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| Ectodermal dysplasia v4.21 | MSX1 |
Ida Ertmanska changed review comment from: BIALLELIC CASE REPORTS: PMID: 25565750 Ceyhan et al., 2014 Report of 5 heterozygotes and 1 homozygote; MSX1 variants reported: c.119C>G, p.Ala40Gly; c.347C>T, p.(Gly116Gly); c.463C>A, p.(Pro155Glu); c.95C>T, p.(Ala32Val); c*6C>T (3' UTR region, homozygous). c*6C>T is common in population (MAF = 0.3962 in gnomAD, with total of 41187 homozygotes reported). Only MSX1 was sequenced in all patients. PMID: 24031111 Ghaderi et al., 2013 Case report - 2.5-year-old boy with early exfoliation of the primary canine, absence of the primary incisors, and nail dysplasia (Witkop syndrome). Homozygous mutation was identified in 3'-UTR of MSX1 of proband (*6C>T), het parents unaffected. Analysed two coding exons, exon-intron boundaries, and part of 3’-UTR of MSX1 only. PMID: 16932841 Chishti et al., 2006 2 distantly related Pakistani pedigrees with recessive mutation p.Ala219Thr (?), segregating with oligodontia and other dental anomalies. Method: linkage analysis in the pedigree followed by direct MSX1 sequencing. MSX1 is associated with 3 autosomal dominant disease entities in OMIM: Ectodermal dysplasia 3, Witkop type, 189500; Orofacial cleft 5, 608874; Tooth agenesis, selective, 1, with or without orofacial cleft, 106600 (OMIM accessed 12th Feb 2026). ClinGen Expert Panels have classified the link between MSX1 and AD tooth agenesis, selective, 1 as Definitive (Feb 2024), but AD tooth and nail syndrome has been classified as Disputed (Oct 2023).; to: BIALLELIC CASE REPORTS: PMID: 25565750 Ceyhan et al., 2014 Report of Turkish cases with non-syndromic tooth agenesis and other dental anomalies: 5 heterozygotes and 1 homozygote; MSX1 variants reported: c.119C>G, p.Ala40Gly; c.347C>T, p.(Gly116Gly); c.463C>A, p.(Pro155Glu); c.95C>T, p.(Ala32Val); c*6C>T (3' UTR region, homozygous). c*6C>T is common in population (MAF = 0.3962 in gnomAD, with total of 41187 homozygotes reported). Only MSX1 was sequenced in all patients. PMID: 24031111 Ghaderi et al., 2013 Case report - 2.5-year-old boy with early exfoliation of the primary canine, absence of the primary incisors, and nail dysplasia (Witkop syndrome). Homozygous mutation was identified in 3'-UTR of MSX1 of proband (*6C>T), het parents unaffected. Analysed two coding exons, exon-intron boundaries, and part of 3’-UTR of MSX1 only. PMID: 16932841 Chishti et al., 2006 2 distantly related Pakistani pedigrees with recessive mutation p.Ala219Thr (?), segregating with oligodontia and other dental anomalies. Method: linkage analysis in the pedigree followed by direct MSX1 sequencing. MSX1 is associated with 3 autosomal dominant disease entities in OMIM: Ectodermal dysplasia 3, Witkop type, 189500; Orofacial cleft 5, 608874; Tooth agenesis, selective, 1, with or without orofacial cleft, 106600 (OMIM accessed 12th Feb 2026). ClinGen Expert Panels have classified the link between MSX1 and AD tooth agenesis, selective, 1 as Definitive (Feb 2024), but AD tooth and nail syndrome has been classified as Disputed (Oct 2023). |
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| Ectodermal dysplasia v4.21 | MSX1 |
Ida Ertmanska changed review comment from: PMID: 25565750 Ceyhan et al., 2014 Report of 5 heterozygotes and 1 homozygote; MSX1 variants reported: c.119C>G, p.Ala40Gly; c.347C>T, p.(Gly116Gly); c.463C>A, p.(Pro155Glu); c.95C>T, p.(Ala32Val); c*6C>T (3' UTR region, homozygous). c*6C>T is common in population (MAF = 0.3962 in gnomAD, with total of 41187 homozygotes reported). Only MSX1 was sequenced in all patients. PMID: 24031111 Ghaderi et al., 2013 Case report - 2.5-year-old boy with early exfoliation of the primary canine, absence of the primary incisors, and nail dysplasia (Witkop syndrome). Homozygous mutation was identified in 3'-UTR of MSX1 of proband (*6C>T), het parents unaffected. Analysed two coding exons, exon-intron boundaries, and part of 3’-UTR of MSX1 only. PMID: 16932841 Chishti et al., 2006 2 distantly related Pakistani pedigrees with recessive mutation p.Ala219Thr (?), segregating with oligodontia