus; the KO mice also produce antinuclear antibodies. Based on the available evidence, ITCH should be rated Green for Autoinflammatory disorders.; to: As reviewed by Nicholas Head, this gene is already Green on the Primary immunodeficiency or monogenic inflammatory bowel disease panel. ITCH is associated with AR Autoimmune disease, multisystem, with facial dysmorphism, OMIM:613385 (accessed 10th Oct 2025). PMID: 36338154 Wolfe et al., 2022 20yo non-consanguineous Caucasian female with novel ITCH variants: c.599dupC; p.(Ser201Ilefs*8) & deletion of exons 24 and 25. Phenotype: dysmorphic facial features, autoimmune disease including polymyositis, enteropathy, arthritis, psoriasis, hepatitis, and respiratory insufficiency; history of multiple hospitalizations for infections. Muscle biopsy showed 57% of expected mitochondrial DNA copy number but no change in the mitochondrial morphology. Demonstrated mitochondrial energy dysfunction in patient derived ITCH deficient fibroblasts, including reduced oxygen consumption (OCR), flux through fatty acid oxidation, and a decrease in cellular ATP production. PMID: 31091003 Brittain et al, 2019 Report of a 23 yo female with biallelic truncating variants ITCH: paternally inherited c.726del; p.(Leu243SerfsTer63) and maternally inherited c.2125_2128del; p.(Glu710PhefsTer2) - neither variant found in gnomAD v4. No known consanguinity. Method: Trio Exome. Phenotype: marked short stature, severe early onset chronic lung disease resembling asthma, dysmorphic facial features, and symmetrical camptodactyly of the fingers but normal intellect. PMID: 30705142 Kleine-Eggebrecht et al., 2019 1-year-old girl of consanguineous parents with a homozygous mutation in ITCH: c.1570-1G > A. Method: trio WES. Phenotype: dystrophy, short stature, psychomotor retardation, and muscular hypotonia, as well as multisystemic autoimmune disease with detection of specific antibodies (de novo autoimmune hepatitis, thyroiditis with exophthalmos, diabetes mellitus type 1, and immune neutropenia). PMID: 20170897 Lohr et al., 2010 Described 10 Amish patients from 8 consanguineous and related families with multisystem autoimmune disease with delayed gross motor and cognitive skills, and facial dysmorphism. 6 of the children had evidence of autoimmune disease, including hypothyroidism in four, autoimmune hepatitis in three, autoimmune enteropathy with chronic diarrhea in two, and one had diabetes. All individuals were homozygous for the variant NM_031483.6(ITCH): c.394dupA p.(Ile132Asnfs) - founder effect. Functional evidence: PMID: 18727493 Matesic et al. 2008 itch−/− mice develop an autoimmune-like disease characterized histologically by a mixed infiltrate in nearly every organ system, lymphoproliferation resulting in splenomegaly and lymphadenopathy, and cortical atrophy of the thymus; the KO mice also produce antinuclear antibodies. Based on the available evidence, ITCH should be rated Green for Autoinflammatory disorders. |
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| Autoinflammatory disorders v2.29 | ITCH |
Ida Ertmanska changed review comment from: As reviewed by Nicholas Head, this gene is already Green on the Primary immunodeficiency or monogenic inflammatory bowel disease panel. ITCH is associated with AR Autoimmune disease, multisystem, with facial dysmorphism, OMIM:613385 (accessed 10th Oct 2025). PMID: 31091003 Brittain et al, 2019 Report of a 23 yo female with biallelic truncating variants ITCH: paternally inherited c.726del; p.(Leu243SerfsTer63) and maternally inherited c.2125_2128del; p.(Glu710PhefsTer2) - neither variant found in gnomAD v4. Method: Trio Exome. Phenotype: marked short stature, severe early onset chronic lung disease resembling asthma, dysmorphic facial features, and symmetrical camptodactyly of the fingers but normal intellect. PMID: 30705142 Kleine-Eggebrecht et al., 2019 1-year-old girl of consanguineous parents with a mutation in ITCH. Phenotype: dystrophy, short stature, psychomotor retardation, and muscular hypotonia, as well as systemic autoimmune disease with detection of specific antibodies (de novo autoimmune hepatitis, thyroiditis with exophthalmos, diabetes mellitus type 1, and immune neutropenia). No access to full article. PMID: 20170897 Lohr et al., 2010 Described 10 Amish patients from 8 consanguineous and related families with multisystem autoimmune disease with facial dysmorphism. 6 of the children had evidence of autoimmune disease, including hypothyroidism in four, autoimmune hepatitis in three, autoimmune enteropathy with chronic diarrhea in two, and one had diabetes. All individuals were homozygous for the variant NM_031483.6(ITCH): c.394dupA p.(Ile132Asnfs) - founder effect. Based on the available evidence, ITCH should be rated Green for Autoinflammatory disorders.; to: As reviewed by Nicholas Head, this gene is already Green on the Primary immunodeficiency or monogenic inflammatory bowel disease panel. ITCH is associated with AR Autoimmune disease, multisystem, with facial dysmorphism, OMIM:613385 (accessed 10th Oct 2025). PMID: 31091003 Brittain et al, 2019 Report of a 23 yo female with biallelic truncating variants ITCH: paternally inherited c.726del; p.