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Monogenic hearing loss v6.32 COL4A6 Ida Ertmanska changed review comment from: PMID: 41092388 Owrang et al., 2026
Study identified two families affected by multiple genetic disorders. The first family presented a missense COL4A6 variant (NM_033641.4: c.1480G>A p.(Gly494Arg)), accounting for hearing loss, while a likely pathogenic HEXA variant (NM_000520.6: c.902T>G p.(Met301Arg)) explained Tay-Sachs disease features.
The second family exhibited a synonymous COL4A6 variant (NM_033641.4: c.1767G>A p.(Pro589=)), leading to partial exon skipping and hearing loss, along with a pathogenic splice-site variant in DYM (NM_001353214.3: c.1125 + 1G>T p.?), causing the Dyggve-Melchior-Clausen disease.

PMID: 40928595 Jagannath et al., 2025
Family 4, Indian origin - male proband with sensorineural hearing loss and a hemizygous variant in COL4A6: c.227G > A (p.Gly76Glu).

PMID: 39272213 Feng et al., 2024
Individual 23 - male, Chinese, with congenital hearing loss (Profound, SNHL, Malformed cochlea; CI) - harboured a hemizygous COL4A6 variant c.1456G>A, p.G486S.

PMID: 33840813 O'Brien et al., 2022
Report of 2 unrelated families with male probands hemizygous for COL4A6 variants: NM_001287758.1: c.3272 G > C (p.Gly1091Ala) and c.951+1G>C. An in vitro minigene splicing assay revealed that c.951+1G>T leads to skipping of exon 15.
Both variants were inherited from heterozygous mothers. However, the molecular diagnosis is complicated by presence of GJB2 and GJB6 variants in the two kindreds, which are also likely to contribute to hearing loss.

Functional evidence: PMID: 33848312 Tang et al., 2021 - loss of Col4a6 gene expression in mice showed normal click ABR thresholds and normal cochlear formation - LOF variants unlikely to cause hearing loss

The gene is linked to ?Deafness, X-linked 6, OMIM:300914 (OMIM accessed 22nd July 2026). The association between COL4A6 and hearing loss, X-linked 6 was classified as Limited in ClinGen (Feb 2022, Hearing Loss GCEP).; to: PMID: 41092388 Owrang et al., 2026
Study identified two families affected by multiple genetic disorders. The first family presented a missense COL4A6 variant (NM_033641.4: c.1480G>A p.(Gly494Arg)), accounting for hearing loss, while a likely pathogenic HEXA variant (NM_000520.6: c.902T>G p.(Met301Arg)) explained Tay-Sachs disease features.
The second family exhibited a synonymous COL4A6 variant (NM_033641.4: c.1767G>A p.(Pro589=)), leading to partial exon skipping and hearing loss, along with a pathogenic splice-site variant in DYM (NM_001353214.3: c.1125 + 1G>T p.?), causing the Dyggve-Melchior-Clausen disease.

PMID: 40928595 Jagannath et al., 2025
Family 4, Indian origin - male proband with sensorineural hearing loss and a hemizygous variant in COL4A6: c.227G > A (p.Gly76Glu). Parents unaffected, not genotyped.

PMID: 39272213 Feng et al., 2024
Individual 23 - male, Chinese, with congenital hearing loss (Profound, SNHL, Malformed cochlea; CI) - harboured a hemizygous COL4A6 variant c.1456G>A, p.G486S.

PMID: 33840813 O'Brien et al., 2022
Report of 2 unrelated families with male probands hemizygous for COL4A6 variants: NM_001287758.1: c.3272 G > C (p.Gly1091Ala) and c.951+1G>C. An in vitro minigene splicing assay revealed that c.951+1G>T leads to skipping of exon 15.
Both variants were inherited from heterozygous affected mothers. However, the molecular diagnosis is complicated by presence of GJB2 and GJB6 variants in the two kindreds, which are also likely to contribute to hearing loss.