and other dental anomalies. Method: linkage analysis in the pedigree followed by direct MSX1 sequencing. MSX1 is associated with 3 autosomal dominant disease entities in OMIM: Ectodermal dysplasia 3, Witkop type, 189500; Orofacial cleft 5, 608874; Tooth agenesis, selective, 1, with or without orofacial cleft, 106600 (OMIM accessed 12th Feb 2026). ClinGen Expert Panels have classified the link between MSX1 and AD tooth agenesis, selective, 1 as Definitive (Feb 2024), but AD tooth and nail syndrome has been classified as Disputed (Oct 2023).; to: BIALLELIC CASE REPORTS: PMID: 25565750 Ceyhan et al., 2014 Report of 5 heterozygotes and 1 homozygote; MSX1 variants reported: c.119C>G, p.Ala40Gly; c.347C>T, p.(Gly116Gly); c.463C>A, p.(Pro155Glu); c.95C>T, p.(Ala32Val); c*6C>T (3' UTR region, homozygous). c*6C>T is common in population (MAF = 0.3962 in gnomAD, with total of 41187 homozygotes reported). Only MSX1 was sequenced in all patients. PMID: 24031111 Ghaderi et al., 2013 Case report - 2.5-year-old boy with early exfoliation of the primary canine, absence of the primary incisors, and nail dysplasia (Witkop syndrome). Homozygous mutation was identified in 3'-UTR of MSX1 of proband (*6C>T), het parents unaffected. Analysed two coding exons, exon-intron boundaries, and part of 3’-UTR of MSX1 only. PMID: 16932841 Chishti et al., 2006 2 distantly related Pakistani pedigrees with recessive mutation p.Ala219Thr (?), segregating with oligodontia and other dental anomalies. Method: linkage analysis in the pedigree followed by direct MSX1 sequencing. MSX1 is associated with 3 autosomal dominant disease entities in OMIM: Ectodermal dysplasia 3, Witkop type, 189500; Orofacial cleft 5, 608874; Tooth agenesis, selective, 1, with or without orofacial cleft, 106600 (OMIM accessed 12th Feb 2026). ClinGen Expert Panels have classified the link between MSX1 and AD tooth agenesis, selective, 1 as Definitive (Feb 2024), but AD tooth and nail syndrome has been classified as Disputed (Oct 2023). |
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| Ectodermal dysplasia v4.21 | MSX1 |
Ida Ertmanska changed review comment from: PMID: 25565750 Ceyhan et al., 2014 Report of 5 heterozygotes and 1 homozygote; MSX1 variants reported: c.119C>G, p.Ala40Gly; c.347C>T, p.(Gly116Gly); c.463C>A, p.(Pro155Glu); c.95C>T, p.(Ala32Val); c*6C>T (3' UTR region, homozygous). c*6C>T is common in population (MAF = 0.3962 in gnomAD, with total of 41187 homozygotes reported). Only MSX1 was sequenced in all patients. PMID: 24031111 Ghaderi et al., 2013 Case report - 2.5-year-old boy with early exfoliation of the primary canine, absence of the primary incisors, and nail dysplasia (Witkop syndrome). Homozygous mutation was identified in 3'-UTR of MSX1 of proband (*6C>T), het parents unaffected. Analysed two coding exons, exon-intron boundaries, and part of 3’-UTR of MSX1 only. PMID: 16932841 Chishti et al., 2006 2 distantly related Pakistani pedigrees with recessive mutation p.Ala219Thr (?), segregating with oligodontia and other dental anomalies. Method: linkage analysis in the pedigree followed by direct MSX1 sequencing. MSX1 is associated with 3 autosomal dominant disease entities in OMIM: Ectodermal dysplasia 3, Witkop type, 189500; Orofacial cleft 5, 608874; Tooth agenesis, selective, 1, with or without orofacial cleft, 106600 (OMIM accessed 12th Feb 2026).; to: PMID: 25565750 Ceyhan et al., 2014 Report of 5 heterozygotes and 1 homozygote; MSX1 variants reported: c.119C>G, p.Ala40Gly; c.347C>T, p.(Gly116Gly); c.463C>A, p.(Pro155Glu); c.95C>T, p.