Activity

Filter

Cancel
Date Panel Item Activity
24 actions
Retinal disorders v9.4 COL11A1 Ida Ertmanska changed review comment from: PMID: 32578940 Nixon et al., 2020
Female patient with clinical type 2 Stickler syndrome but with severe hearing loss and severe ocular features including retinal atrophy and retinal tears in childhood. She was comp het for COL11A1 variants: a de novo in frame deletion of COL11A1 (c.4109_4126del) and splice variant c.1245+2T>C which affects splicing of exon 9 (inherited from unaffected mother).
Her parents were nonconsanguineous and had no eye, hearing, joint, or palate abnormalities.
Author explanation of inheritance: "The de novo deletion alone would be expected to result in dominant type 2 Stickler syndrome, but missplicing of exon 9 leads to additional severe hearing loss."
"While exon 9 is expressed in both vitreous and immature chondrocytes, it is not expressed in mature chondrocytes" - so any variants affecting exon 9 do not cause fibrochondrogenesis, but a Stickler syndrome phenotype with severe hearing loss.

PMID: 31833174 Abreu et al., 2020
3yo male proband with pontocerebellar hypoplasia caused by a homozygous AMPD2 p.[Pro734Leu] variant, and Stickler syndrome 2, likely caused by a homozygous COL11A1 c.1168G > T, p.[Glu390Ter] change. He presented with high myopia, mild-to-moderate hearing loss, as well as AMPD2-related profound motor and language delay.

PMID: 23922384 Richards et al., 2013
3 families with recessive form of type 2 Stickler syndrome characterised by particularly profound hearing loss. Heterozygous parents either had minor signs associated with Stickler syndrome, or were asymptomatic.
F1 - proband with cleft palate, hypermetropia, and profound deafness, was comp het for COL11A1 variants: (c.1191delT, p.Asn398Metfs*19) and (c.4259G>T, p.Gly1420Val) - exon 9 and 58, respectively. Age-compatible hearing loss in the mother, and mild-to-moderate hearing loss in the father
F2 - proband with high myopia, Pierre Robin sequence, and profound hearing loss, similarly affected sibling. Comp het for COL11A1 c.1421dupC, p.Gly475Argfs*9 in exon 13 and c.991-24A>G in intron 8 - creating an alternative exon 9 acceptor splice site.
F3 - girl with hearing loss diagnosed at 5 weeks, and retinal dystrophy noted at 2 yrs, also had clinical joint laxity. Parents unaffected, no hearing loss. Comp het c.2607A>G, p.Ala869Ala (shown to affect splicing) and c.5398G>T, p.Gly1800Cys.

PMID: 23026214 Alzahrani et al., 2012
6yo patient with homozygous exon 9 c.1191delT, p.(Asn398Metfs*19) variant in COL11A1; phenotype: unilateral retinal detachment, SNHL, cleft palate, flat midface, micrognathia. Parents unaffected, only mild myopia seen in the father.

PMID: 21035103 Tompson et al., 2010
2 individuals with Fibrochondrogenesis (severe skeletal dysplasia).
Family 1 - proband of European descent, comp het for COL11A1 variants c.1786dupG, (p.Ala596GlyfsX8), and c.3124G>A, (p.Gly1042Arg); presented with skeletal dysplasia (no note of hearing assessment); mother had myopia and normal hearing, father had hearing loss and wore glasses since childhood.
Family 2 - male proband (European and African American descent) comp het for COL11A1 c.2386G>C (p.Gly796Arg) and c.3943G>T, (p.Gly1315X) variants; he has fibrochondrogenesis, mild-moderate hearing loss, high myopia and left cataract. Father had mild hearing loss, mother - mild myopia (normal hearing), otherwise asymptomatic.
Authors pose that LOF variants lead to dominant hearing loss.; to: PMID: 32578940 Nixon et al., 2020
Female patient with clinical type 2 Stickler syndrome but with severe hearing loss and severe ocular features including retinal atrophy and retinal tears in childhood. She was comp het for COL11A1 variants: a de novo in frame deletion of COL11A1 (c.4109_4126del) and splice variant c.1245+2T>C which affects splicing of exon 9 (inherited from unaffected mother).
Her parents were nonconsanguineous and had no eye, hearing, joint, or palate abnormalities.
Author explanation of inheritance: "The de novo deletion alone would be expected to result in dominant type 2 Stickler syndrome, but missplicing of exon 9 leads to additional severe hearing loss."
"While exon 9 is expressed in both vitreous and immature chondrocytes, it is not expressed in mature chondrocytes" - so any variants affecting exon 9 do not cause fibrochondrogenesis, but a Stickler syndrome phenotype with severe hearing loss.

