Activity

Filter

Cancel
Date Panel Item Activity
26 actions
Pigmentary skin disorders v4.21 SNAI2 Achchuthan Shanmugasundram changed review comment from: PMID:12444107 (2002) reported the identification of homozygous deletions in SNAI2 gene (previous gene name: SLUG) in two unrelated patients with Waardenburg syndrome type 2 (WS2). The first patient was reported with profound bilateral sensorineural hearing loss and heterochromia iridis, while the second patient presented with 60 dB hearing loss and unilateral heterochromia. Neither of the patients were reported with any pigmentary abnormalities of the skin.

PMID:12955764 (2003) reported Southern blot analysis of the SNAI2 (SLUG) gene in 17 unrelated patients with piebaldism, who lacked apparent KIT mutations. Three patients had evident heterozygous deletions of the SNAI2 gene encompassing the entire coding region. However, Celia Moss (one of the co-authors of this publication) reviewed below that one of the reported patients was from her and it was identified from further investigation that this patient had a KIT mutation and not SNAI2.

PMID:24443330 (2014) reported a female patient of Chinese descent with a SNAI2 5'UTR variant and a recurrent EDA1 variant. The patient presented with a mild form of piebaldism and a severe form of X-linked hypohidrotic ectodermal dysplasia.

PMID:30936914 (2019) reported a 90-patient WS cohort from which two novel heterozygous variants in SNAI2 gene were identified in one patient each. One of these patients were reported with WS2 and other with WS4, and both presented with heterochromia irides and hearing loss. Both the detected SNAI2 variants (c.230C>G and c.365C>T) were not considered causative due to their frequency (>1/10000) in the population database.

PMID:41073431 (2025) reported a family of Chinese descent with WS and with a pathogenic heterozygous SNAI2 variant (c.230C>G). All four adolescents from the family (third generation) presented moderate to severe ID, along with severe anxiety, mild level of depression, and serious social dysfunction. But they did not show any signs of hearing loss and heterochromia iris, which are considered features of WS.

This gene has not yet been associated with any relevant phenotypes in OMIM (last accessed 29 April 2026), but recessive variants are associated with 'limited' rating by Hearing Loss GCEP in ClinGen.; to: PMID:12444107 (2002) reported the identification of homozygous deletions in SNAI2 gene (previous gene name: SLUG) in two unrelated patients with Waardenburg syndrome type 2 (WS2). The first patient was reported with profound bilateral sensorineural hearing loss and heterochromia iridis, while the second patient presented with 60 dB hearing loss and unilateral heterochromia. Neither of the patients were reported with any pigmentary abnormalities of the skin.

PMID:12955764 (2003) reported Southern blot analysis of the SNAI2 (SLUG) gene in 17 unrelated patients with piebaldism, who lacked apparent KIT mutations. Three patients had evident heterozygous deletions of the SNAI2 gene encompassing the entire coding region. However, Celia Moss (one of the co-authors of this publication) reviewed below that one of the reported patients was from her and it was identified from further investigation that this patient had a KIT mutation and not SNAI2.

PMID:24443330 (2014) reported a female patient of Chinese descent with a SNAI2 5'UTR variant and a recurrent EDA1 variant. The patient presented with a mild form of piebaldism and a severe form of X-linked hypohidrotic ectodermal dysplasia.

PMID:30936914 (2019) reported a 90-patient WS cohort from which two novel heterozygous variants in SNAI2 gene were identified in one patient each. One of these patients were reported with WS2 and other with WS4, and both presented with heterochromia irides and hearing loss. Both the detected SNAI2 variants (c.230C>G and c.365C>T) were not considered causative due to their frequency (>1/10000) in the population database.

PMID:41073431 (2025) reported a family of Chinese descent with WS and with a pathogenic heterozygous SNAI2 variant (c.230C>G). All four adolescents from the family (third generation) presented moderate to severe ID, along with severe anxiety, mild level of depression, and serious social dysfunction. But they did not show any signs of hearing loss or heterochromia iris, which are considered features of WS.

This gene has not yet been associated with any relevant phenotypes in OMIM (last accessed 29 April 2026), but recessive variants are associated with 'limited' rating by Hearing Loss GCEP in ClinGen.
Pigmentary skin disorders v4.21 SNAI2 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There are three unrelated patients reported with monoallelic SNAI2 variants (excluding the family from Celia Moss, who has later been identified with KIT variant) and piebaldism (mild in the patient reported in PMID:24443330, who also had EDA1 variant). However, all three families reported with heterozygous variants in the recent literature (PMIDs: 30936914; 41073431) presented with Waardenburg syndrome (variants from two cases from PMID:30936914 had higher frequencies in population databases) and did not have any phenotype relevant to pigmentary skin disorders.