(Ala32Val); c*6C>T (3' UTR region, homozygous). c*6C>T is common in population (MAF = 0.3962 in gnomAD, with total of 41187 homozygotes reported). Only MSX1 was sequenced in all patients. PMID: 24031111 Ghaderi et al., 2013 Case report - 2.5-year-old boy with early exfoliation of the primary canine, absence of the primary incisors, and nail dysplasia (Witkop syndrome). Homozygous mutation was identified in 3'-UTR of MSX1 of proband (*6C>T), het parents unaffected. Analysed two coding exons, exon-intron boundaries, and part of 3’-UTR of MSX1 only. PMID: 16932841 Chishti et al., 2006 2 distantly related Pakistani pedigrees with recessive mutation p.Ala219Thr (?), segregating with oligodontia and other dental anomalies. Method: linkage analysis in the pedigree followed by direct MSX1 sequencing. MSX1 is associated with 3 autosomal dominant disease entities in OMIM: Ectodermal dysplasia 3, Witkop type, 189500; Orofacial cleft 5, 608874; Tooth agenesis, selective, 1, with or without orofacial cleft, 106600 (OMIM accessed 12th Feb 2026). ClinGen Expert Panels have classified the link between MSX1 and AD tooth agenesis, selective, 1 as Definitive (Feb 2024), but AD tooth and nail syndrome has been classified as Disputed (Oct 2023). |
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| Ectodermal dysplasia v4.21 | MSX1 |
Ida Ertmanska changed review comment from: PMID: 25565750 Ceyhan et al., 2014 Report of 5 heterozygotes and 1 homozygote; MSX1 variants reported: c.119C>G, p.Ala40Gly; c.347C>T, p.(Gly116Gly); c.463C>A, p.(Pro155Glu); c.95C>T, p.(Ala32Val); c*6C>T (3' UTR region, homozygous). c*6C>T is common in population (MAF = 0.3962 in gnomAD, with total of 41187 homozygotes reported). PMID: 24031111 Ghaderi et al., 2013 Case report - 2.5-year-old boy with early exfoliation of the primary canine, absence of the primary incisors, and nail dysplasia (Witkop syndrome). Homozygous mutation was identified in 3'-UTR of MSX1 of proband (*6C>T), het parents unaffected. PMID: 16932841 Chishti et al., 2006 2 distantly related Pakistani pedigrees with recessive mutation p.Ala219Thr (?), segregating with oligodontia and other dental anomalies. MSX1 is associated with 3 autosomal dominant disease entities in OMIM: Ectodermal dysplasia 3, Witkop type, 189500; Orofacial cleft 5, 608874; Tooth agenesis, selective, 1, with or without orofacial cleft, 106600 (OMIM accessed 12th Feb 2026).; to: PMID: 25565750 Ceyhan et al., 2014 Report of 5 heterozygotes and 1 homozygote; MSX1 variants reported: c.119C>G, p.Ala40Gly; c.347C>T, p.(Gly116Gly); c.463C>A, p.(Pro155Glu); c.95C>T, p.(Ala32Val); c*6C>T (3' UTR region, homozygous). c*6C>T is common in population (MAF = 0.3962 in gnomAD, with total of 41187 homozygotes reported). Only MSX1 was sequenced in all patients. PMID: 24031111 Ghaderi et al., 2013 Case report - 2.5-year-old boy with early exfoliation of the primary canine, absence of the primary incisors, and nail dysplasia (Witkop syndrome). Homozygous mutation was identified in 3'-UTR of MSX1 of proband (*6C>T), het parents unaffected. Analysed two coding exons, exon-intron boundaries, and part of 3’-UTR of MSX1 only. PMID: 16932841 Chishti et al., 2006 2 distantly related Pakistani pedigrees with recessive mutation p.Ala219Thr (?), segregating with oligodontia and other dental anomalies. Method: linkage analysis in the pedigree followed by direct MSX1 sequencing. MSX1 is associated with 3 autosomal dominant disease entities in OMIM: Ectodermal dysplasia 3, Witkop type, 189500; Orofacial cleft 5, 608874; Tooth agenesis, selective, 1, with or without orofacial cleft, 106600 (OMIM accessed 12th Feb 2026). |
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| Ectodermal dysplasia v4.21 | MSX1 |
Ida Ertmanska changed review comment from: PMID: 25565750 Ceyhan et al., 2014 Report of 5 heterozygotes and 1 homozygote; MSX1 variants reported: c.119C>G, p.Ala40Gly; c.347C>T, p.(Gly116Gly); c.463C>A, p.(Pro155Glu); c.95C>T, p.(Ala32Val); c*6C>T (3' UTR region, homozygous). c*6C>T is common in population (MAF = 0.3962 in gnomAD, with total of 41187 homozygotes reported). PMID: 24031111 Ghaderi et al., 2013 Case report - 2.5-year-old boy with early exfoliation of the primary canine, absence of the primary incisors, and nail dysplasia. Homozygous mutation was identified in 3'-UTR of MSX1 of proband (*6C>T), het parents unaffected. PMID: 16932841 Chishti et al., 2006 2 distantly related Pakistani pedigrees with recessive mutation p.Ala219Thr (?), segregating with oligodontia and other dental anomalies. MSX1 is associated with 3 autosomal dominant disease entities in OMIM: Ectodermal dysplasia 3, Witkop type, 189500; Orofacial cleft 5, 608874; Tooth agenesis, selective, 1, with or without orofacial cleft, 106600 (OMIM accessed 12th Feb 2026).; to: PMID: 25565750 Ceyhan et al., 2014 Report of 5 heterozygotes and 1 homozygote; MSX1 variants reported: c.119C>G, p.Ala40Gly; c.347C>T, p.