Functional evidence: PMID: 33848312 Tang et al., 2021 - loss of Col4a6 gene expression in mice showed normal click ABR thresholds and normal cochlear formation - LOF variants unlikely to cause hearing loss

The gene is linked to ?Deafness, X-linked 6, OMIM:300914 (OMIM accessed 22nd July 2026). The association between COL4A6 and hearing loss, X-linked 6 was classified as Limited in ClinGen (Feb 2022, Hearing Loss GCEP).
Monogenic hearing loss v6.30 COL4A6 Ida Ertmanska changed review comment from: PMID: 41092388 Owrang et al., 2026
Study identified two families affected by multiple genetic disorders. The first family presented a missense COL4A6 variant (NM_033641.4: c.1480G>A p.(Gly494Arg)), accounting for hearing loss, while a likely pathogenic HEXA variant (NM_000520.6: c.902T>G p.(Met301Arg)) explained Tay-Sachs disease features.
The second family exhibited a synonymous COL4A6 variant (NM_033641.4: c.1767G>A p.(Pro589=)), leading to partial exon skipping and hearing loss, along with a pathogenic splice-site variant in DYM (NM_001353214.3: c.1125 + 1G>T p.?), causing the Dyggve-Melchior-Clausen disease.

PMID: 40928595 Jagannath et al., 2025
Family 4, Indian origin - male proband with sensorineural hearing loss and a hemizygous variant in COL4A6: c.227G > A (p.Gly76Glu).

PMID: 39272213 Feng et al., 2024
Individual 23 - male, Chinese, with congenital hearing loss (Profound, SNHL, Malformed cochlea; CI) - harboured a hemizygous COL4A6 variant c.1456G>A, p.G486S.

PMID: 33840813 O'Brien et al., 2022
Report of 2 unrelated families with male probands hemizygous for COL4A6 variants: NM_001287758.1: c.3272 G > C (p.Gly1091Ala) and c.951+1G>C. An in vitro minigene splicing assay revealed that c.951+1G>T leads to skipping of exon 15.
Both variants were inherited from heterozygous mothers. However, the molecular diagnosis is complicated by presence of GJB2 and GJB6 variants in the two kindreds, which are also likely to contribute to hearing loss.

Functional evidence: PMID: 33848312 Tang et al., 2021 - loss of Col4a6 gene expression in mice showed normal click ABR thresholds and normal cochlear formation - LOF variants unlikely to cause hearing loss

The gene is linked to ?Deafness, X-linked 6, OMIM:300914 (OMIM accessed 22nd July 2026).; to: PMID: 41092388 Owrang et al., 2026
Study identified two families affected by multiple genetic disorders. The first family presented a missense COL4A6 variant (NM_033641.4: c.1480G>A p.(Gly494Arg)), accounting for hearing loss, while a likely pathogenic HEXA variant (NM_000520.6: c.902T>G p.(Met301Arg)) explained Tay-Sachs disease features.
The second family exhibited a synonymous COL4A6 variant (NM_033641.4: c.1767G>A p.(Pro589=)), leading to partial exon skipping and hearing loss, along with a pathogenic splice-site variant in DYM (NM_001353214.3: c.1125 + 1G>T p.?), causing the Dyggve-Melchior-Clausen disease.

PMID: 40928595 Jagannath et al., 2025
Family 4, Indian origin - male proband with sensorineural hearing loss and a hemizygous variant in COL4A6: c.227G > A (p.Gly76Glu).

PMID: 39272213 Feng et al., 2024
Individual 23 - male, Chinese, with congenital hearing loss (Profound, SNHL, Malformed cochlea; CI) - harboured a hemizygous COL4A6 variant c.1456G>A, p.G486S.

PMID: 33840813 O'Brien et al., 2022
Report of 2 unrelated families with male probands hemizygous for COL4A6 variants: NM_001287758.1: c.3272 G > C (p.Gly1091Ala) and c.951+1G>C. An in vitro minigene splicing assay revealed that c.951+1G>T leads to skipping of exon 15.
Both variants were inherited from heterozygous mothers. However, the molecular diagnosis is complicated by presence of GJB2 and GJB6 variants in the two kindreds, which are also likely to contribute to hearing loss.

Functional evidence: PMID: 33848312 Tang et al., 2021 - loss of Col4a6 gene expression in mice showed normal click ABR thresholds and normal cochlear formation - LOF variants unlikely to cause hearing loss

The gene is linked to ?Deafness, X-linked 6, OMIM:300914 (OMIM accessed 22nd July 2026). The association between COL4A6 and hearing loss, X-linked 6 was classified as Limited in ClinGen (Feb 2022, Hearing Loss GCEP).
Monogenic hearing loss v6.30 COL4A6 Ida Ertmanska changed review comment from: PMID: 41092388 Owrang et al., 2026
Study identified two families affected by multiple genetic disorders. The first family presented a missense COL4A6 variant (NM_033641.4: c.1480G>A p.(Gly494Arg)), accounting for hearing loss, while a likely pathogenic HEXA variant (NM_000520.6: c.902T>G p.(Met301Arg)) explained Tay-Sachs disease features.
The second family exhibited a synonymous COL4A6 variant (NM_033641.4: c.1767G>A p.(Pro589=)), leading to partial exon skipping and hearing loss, along with a pathogenic splice-site variant in DYM (NM_001353214.3: c.1125 + 1G>T p.?), causing the Dyggve-Melchior-Clausen disease.