There are two unrelated patients reported with homozygous SNAI2 deletions and with Waardenburg syndrome. These patients presented with hearing loss and heterochromia iridis and not with any skin pigmentation phenotypes.

The MOI should therefore be updated from 'BIALLELIC, autosomal or pseudoautosomal' to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' as the patients with biallelic variants did not present with any skin pigmentation phenotypes.

The rating should remain amber as none of the recent monoallelic cases had piebaldism and the earlier cases with piebaldism were identified with SNAI2 deletion/variants via Southern blots/ single gene sequencing. The 'watchlist' tag has been added for reviewing this gene with new evidence in the future.
Pigmentary skin disorders v4.18 SNAI2 Achchuthan Shanmugasundram changed review comment from: PMID:12444107 (2002) reported the identification of homozygous deletions in SNAI2 gene (previous gene name: SLUG) in two unrelated patients with Waardenburg syndrome type 2 (WS2). The first patient was reported with profound bilateral sensorineural hearing loss and heterochromia iridis, while the second patient presented with 60 dB hearing loss and unilateral heterochromia. Neither of the patients were reported with any pigmentary abnormalities of the skin.

PMID:12955764 (2003) reported Southern blot analysis of the SNAI2 (SLUG) gene in 17 unrelated patients with piebaldism, who lacked apparent KIT mutations. Three patients had evident heterozygous deletions of the SNAI2 gene encompassing the entire coding region. However, Celia Moss (one of the co-authors of this publication) reviewed below that one of the reported patients was from her and it was identified from further investigation that this patient had a KIT mutation and not SNAI2.

PMID:24443330 (2014) reported a female patient of Chinese descent with a SNAI2 5'UTR variant and a recurrent EDA1 variant. The patient presented with a mild form of piebaldism and a severe form of X-linked hypohidrotic ectodermal dysplasia.

PMID:30936914 (2019) reported a 90-patient WS cohort from which two novel heterozygous variants in SNAI2 gene were identified in one patient each. Both the detected SNAI2 variants (c.230C>G and c.365C>T) were not considered causative due to their frequency (>1/10000) in the population database.

PMID:41073431 (2025) reported a family of Chinese descent with WS and with a pathogenic heterozygous SNAI2 variant (c.230C>G). All four adolescents from the family (third generation) presented moderate to severe ID, along with severe anxiety, mild level of depression, and serious social dysfunction. But they did not show any signs of hearing loss and heterochromia iris, which are considered features of WS.

This gene has not yet been associated with any relevant phenotypes in OMIM (last accessed 29 April 2026), but recessive variants are associated with 'limited' rating by Hearing Loss GCEP in ClinGen.; to: PMID:12444107 (2002) reported the identification of homozygous deletions in SNAI2 gene (previous gene name: SLUG) in two unrelated patients with Waardenburg syndrome type 2 (WS2). The first patient was reported with profound bilateral sensorineural hearing loss and heterochromia iridis, while the second patient presented with 60 dB hearing loss and unilateral heterochromia. Neither of the patients were reported with any pigmentary abnormalities of the skin.

PMID:12955764 (2003) reported Southern blot analysis of the SNAI2 (SLUG) gene in 17 unrelated patients with piebaldism, who lacked apparent KIT mutations. Three patients had evident heterozygous deletions of the SNAI2 gene encompassing the entire coding region. However, Celia Moss (one of the co-authors of this publication) reviewed below that one of the reported patients was from her and it was identified from further investigation that this patient had a KIT mutation and not SNAI2.

PMID:24443330 (2014) reported a female patient of Chinese descent with a SNAI2 5'UTR variant and a recurrent EDA1 variant. The patient presented with a mild form of piebaldism and a severe form of X-linked hypohidrotic ectodermal dysplasia.

PMID:30936914 (2019) reported a 90-patient WS cohort from which two novel heterozygous variants in SNAI2 gene were identified in one patient each. One of these patients were reported with WS2 and other with WS4, and both presented with heterochromia irides and hearing loss. Both the detected SNAI2 variants (c.230C>G and c.365C>T) were not considered causative due to their frequency (>1/10000) in the population database.

PMID:41073431 (2025) reported a family of Chinese descent with WS and with a pathogenic heterozygous SNAI2 variant (c.230C>G). All four adolescents from the family (third generation) presented moderate to severe ID, along with severe anxiety, mild level of depression, and serious social dysfunction. But they did not show any signs of hearing loss and heterochromia iris, which are considered features of WS.