(Gly116Gly); c.463C>A, p.(Pro155Glu); c.95C>T, p.(Ala32Val); c*6C>T (3' UTR region, homozygous). c*6C>T is common in population (MAF = 0.3962 in gnomAD, with total of 41187 homozygotes reported). PMID: 24031111 Ghaderi et al., 2013 Case report - 2.5-year-old boy with early exfoliation of the primary canine, absence of the primary incisors, and nail dysplasia (Witkop syndrome). Homozygous mutation was identified in 3'-UTR of MSX1 of proband (*6C>T), het parents unaffected. PMID: 16932841 Chishti et al., 2006 2 distantly related Pakistani pedigrees with recessive mutation p.Ala219Thr (?), segregating with oligodontia and other dental anomalies. MSX1 is associated with 3 autosomal dominant disease entities in OMIM: Ectodermal dysplasia 3, Witkop type, 189500; Orofacial cleft 5, 608874; Tooth agenesis, selective, 1, with or without orofacial cleft, 106600 (OMIM accessed 12th Feb 2026). |
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| Ectodermal dysplasia v4.21 | MSX1 |
Ida Ertmanska changed review comment from: PMID: 25565750 Ceyhan et al., 2014 Report of 5 heterozygotes and 1 homozygote; MSX1 variants reported: c.119C>G, p.Ala40Gly; c.347C>T, p.(Gly116Gly); c.463C>A, p.(Pro155Glu); c.95C>T, p.(Ala32Val); c*6C>T (3' UTR region, homozygous). c*6C>T is common in population (MAF = 0.3962 in gnomAD, with total of 41187 homozygotes reported). PMID: 24031111 Ghaderi et al., 2013 Case report - 2.5-year-old boy with early exfoliation of the primary canine, absence of the primary incisors, and nail dysplasia. Homozygous mutation was identified in 3'-UTR of MSX1 of proband (*6C>T), het parents unaffected. PMID: 16932841 Chishti et al., 2006 2 distantly related Pakistani pedigrees with recessive mutation p.Ala219Thr (?), segregating with oligodontia and other dental anomalies.; to: PMID: 25565750 Ceyhan et al., 2014 Report of 5 heterozygotes and 1 homozygote; MSX1 variants reported: c.119C>G, p.Ala40Gly; c.347C>T, p.(Gly116Gly); c.463C>A, p.(Pro155Glu); c.95C>T, p.(Ala32Val); c*6C>T (3' UTR region, homozygous). c*6C>T is common in population (MAF = 0.3962 in gnomAD, with total of 41187 homozygotes reported). PMID: 24031111 Ghaderi et al., 2013 Case report - 2.5-year-old boy with early exfoliation of the primary canine, absence of the primary incisors, and nail dysplasia. Homozygous mutation was identified in 3'-UTR of MSX1 of proband (*6C>T), het parents unaffected. PMID: 16932841 Chishti et al., 2006 2 distantly related Pakistani pedigrees with recessive mutation p.Ala219Thr (?), segregating with oligodontia and other dental anomalies. MSX1 is associated with 3 autosomal dominant disease entities in OMIM: Ectodermal dysplasia 3, Witkop type, 189500; Orofacial cleft 5, 608874; Tooth agenesis, selective, 1, with or without orofacial cleft, 106600 (OMIM accessed 12th Feb 2026). |
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| Ectodermal dysplasia v3.29 | KRT83 |
Arina Puzriakova changed review comment from: Comment on list classification: KRT81 is associated with two relevant phenotypes in OMIM (MIM# 158000) and G2P with a 'definitive' disease confidence classification for monilethrix. Monoallelic variant have been linked to monilethrix in two families (PMID: 15744029; 25557232) while biallelic variants were found in one family with EKVP5 (PMID: 27965375). Overall no additional evidence has been published since the last review and therefore going to maintain the amber rating for now, but adding a 'watchlist' tag to monitor for additional evidence that may lead to future upgrade to green. Other keratin genes, like KRT81 and KRT86 have been added as amber with the recommendation of being made green at the next review.; to: Comment on list classification: KRT83 is associated with two relevant phenotypes in OMIM (MIM# 158000) and G2P with a 'definitive' disease confidence classification for monilethrix. Monoallelic variant have been linked to monilethrix in two families (PMID: 15744029; 25557232) while biallelic variants were found in one family with EKVP5 (PMID: 27965375). Overall no additional evidence has been published since the last review and therefore going to maintain the amber rating for now, but adding a 'watchlist' tag to monitor for additional evidence that may lead to future upgrade to green. Other keratin genes, like KRT81 and KRT86 have been added as amber with the recommendation of being made green at the next review. |