(Leu243SerfsTer63) and maternally inherited c.2125_2128del; p.(Glu710PhefsTer2) - neither variant found in gnomAD v4. No known consanguinity. Method: Trio Exome. Phenotype: marked short stature, severe early onset chronic lung disease resembling asthma, dysmorphic facial features, and symmetrical camptodactyly of the fingers but normal intellect. PMID: 30705142 Kleine-Eggebrecht et al., 2019 1-year-old girl of consanguineous parents with a mutation in ITCH. Phenotype: dystrophy, short stature, psychomotor retardation, and muscular hypotonia, as well as systemic autoimmune disease with detection of specific antibodies (de novo autoimmune hepatitis, thyroiditis with exophthalmos, diabetes mellitus type 1, and immune neutropenia). No access to full article. PMID: 20170897 Lohr et al., 2010 Described 10 Amish patients from 8 consanguineous and related families with multisystem autoimmune disease with delayed gross motor and cognitive skills, and facial dysmorphism. 6 of the children had evidence of autoimmune disease, including hypothyroidism in four, autoimmune hepatitis in three, autoimmune enteropathy with chronic diarrhea in two, and one had diabetes. All individuals were homozygous for the variant NM_031483.6(ITCH): c.394dupA p.(Ile132Asnfs) - founder effect. Functional evidence: PMID: 18727493 Matesic et al. 2008 itch−/− mice develop an autoimmune-like disease characterized histologically by a mixed infiltrate in nearly every organ system, lymphoproliferation resulting in splenomegaly and lymphadenopathy, and cortical atrophy of the thymus; the KO mice also produce antinuclear antibodies. Based on the available evidence, ITCH should be rated Green for Autoinflammatory disorders. |
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| Autoinflammatory disorders v2.29 | ITCH | Ida Ertmanska reviewed gene: ITCH: Rating: GREEN; Mode of pathogenicity: None; Publications: 20170897, 30705142, 31091003; Phenotypes: Autoimmune disease, multisystem, with facial dysmorphism, OMIM:613385; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Autoinflammatory disorders v2.29 | ITCH |
Nicholas Head gene: ITCH was added gene: ITCH was added to Autoinflammatory disorders. Sources: Other Mode of inheritance for gene: ITCH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ITCH were set to PMID: 36338154 Phenotypes for gene: ITCH were set to Autoimmune disease, multisystem, with facial dysmorphism, 613385 Review for gene: ITCH was set to GREEN gene: ITCH was marked as current diagnostic Added comment: Currently listed as a green gene on R15 panel. Causes a autoinflammatory disorder with multisystem involvement. Sources: Other |
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| Autoinflammatory disorders v2.10 | ELF4 |
Achchuthan Shanmugasundram edited their review of gene: ELF4: Added comment: PMID:34326534 - Two variants identified in three unrelated males with autoinflammatory disease characterised by fever, oral ulcers and mucosal inflammation. Supported by functional studies and mouse model. PMID:35266071 - Paediatric male patient identified with a hemizygous variant and was suffering from recurrent viral and bacterial respiratory infection, refractory oral ulcer, constipation, and arthritis. Supported by functional studies and mouse model. PMID:36823308 - Five more male patients presenting mainly with oral ulcer, inflammatory bowel disease-like symptoms, fever of unknown origin, anaemia, or systemic lupus erythematosus. PMID:38231408 - An international cohort of fourteen patients exhibiting a heterogeneous clinical phenotype including weight loss, oral and gastrointestinal aphthous ulcers, fevers, skin inflammation, gastrointestinal symptoms, arthritis, arthralgia, and myalgia, with findings of increased inflammatory markers, anaemia, neutrophilic leukocytosis, thrombocytosis, intermittently low natural killer and class-switched memory B cells, and increased inflammatory cytokines in the serum. PMID:38773005 - A 11-year-old boy presented with a Behcet's-like phenotype including elevated inflammatory indicators, ileocecal ulcers and inflammatory cell infiltrations. The patient was treated with long-term immunosuppressant and TNF-alpha blocker. Supporting functional studies available. PMID:39563044 - Two male patients presented with recurrent oral ulcers and abdominal pain and had significant increase in inflammatory markers, multiple intestinal ulcers, and both patients developed intestinal fistulas. PMID:39976696 - Three unrelated paediatric female patients, who are all heterozygous for ELF4 variants. Similar to reported male patients, the main clinical features include recurring oral ulcers, abdominal pain and diarrhoea with colonoscopy showing ulcers in the colon. Skewed X chromosome inactivation patterns were observed in all three female patients, with over-inactivation of the X chromosome carrying the wild-type allele confirmed in two of them.; Changed publications to: 34326534, 35266071, 36823308, 38231408, 38773005, 39563044, 39976696 |
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