Monogenic hearing loss

Gene: COL11A1

Green List (high evidence)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 3 Mar 2022, 1:19 p.m. | Last Modified: 3 Mar 2022, 1:19 p.m.

Panel Version: 2.221

Comment on list classification: After consultation with the Genomics England clinical team it has been decided that this gene has sufficient cases with hearing loss to be promoted to green. Therefore this gene should be reviewed at the next GMS update.

Created: 24 Sep 2020, 6:40 p.m. | Last Modified: 24 Sep 2020, 6:40 p.m.

Panel Version: 2.94

PMID: 23967202 - Miyagawa et al 2013 - report 3 missense variants in Japanese hearing loss patients through targeted exome sequencing. 1 familial case shown with two affected siblings. They suggest the inheritance is autosomal dominant.

Created: 20 Sep 2020, 6:49 a.m. | Last Modified: 20 Sep 2020, 6:49 a.m.

Panel Version: 2.77

Comment on list classification: Promoting from red to amber. 1 case of non-syndromic hearing loss in a large pedigree. Other reports are from patients with Stickler/Marshal syndrome.

Created: 11 Sep 2020, 5:55 p.m. | Last Modified: 11 Sep 2020, 5:55 p.m.

Panel Version: 2.71

Associated with ?Deafness, autosomal dominant 37 #618533 (AD), Marshall syndrome #154780 and Stickler syndrome, type II #604841, and other phenotypes in OMIM.

PMID: 30245514 - Booth et al 2017 - report a four-generation family of European descent with post lingual progressive autosomal dominant nonsyndromic hearing loss. Exome sequencing identified an acceptor splice-site variant c.652-2A>C in the COL11A1 gene. This variant segregated with deafness in the 48 family members of the extended family who were tested.

PMID: 17236192 - Majava et al 2007 - report 10 patients with a normal COL2A1 screening result, whose phenotype was suggestive of either Stickler syndrome or Marshall syndrome and who were found to have heterozygous variants in COL11A1 (7 splice site mutations, 2 deletions, and 1 glycine substitution ). 6/10 had sensorineural hearing loss along with other features.

Created: 11 Sep 2020, 5:54 p.m. | Last Modified: 11 Sep 2020, 5:54 p.m.

Panel Version: 2.70

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Publications

• 30245514
• 17236192

Green List (high evidence)

Single family reported with isolated deafness and splicing variant in this gene; deafness can be a feature of Stickler syndrome. Stickler syndrome is relatively common; phenotypic variability can make clinical diagnosis difficult; early diagnosis and proactive management have the potential to alter visual outcomes.

Created: 29 Jan 2020, 12:18 a.m. | Last Modified: 29 Jan 2020, 12:18 a.m.

Panel Version: 2.4

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Stickler syndrome, type II, MIM#604841; Deafness, autosomal dominant 37, MIM#618533

Publications

• 30245514

Variants in this GENE are reported as part of current diagnostic practice

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
#154780:Marshall syndrome[Short stature; Flat midfaceMicrognathiaLong philtrum; Sensorineural hearing lossLow-set ears; MyopiaCongenital cataractsEsotropiaRetinal detachmentGlaucomaLens dislocationVitreoretinal degenerationHypertelorismEpicanthal folds; Short, depressed noseFlat nasal bridgeAnteverted nares; Thick lipsCleft palateRobin sequence; Prominent, protruding upper incisors; Calvarial thickeningAbsent frontal sinusesFalx, tentorial, and meningeal calcifications; Mild platyspondyly; Small iliac bonesCoxa valga; Small, irregular distal femoral epiphysesSmall, irregular proximal tibial epiphysesOutward radial bowingOutward ulnar bowing; Wide tufts of distal phalanges]; #228520:Fibrochondrogenesis 1[Short statureRhizomelic dwarfism; Large open anterior fontanelNormal head size; Round, flat faceLong philtrumFrontal bossing; Low-set earsMalformed ears; Protuberant eyesLarge corneae; Hypoplastic noseFlat nasal bridgeAnteverted nares; Cleft palateMicrostomia; Short neck; Patent foramen ovale; Small chest; Short, thin ribsAnterior and posterior rib cuppingLong, thin claviclesSmall scapulae; OmphaloceleProtuberant abdomen; Widely patent coronal sutureWidely patent sagittal suture; PlatyspondylyPosterior vertebral hypoplasiaSagittal cleft; Broad, hypoplastic ischiaOvoid iliaIrregular, flattened acetabula with medial spikesNarrow sacrosciatic notches; Rhizomelic limb shorteningShort, broad dumbbell-shaped tubular bones with irregular metaphysesShort fibulae; Small handsCamptodactylyFifth finger clinodactyly; Small feet; Hypoplastic fingernailsHypoplastic toenails; Hydrops; Stillborn; Disorganized growth plate cartilage]; #603932:{Lumbar disc herniation, susceptibility to}[<omim version=1.0><clinicalSynopsisList>]; #604841:Stickler syndrome, type II[Normal height; Flat midfaceMicrognathia; Sensorineural hearing loss; Myopia (onset before 6 years)CataractType 2 vitreous phenotype (irregularly thickened fiber bundles throughout vitreous cavity)GlaucomaRetinal detachment; Depressed nasal bridgeAnteverted nares; Cleft palatePierre-Robin sequenceBifid uvula; Mild spondyloepiphyseal dysplasia; Slender extremitiesJoint hypermobilityArthropathy (onset third-fourth decade); Long fingers]

Publications

• PMID:10486316
• 10573014
• 11709013
• 13520885
• 14299791
• 1536174
• 17236192
• 17999364
• 19449424
• 21035103
• 3112157
• 3182841
• 3220479
• 4100752
• 7642541
• 7721876
• 7859283
• 8304335
• 8530046
• 8872475
• 9129742
• 9529347
• 9792885