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| Ectodermal dysplasia v3.22 | KRT83 |
Arina Puzriakova Added comment: Comment on list classification: KRT81 is associated with two relevant phenotypes in OMIM (MIM# 158000) and G2P with a 'definitive' disease confidence classification for monilethrix. Monoallelic variant have been linked to monilethrix in two families (PMID: 15744029; 25557232) while biallelic variants were found in one family with EKVP5 (PMID: 27965375). Overall no additional evidence has been published since the last review and therefore going to maintain the amber rating for now, but adding a 'watchlist' tag to monitor for additional evidence that may lead to future upgrade to green. Other keratin genes, like KRT81 and KRT86 have been added as amber with the recommendation of being made green at the next review. |
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| Ectodermal dysplasia v3.19 | KRT81 |
Arina Puzriakova Added comment: Comment on list classification: KRT81 is associated with a relevant phenotype in OMIM (MIM# 158000) and G2P with a 'definitive' disease confidence classification. Monoallelic variant have been linked to monilethrix. In addition to the two families previously discussed (PMID: 9665406; 9402962), there are an additional three unrelated cases reported in the literature (PMID: 10504448; 14714571; 25557232), particularly for recurrent variants at p.Glu413. KRT81 variants have been found in unaffected family members, suggesting reduced penetrance. Overall there are sufficient cases to support an association with monilethrix, and therefore this gene can be promoted to Green at the next GMS panel update. |
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| Ectodermal dysplasia v3.17 | KRT86 | Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Ronnie Wright (NWGLH). KRT86 is associated with a relevant phenotype in OMIM (MIM# 158000) and G2P with a 'definitive' disease confidence classification. Monoallelic variant have been linked to monilethrix and multiple (>3) families have been reported in the literature. Overall there is enough evidence to promote this gene to Green at the next GMS panel update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v3.16 | KRT83 | Arina Puzriakova Phenotypes for gene: KRT83 were changed from to Monilethrix, OMIM:158000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v3.15 | KRT81 | Arina Puzriakova Phenotypes for gene: KRT81 were changed from to Monilethrix, OMIM:158000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v3.14 | KRT86 | Arina Puzriakova Phenotypes for gene: KRT86 were changed from Monilethrix to Monilethrix, OMIM:158000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v3.8 | KRT81 | Ronnie Wright reviewed gene: KRT81: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 9665406, 9402962; Phenotypes: Monilethrix; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v3.8 | KRT83 | Ronnie Wright reviewed gene: KRT83: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 15744029, 25557232; Phenotypes: Monilethrix; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v3.8 | KRT86 |
Ronnie Wright gene: KRT86 was added gene: KRT86 was added to Ectodermal dysplasia. Sources: NHS GMS Mode of inheritance for gene: KRT86 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KRT86 were set to PMID: 10469314; 10594761; 10504448; 12653715 Phenotypes for gene: KRT86 were set to Monilethrix Penetrance for gene: KRT86 were set to Incomplete Review for gene: KRT86 was set to GREEN Added comment: We've had clinician enquiries in North West GLH about Keratin Genes associated with Monilethrix (see also KRT81 and KRT83) not being present in Ectodermal dysplasia panel. It may be worth reviewing the evidence for all 3 of these genes. There are few publications for KRT81 and KRT83 but I think there are sufficient for KRT86 and for all 3 genes the reported variants seem to be consistent with pathogenic enriched regions in Keratin genes (see PER viewer for whole Keratin gene family https://per.broadinstitute.org/). Sources: NHS GMS |