This gene has not yet been associated with any relevant phenotypes in OMIM (last accessed 29 April 2026), but recessive variants are associated with 'limited' rating by Hearing Loss GCEP in ClinGen.
Pigmentary skin disorders v3.2 KITLG Arina Puzriakova Phenotypes for gene: KITLG were changed from HYPERPIGMENTATION WITH OR WITHOUT HYPOPIGMENTATION, FAMILIAL PROGRESSIVE; Progressive hyper-and hypopigmentation; Blaschko-linear hypopigmentation; FPHH to Hyperpigmentation with or without hypopigmentation, OMIM:145250; Progressive hyper-and hypopigmentation; Blaschko-linear hypopigmentation; FPHH
Pigmentary skin disorders v2.3 KIT Arina Puzriakova Tag Q1_22_MOI was removed from gene: KIT.
Pigmentary skin disorders v2.3 KIT Arina Puzriakova commented on gene: KIT: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Pigmentary skin disorders v2.2 KIT Arina Puzriakova Mode of inheritance for gene KIT was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Pigmentary skin disorders v1.40 KIT Arina Puzriakova Tag Q1_22_MOI tag was added to gene: KIT.
Pigmentary skin disorders v1.40 KIT Arina Puzriakova Publications for gene: KIT were set to 9990072; 1370874
Pigmentary skin disorders v1.39 KIT Arina Puzriakova Phenotypes for gene: KIT were changed from PBT; Piebaldism; MASTC, PIEBALD TRAIT; Mast cell disease; MASTOCYTOSIS, CUTANEOUS to Mastocytosis, cutaneous, OMIM:154800; Piebaldism, OMIM:172800
Pigmentary skin disorders v1.38 KIT Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be be updated from 'monoallelic' to 'both mono- and biallelic (but biallelic mutations cause a more SEVERE disease form)' (tagged)

Copied from Ellen McDonagh (Genomics England Curator) review on Hearing loss panel:
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.
Pigmentary skin disorders v1.38 KIT Arina Puzriakova Mode of inheritance for gene: KIT was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pigmentary skin disorders v0.27 KITLG Catherine Snow Added phenotypes HYPERPIGMENTATION WITH OR WITHOUT HYPOPIGMENTATION, FAMILIAL PROGRESSIVE; FPHH for gene: KITLG
Publications for gene KITLG were changed from to 21368769
Pigmentary skin disorders v0.27 KIT Catherine Snow Added phenotypes PBT; MASTOCYTOSIS, CUTANEOUS; MASTC, PIEBALD TRAIT for gene: KIT
Publications for gene KIT were changed from to 9990072; 1370874
Pigmentary skin disorders v0.27 ADAM10 Catherine Snow Added phenotypes Reticulate acropigmentation of Kitamura for gene: ADAM10
Publications for gene ADAM10 were changed from to 23666529
Pigmentary skin disorders v0.25 KITLG Tom Cullup reviewed gene: KITLG: Rating: GREEN; Mode of pathogenicity: ; Publications: 21368769; Phenotypes: HYPERPIGMENTATION WITH OR WITHOUT HYPOPIGMENTATION, FAMILIAL PROGRESSIVE, FPHH; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pigmentary skin disorders v0.25 KIT Tom Cullup reviewed gene: KIT: Rating: GREEN; Mode of pathogenicity: ; Publications: 1370874, 9990072; Phenotypes: MASTOCYTOSIS, CUTANEOUS, MASTC, PIEBALD TRAIT, PBT; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pigmentary skin disorders v0.25 ADAM10 Tom Cullup reviewed gene: ADAM10: Rating: GREEN; Mode of pathogenicity: ; Publications: 23666529; Phenotypes: Reticulate acropigmentation of Kitamura; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pigmentary skin disorders v0.8 KIT Anna de Burca reviewed gene: KIT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Piebaldism, Gastrointestinal stromal tumor, familial; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pigmentary skin disorders v0.8 KITLG Rebecca Foulger Source London North GLH was added to KITLG.
Pigmentary skin disorders v0.8 KIT Rebecca Foulger Source London North GLH was added to KIT.
Pigmentary skin disorders v0.4 KITLG Rebecca Foulger reviewed gene: KITLG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pigmentary skin disorders v0.4 KIT Rebecca Foulger reviewed gene: KIT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pigmentary skin disorders v0.3 KITLG Rebecca Foulger gene: KITLG was added
gene: KITLG was added to Pigmentary skin disorders. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: KITLG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KITLG were set to Progressive hyper-and hypopigmentation; Blaschko-linear hypopigmentation
Pigmentary skin disorders v0.3 KIT Rebecca Foulger gene: KIT was added
gene: KIT was added to Pigmentary skin disorders. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: KIT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KIT were set to Mast cell disease; Piebaldism
Pigmentary skin disorders v0.3 ADAM10 Rebecca Foulger gene: ADAM10 was added
gene: ADAM10 was added to Pigmentary skin disorders. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: ADAM10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ADAM10 were set to Reticulate acropigmentation of Kitamura