PMID: 31833174 Abreu et al., 2020
3yo male proband with pontocerebellar hypoplasia caused by a homozygous AMPD2 p.[Pro734Leu] variant, and Stickler syndrome 2, likely caused by a homozygous COL11A1 c.1168G > T, p.[Glu390Ter] change. He presented with high myopia, mild-to-moderate hearing loss, as well as AMPD2-related profound motor and language delay.

PMID: 23922384 Richards et al., 2013
3 families with recessive form of type 2 Stickler syndrome characterised by particularly profound hearing loss. Heterozygous parents either had minor signs associated with Stickler syndrome, or were asymptomatic.
F1 - proband with cleft palate, hypermetropia, and profound deafness, was comp het for COL11A1 variants: (c.1191delT, p.Asn398Metfs*19) and (c.4259G>T, p.Gly1420Val) - exon 9 and 58, respectively. Age-compatible hearing loss in the mother, and mild-to-moderate hearing loss in the father
F2 - proband with high myopia, Pierre Robin sequence, and profound hearing loss, similarly affected sibling. Comp het for COL11A1 c.1421dupC, p.Gly475Argfs*9 in exon 13 and c.991-24A>G in intron 8 - creating an alternative exon 9 acceptor splice site.
F3 - girl with hearing loss diagnosed at 5 weeks, and retinal dystrophy noted at 2 yrs, also had clinical joint laxity. Parents unaffected, no hearing loss. Comp het c.2607A>G, p.Ala869Ala (shown to affect splicing) and c.5398G>T, p.Gly1800Cys.

PMID: 23026214 Alzahrani et al., 2012
6yo patient with homozygous exon 9 c.1191delT, p.(Asn398Metfs*19) variant in COL11A1; phenotype: unilateral retinal detachment, SNHL, cleft palate, flat midface, micrognathia. Parents unaffected, only mild myopia seen in the father.