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| Ectodermal dysplasia v3.3 | TUFT1 | Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER despite having three unrelated cases, as the variant found in two families is a founder variant in the Irish population. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v3.2 | TUFT1 |
Achchuthan Shanmugasundram gene: TUFT1 was added gene: TUFT1 was added to Ectodermal dysplasia. Sources: Literature Mode of inheritance for gene: TUFT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TUFT1 were set to 36689522 Phenotypes for gene: TUFT1 were set to ectodermal dysplasia syndrome, MONDO:0019287 Review for gene: TUFT1 was set to AMBER Added comment: PMID:36689522 reported nine individuals from three different families with biallelic variants in TUFT1 gene and presenting with woolly hair and skin fragility. One donor splice-site variant, c.60+1G>A, was present in two families, while a frameshift variant, p.Gln189Asnfs*49, was found in the third family. Haplotype analysis showed the c.60+1G>A variant is a founder variant in the Irish population. This is also supported by functional studies, mainly expression studies. This gene has not yet been associated with any phenotypes in OMIM or in Gene2Phenotype. Sources: Literature |
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| Ectodermal dysplasia v2.5 | HR | Arina Puzriakova Tag Q1_22_MOI was removed from gene: HR. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v2.5 | HR | Arina Puzriakova commented on gene: HR: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v2.4 | HR |
Arina Puzriakova Source NHS GMS was added to HR. Mode of inheritance for gene HR was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Ectodermal dysplasia v2.2 | SREBF1 |
Achchuthan Shanmugasundram gene: SREBF1 was added gene: SREBF1 was added to Ectodermal dysplasia. Sources: Literature Mode of inheritance for gene: SREBF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SREBF1 were set to 31790666; 32497488; 32902915; 33253727; 33742461 Phenotypes for gene: SREBF1 were set to Ichthyosis, follicular, with atrichia and photophobia syndrome 2, MIM# 619016, MONDO:0100221; Mucoepithelial dysplasia, hereditary, MIM# 158310, MONDO:0008017 Review for gene: SREBF1 was set to GREEN Added comment: Comment on classification of this gene: The rating for this gene should be added as GREEN, as this gene has been implicated in both hereditary hair and skin conditions, as identified from monoallelic variants from at least 18 unrelated individuals/ families from multiple ethnicities, and supported by results from in vitro functional studies. As reviewed by Zornitza Stark, heterozygous variants in 11 unrelated, ethnically diverse individuals has resulted in IFAP syndrome (MIM# 619016), which is characterised generally by moderate or severe hypotrichosis or atrichia (hair), ichthyosis follicularis (skin), and photophobia, Meibomian gland dysfunction, keratitis and/or cataract (eye) (PMID:32497488). Similarly, autosomal-dominant IFAP syndrome was also observed in another report of a Japanese woman and her daughter displaying heterozygous variant c.1669C>T (p.Arg557Cys) in SREBF1 gene (PMID:33253727). Seven patients from four families displaying heterozygous variants of SREBF1 gene (c.1669C>T (p.Arg557Cys) and c.1670G>A (p.Arg557His)) were reported with HMD (MIM# 158310), which is characterised by chronic keratitis, non-scarring alopecia, mucosal erythema, keratosis pilaris, perineal erythematous intertrigo, psoriatic-like perineal plaques, and involvement of the conjunctival mucosa (PMID:31790666). There are also two other reports of patients with c.1669C>T (p.Arg557Cys) variant displaying autosomal-dominant HMD (PMID:32902915, PMID:33742461). The clinical indications of IFAP and HMD suggests that these two diseases share a common clinical spectrum. The association of both IFAP and HMD to SREBF1 has been documented in OMIM. In addition, results from in vitro investigation of SREBP1 variants confirms the essential role of SREBF1 in epidermal differentiation, skin barrier formation, hair growth, and eye function (PMID:32497488). Sources: Literature |