PMID: 40928595 Jagannath et al., 2025
Family 4, Indian origin - male proband with sensorineural hearing loss and a hemizygous variant in COL4A6: c.227G > A (p.Gly76Glu).

PMID: 39272213 Feng et al., 2024
Individual 23 - male, Chinese, with congenital hearing loss (Profound, SNHL, Malformed cochlea; CI) - harboured a hemizygous COL4A6 variant c.1456G>A, p.G486S.

PMID: 33840813 O'Brien et al., 2022
Report of 2 unrelated families with male probands hemizygous for COL4A6 variants: NM_001287758.1: c.3272 G > C (p.Gly1091Ala) and c.951+1G>C. An in vitro minigene splicing assay revealed that c.951 + 1 G > T leads to skipping of exon 15.
Both variants were inherited from heterozygous mothers. However, the molecular diagnosis is complicated by presence of GJB2 and GJB6 varinats in the two kindreds, which are also likely to contribute to hearing loss.

The gene is linked to ?Deafness, X-linked 6, OMIM:300914 (OMIM accessed 22nd July 2026).; to: PMID: 41092388 Owrang et al., 2026
Study identified two families affected by multiple genetic disorders. The first family presented a missense COL4A6 variant (NM_033641.4: c.1480G>A p.(Gly494Arg)), accounting for hearing loss, while a likely pathogenic HEXA variant (NM_000520.6: c.902T>G p.(Met301Arg)) explained Tay-Sachs disease features.
The second family exhibited a synonymous COL4A6 variant (NM_033641.4: c.1767G>A p.(Pro589=)), leading to partial exon skipping and hearing loss, along with a pathogenic splice-site variant in DYM (NM_001353214.3: c.1125 + 1G>T p.?), causing the Dyggve-Melchior-Clausen disease.

PMID: 40928595 Jagannath et al., 2025
Family 4, Indian origin - male proband with sensorineural hearing loss and a hemizygous variant in COL4A6: c.227G > A (p.Gly76Glu).

PMID: 39272213 Feng et al., 2024
Individual 23 - male, Chinese, with congenital hearing loss (Profound, SNHL, Malformed cochlea; CI) - harboured a hemizygous COL4A6 variant c.1456G>A, p.G486S.

PMID: 33840813 O'Brien et al., 2022
Report of 2 unrelated families with male probands hemizygous for COL4A6 variants: NM_001287758.1: c.3272 G > C (p.Gly1091Ala) and c.951+1G>C. An in vitro minigene splicing assay revealed that c.951+1G>T leads to skipping of exon 15.
Both variants were inherited from heterozygous mothers. However, the molecular diagnosis is complicated by presence of GJB2 and GJB6 variants in the two kindreds, which are also likely to contribute to hearing loss.

Functional evidence: PMID: 33848312 Tang et al., 2021 - loss of Col4a6 gene expression in mice showed normal click ABR thresholds and normal cochlear formation - LOF variants unlikely to cause hearing loss

The gene is linked to ?Deafness, X-linked 6, OMIM:300914 (OMIM accessed 22nd July 2026).
Monogenic hearing loss v6.16 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" - apart from inner ear cartilage - 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.
Monogenic hearing loss v6.15 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 (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."

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 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, 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.
Monogenic hearing loss v6.15 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 (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."

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 c.1191delT, p.(Asn398Metfs*19) variant in COL11A1; phenotype: unilateral retinal detachment, SNHL, cleft palate, flat midface, micrognathia.

PMID: 21035103 Tompson et al., 2010
2 individuals with Fibrochondrogenesis (severe skeletal dysplasia).
Family 1 - proband, 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 (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."

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 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, 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.
Monogenic hearing loss v6.15 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.
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."

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.
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.; 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 (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."

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 c.1191delT, p.(Asn398Metfs*19) variant in COL11A1; phenotype: unilateral retinal detachment, SNHL, cleft palate, flat midface, micrognathia.

PMID: 21035103 Tompson et al., 2010
2 individuals with Fibrochondrogenesis (severe skeletal dysplasia).
Family 1 - proband, 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.