PMID: 21035103 Tompson et al., 2010
2 individuals with Fibrochondrogenesis (severe skeletal dysplasia).
Family 1 - proband of European descent, comp het for COL11A1 variants c.1786dupG, (p.Ala596GlyfsX8), and c.3124G>A, (p.Gly1042Arg); presented with skeletal dysplasia (no note of hearing assessment); mother had myopia and normal hearing, father had hearing loss and wore glasses since childhood.
Family 2 - male proband (European and African American descent) comp het for COL11A1 c.2386G>C (p.Gly796Arg) and c.3943G>T, (p.Gly1315X) variants; he has fibrochondrogenesis, mild-moderate hearing loss, high myopia and left cataract. Father had mild hearing loss, mother - mild myopia (normal hearing), otherwise asymptomatic. Authors pose that LOF variants lead to dominant hearing loss.
Retinal disorders v9.4 COL11A1 Ida Ertmanska changed review comment from: Comment on mode of inheritance: While heterozygous LOF variants in COL11A1 are known to cause dominant Stickler syndrome, there are also more than 3 unrelated cases reported with biallelic COL11A1 variants and Stickler syndrome with more severe presentation. Variabel reported ocular features included retinal atrophy, retinal tears, high myopia, unilateral retinal detachment, hypermetropia, and cataract. These cases did not present with skeletal dysplasia, as they had variants in alternatively spliced exon 9 on one or both alleles (exon 9 is not expressed in mature chondrocytes). Heterozygous parents of these individuals were either asymptomatic, or had mild myopia / mild hearing loss. Hence, the MOI should be changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.; to: Comment on mode of inheritance: While heterozygous LOF variants in COL11A1 are known to cause dominant Stickler syndrome / Marshall syndrome / isolated hearing loss, there are also more than 3 unrelated cases reported with biallelic COL11A1 variants and Stickler syndrome with more severe presentation. Variable reported ocular features included retinal atrophy, retinal tears, high myopia, unilateral retinal detachment, hypermetropia, and cataract. These cases did not present with skeletal dysplasia, as they had variants in alternatively spliced exon 9 on one or both alleles (exon 9 is not expressed in mature chondrocytes). Heterozygous parents of these individuals were either asymptomatic, or had mild myopia / mild hearing loss. Hence, the MOI should be changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Retinal disorders v9.4 COL11A1 Ida Ertmanska Publications for gene: COL11A1 were set to 10486316; 17318849
Retinal disorders v9.3 COL11A1 Ida Ertmanska Tag Q2_26_MOI tag was added to gene: COL11A1.
Retinal disorders v9.3 COL11A1 Ida Ertmanska changed review comment from: Comment on mode of inheritance: While heterozygous LOF variants in COL11A1 are known to cause dominant Stickler syndrome, there are also more than 3 unrelated cases reported with biallelic COL11A1 variants and Stickler syndrome with more severe presentation. Variabel reported ocular features included retinal atrophy, retinal tears, high myopia, unilateral retinal detachment, hypermetropia, and cataract. These cases did not present with skeletal dysplasia, as they had variants in alternatively spliced exon 9 on one or both alleles (exon 9 is not expressed in mature chondrocytes). Heterozygous parents of these individuals were either asymptomatic, or had mild myopia / mild hearing loss. Hence, the MOI should be changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal.; to: Comment on mode of inheritance: While heterozygous LOF variants in COL11A1 are known to cause dominant Stickler syndrome, there are also more than 3 unrelated cases reported with biallelic COL11A1 variants and Stickler syndrome with more severe presentation. Variabel reported ocular features included retinal atrophy, retinal tears, high myopia, unilateral retinal detachment, hypermetropia, and cataract. These cases did not present with skeletal dysplasia, as they had variants in alternatively spliced exon 9 on one or both alleles (exon 9 is not expressed in mature chondrocytes). Heterozygous parents of these individuals were either asymptomatic, or had mild myopia / mild hearing loss. Hence, the MOI should be changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Retinal disorders v9.3 COL11A1 Ida Ertmanska commented on gene: COL11A1: Comment on mode of inheritance: While heterozygous LOF variants in COL11A1 are known to cause dominant Stickler syndrome, there are also more than 3 unrelated cases reported with biallelic COL11A1 variants and Stickler syndrome with more severe presentation. Variabel reported ocular features included retinal atrophy, retinal tears, high myopia, unilateral retinal detachment, hypermetropia, and cataract. These cases did not present with skeletal dysplasia, as they had variants in alternatively spliced exon 9 on one or both alleles (exon 9 is not expressed in mature chondrocytes). Heterozygous parents of these individuals were either asymptomatic, or had mild myopia / mild hearing loss. Hence, the MOI should be changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal.
Retinal disorders v9.3 COL11A1 Ida Ertmanska reviewed gene: COL11A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32578940, 31833174, 23922384, 23026214, 21035103; Phenotypes: Deafness, autosomal dominant 37, 618533, Marshall syndrome, 154780, Stickler syndrome, type II, 604841, Fibrochondrogenesis 1, 228520; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Retinal disorders v3.30 COL11A1 Achchuthan Shanmugasundram Classified gene: COL11A1 as Green List (high evidence)
Retinal disorders v3.30 COL11A1 Achchuthan Shanmugasundram Gene: col11a1 has been classified as Green List (High Evidence).
Retinal disorders v3.29 COL11A1 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: COL11A1.
Tag Q1_23_promote_green was removed from gene: COL11A1.
Tag Q1_23_expert_review was removed from gene: COL11A1.
Retinal disorders v3.29 COL11A1 Achchuthan Shanmugasundram edited their review of gene: COL11A1: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Retinal disorders v3.29 COL11A1 Achchuthan Shanmugasundram Deleted their comment
Retinal disorders v3.26 COL11A1 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE tag was added to gene: COL11A1.
Retinal disorders v3.26 COL11A1 Achchuthan Shanmugasundram commented on gene: COL11A1: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required before promoting this gene to green.
Retinal disorders v3.16 COL11A1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: COL11A1.
Tag Q1_23_expert_review tag was added to gene: COL11A1.
Retinal disorders v3.16 COL11A1 Achchuthan Shanmugasundram Phenotypes for gene: COL11A1 were changed from Stickler syndrome, type II, OMIM:604841 to Stickler syndrome, type II, OMIM:604841; Marshall syndrome, OMIM:154780
Retinal disorders v3.15 COL11A1 Achchuthan Shanmugasundram Publications for gene: COL11A1 were set to
Retinal disorders v3.14 COL11A1 Achchuthan Shanmugasundram Mode of inheritance for gene: COL11A1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Retinal disorders v3.13 COL11A1 Achchuthan Shanmugasundram reviewed gene: COL11A1: Rating: ; Mode of pathogenicity: None; Publications: 10486316, 17318849; Phenotypes: Marshall syndrome, OMIM:154780, Stickler syndrome, type II, OMIM:604841; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Retinal disorders v3.6 COL11A1 Eleanor Williams reviewed gene: COL11A1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Stickler syndrome, Marshall syndrome,, beaded vitreous, early onset hearing loss, retinal detachment; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Retinal disorders v2.223 COL11A1 Arina Puzriakova Phenotypes for gene: COL11A1 were changed from Eye Disorders to Stickler syndrome, type II, OMIM:604841
Retinal disorders v1.160 COL11A1 Ivone Leong reviewed gene: COL11A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v1.159 COL11A1 Gavin Arno reviewed gene: COL11A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v1.137 COL11A1 Ivone Leong Source NHS GMS was added to COL11A1.