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| Ectodermal dysplasia v1.33 | HR | Arina Puzriakova Publications for gene: HR were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v1.32 | HR | Arina Puzriakova Phenotypes for gene: HR were changed from HYPT4; Marie Unna hereditary hypotrichosis 1 (MUHH1); Marie Unna hereditary hypotrichosis (MUHH); Hypotrichosis 4, 146550 to Marie Unna hereditary hypotrichosis (MUHH); Alopecia universalis, OMIM:203655; Atrichia with papular lesions, OMIM:209500 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v1.31 | HR | Arina Puzriakova Tag Q1_22_MOI tag was added to gene: HR. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v1.31 | HR | Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be updated from 'monoallelic' to 'both mono- and biallelic'. Heterozygous variants in the 5'UTR of HR have been shown to cause Marie Unna hereditary hypotrichosis while homozygous variants have been associated with Alopecia universalis (MIM# 203655) and Atrichia with papular lesions (MIM# 209500), therefore both inheritance patterns are relevant to this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v1.31 | HR | Arina Puzriakova Mode of inheritance for gene: HR was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v1.7 | PRKD1 |
Arina Puzriakova gene: PRKD1 was added gene: PRKD1 was added to Ectodermal dysplasia. Sources: Literature for-review tags were added to gene: PRKD1. Mode of inheritance for gene: PRKD1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: PRKD1 were set to 27479907; 32817298 Phenotypes for gene: PRKD1 were set to Congenital heart defects and ectodermal dysplasia, 617364 Review for gene: PRKD1 was set to GREEN Added comment: PMID: 27479907 (2016) - Three unrelated cases with de novo missense variants in the PRKD1 gene. Variable characteristics of ectodermal dysplasia included sparse hair, dry or thin skin, fragile nails, and dental abnormalities (premature loss of primary teeth, small widely spaced teeth). Additional features include atrioventricular septal defects or pulmonic stenosis, severe developmental delay and microcephaly. No functional studies of the variants were performed. PMID: 32817298 (2020) - Two additional unrelated cases with de novo variants, c.1774G>C and c.1808G>A, respectively. Both displayed features of ectodermal dysplasia such as dry skin, absence of permanent teeth and poor hair growth. Other features included congenital heart defects, skeletal abnormalities and generalised teleangiectasia. Sources: Literature |
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| Ectodermal dysplasia v0.34 | KRT83 |
Catherine Snow changed review comment from: KRT81 is in OMIM with relevant phenotype of Monilethrix, KRT81 is part of a family of genes with KRT86 and KRT83 with this phenotype. Less than three individuals identified in KRT83 with phenotype of Monilethrix. In OMIM in a monoallelic form KRT83 variant has been reported in one Pakistani kindred, associated with Erythrokeratodermia variabilis et progressiva, all family members had normal hair, teeth, and sweating therefore different phenotype. As neither phenotype has more than three variants identified KRT83 will be classified as Amber.; to: KRT83 is in OMIM with relevant phenotype of Monilethrix, KRT83 is part of a family of genes with KRT86 and KRT81 with this phenotype. Less than three individuals identified in KRT83 with phenotype of Monilethrix. In OMIM in a monoallelic form KRT83 variant has been reported in one Pakistani kindred, associated with Erythrokeratodermia variabilis et progressiva, all family members had normal hair, teeth, and sweating therefore different phenotype. As neither phenotype has more than three variants identified KRT83 will be classified as Amber. |
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| Ectodermal dysplasia v0.34 | KRT83 |
Catherine Snow edited their review of gene: KRT83: Added comment: KRT81 is in OMIM with relevant phenotype of Monilethrix, KRT81 is part of a family of genes with KRT86 and KRT83 with this phenotype. Less than three individuals identified in KRT83 with phenotype of Monilethrix. In OMIM in a monoallelic form KRT83 variant has been reported in one Pakistani kindred, associated with Erythrokeratodermia variabilis et progressiva, all family members had normal hair, teeth, and sweating therefore different phenotype. As neither phenotype has more than three variants identified KRT83 will be classified as Amber.; Changed phenotypes: Monilethrix, 158000, Erythrokeratodermia variabilis et progressiva, 617756; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Ectodermal dysplasia v0.34 | KRT81 | Catherine Snow changed review comment from: KRT81 is in OMIM with relevant phenotype of Monilethrix. Two publications detailing two separate families, which reported that penetrance is variable and one family member had the variant but no reported symptoms. KRT81 currently classified as Amber as less than 3 unrelated individuals identified.; to: KRT81 is in OMIM with relevant phenotype of Monilethrix. Two publications detailing two separate families, which reported that penetrance is variable and one family member had the variant but no reported symptoms, therefore classifying KRT81 as Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v0.33 | KRT81 | Catherine Snow edited their review of gene: KRT81: Added comment: KRT81 is in OMIM with relevant phenotype of Monilethrix. Two publications detailing two separate families, which reported that penetrance is variable and one family member had the variant but no reported symptoms. KRT81 currently classified as Amber as less than 3 unrelated individuals identified.; Changed publications: 9402962, 9665406; Changed phenotypes: Monilethrix | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v0.17 | WNT7A | Catherine Snow Phenotypes for gene: WNT7A were changed from to Fuhrmann syndrome, 228930 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v0.3 | WDR19 |
Ellen McDonagh gene: WDR19 was added gene: WDR19 was added to Ectodermal dysplasia. Sources: Expert Review Red Mode of inheritance for gene: WDR19 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: WDR19 were set to Cranioectodermal dysplasia 4, 614378; Cranioectodermal Dysplasia; Asphyxiating thoracic dystrophy 5, 614376; Nephronophthisis 13, 614377 |
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| Ectodermal dysplasia v0.3 | HR |
Ellen McDonagh gene: HR was added gene: HR was added to Ectodermal dysplasia. Sources: Expert Review Green Mode of inheritance for gene: HR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: HR were set to HYPT4; Marie Unna hereditary hypotrichosis 1 (MUHH1); Marie Unna hereditary hypotrichosis (MUHH); Hypotrichosis 4, 146550 Mode of pathogenicity for gene: HR was set to Other - please provide details in the comments |
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| Ectodermal dysplasia v0.3 | DSC3 |
Ellen McDonagh gene: DSC3 was added gene: DSC3 was added to Ectodermal dysplasia. Sources: Expert Review Red Mode of inheritance for gene: DSC3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DSC3 were set to 19765682 Phenotypes for gene: DSC3 were set to hypotrichosis and recurrent skin vesicles disorder, 613102; HRSV; ?Hypotrichosis and recurrent skin vesicles, 613102 |
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| Ectodermal dysplasia v0.3 | CYBB |
Ellen McDonagh gene: CYBB was added gene: CYBB was added to Ectodermal dysplasia. Sources: Expert Review Red Mode of inheritance for gene: CYBB was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: CYBB were set to CGD; Chronic granulomatous disease, X-linked, 306400; discoid lupus erythematosus |
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