Dominant Stickler Syndrome

Soh, Zack; Richards, Allan J.; McNinch, Annie; Alexander, Philip; Martin, Howard; Snead, Martin P.

doi:10.3390/genes13061089

Cited by 19 publications

(30 citation statements)

References 47 publications

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“…Over the past 20 years, a taxonomy of the SS subgroups based on vitreous characteristics has emerged. It has been shown that this taxonomy is a reliable strategy for both diagnosing SS and directing molecular study [11,12] . Type 3 SS is a non-ocular type of SS, manifesting as prelingual development of sensorineural hearing loss, growth of the epiphyses with generalized shortening of the limbs, and vertebral body dysplasia.…”

Section: Discussionmentioning

confidence: 99%

“…The haploinsu ciency of COL2A1, the encoding gene for collagen type II alpha 1 chain, is responsible for autosomal dominant type 1 SS [10] . Type 2 SS (OMIM #604841), representing the remaining 10-20% of cases, is usually caused by monoallelic mutations in COL11A1 which encodes the collagen type XI alpha 1 chain [11] . However, biallelic pathogenic variants of COL11A1 have also been reported occasionally [12] .…”

Section: Introductionmentioning

confidence: 99%

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Autosomal recessive type 3 Stickler syndrome caused by compound heterozygous mutations in COL11A2: a case report

Ran

Liu

et al. 2022

Preprint

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Background Stickler syndrome (SS) is a group of hereditary collagenopathies caused by a variety of collagen and non-collagen genes. Affected patients have characteristic manifestations involving ophthalmic, articular, craniofacial and auditory disorders. SS is classified into several subtypes according to clinical and molecular features. Type 3 SS is ultra-rare, known as non-ocular SS or otospondylomegaepiphyseal dysplasia (OSMED) with only a few ballistic COL11A2 variants reported to date. Case presentation A 29-year-old Chinese male was referred to our hospital for hearing loss and multiple joint pain. He presented a phenotype highly suggestive of OSMED, including progressive sensorineural deafness, spondyloepiphyseal dysplasia with large epiphyses, platyspondyly, degenerative osteoarthritis, and sunken nasal bridge. We detected compound heterozygous mutations in COL11A2, both of which are predicted to be splicing mutations. One of the mutations is synonymous mutation c.3774C > T (p.Gly1258Gly) whereas it may cause splicing mutation predicted by in silico analysis, the other is a novel intron mutation c.4750 + 5 G > A which is a highly conservative site across several species. The patient received medications to alleviate the joint pain and osteoporosis. We also present a review of the current known pathogenic mutation spectrum of COL11A2 in patients with type 3 SS. Conclusion For patients with characteristic manifestations of SS syndrome, next-generation genetic analysis is beneficial for precision medical care and genetic counseling.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Autosomal recessive type 3 Stickler syndrome caused by compound heterozygous mutations in COL11A2: a case report

Ran

Liu

et al. 2022

Preprint

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“…Stickler Syndrome as one of many syndromes associated with COL2A1 mutations, presents with a broad range of anatomical findings and ophthalmological complications, often leading to difficulty with diagnosis, treatment, and genetic counseling [ 4 ]. Recent reviews have begun to detail these varied presentations with genotype-phenotype correlations as technology continues to progress [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Autosomal dominant and recessive inheritance patterns associated with different target genes (COL2A1, COL11A1, COL11A2, COL9A1, and COL9A3) have been identified [ 1 , 3 , 5 , 6 , 7 ]. Most patients with autosomal dominant Stickler Syndrome carry one mutated collagen allele, however, there has been one reported case of biallelic heterozygosity of COL11A1 mutations which resulted in retinal atrophy and severe hearing loss [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…Following trimerization and cleavage of the pro-peptides, mature type II collagen forms a necessary fibrillar network within the extracellular matrix of cartilage, the vitreous, and intervertebral discs [ 9 , 10 , 11 , 12 , 13 ]. While there are many diseases that are associated with mutations in COL2A1, Stickler syndrome, an arthro-ophthalmopathy, is most common [ 3 , 4 , 5 , 12 , 13 ]. Predominantly characterized by the ocular findings, namely vitreoretinal degeneration and pathologic myopia often complicated by retinal tears and detachments, systemic findings vary but include micrognathia, cleft palate, early osteoarthritis and joint problems, and deafness [ 2 , 3 , 4 , 5 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Characteristics of a Three-Generation Family with Stickler Syndrome Type I Carrying Two Different COL2A1 Mutations

Jacobson

Besirli

Bohnsack

2023

Genes

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Stickler Syndrome is typically characterized by ophthalmic manifestations including vitreous degeneration and axial lengthening that predispose to retinal detachment. Systemic findings consist of micrognathia, cleft palate, sensorineural hearing loss, and joint abnormalities. COL2A1 mutations are the most common, however, there is a lack of genotype-phenotype correlations. Retrospective, single-center case series of a three-generation family. Clinical features, surgical requirements, systemic manifestations, and genetic evaluations were collected. Eight individuals clinically displayed Stickler Syndrome, seven of whom had genetic confirmation, and two different COL2A1 mutations (c.3641delC and c.3853G>T) were identified. Both mutations affect exon 51, but display distinct phenotypes. The c.3641delC frameshift mutation resulted in high myopia and associated vitreous and retinal findings. Individuals with the c.3853G>T missense mutation exhibited joint abnormalities, but mild ocular manifestations. One individual in the third generation was biallelic heterozygous for both COL2A1 mutations and showed ocular and joint findings in addition to autism and severe developmental delay. These COL2A1 mutations exhibited distinct eye vs. joint manifestations. The molecular basis for these phenotypic differences remains unknown and demonstrates the need for deep phenotyping in patients with Stickler syndrome to correlate COL2A1 gene function and expression with ocular and systemic findings.

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Ophthalmic manifestations of Czech dysplasia

Soh,

Martin,

Richards

et al. 2023

American J of Med Genetics Pt A

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Czech dysplasia is an autosomal dominant type 2 collagenopathy that is caused by heterozygosity for the recurrent p.(Arg275Cys) COL2A1 variant. Affected individuals usually present with skeletal abnormalities such as metatarsal hypoplasia of the third and fourth toes and early‐onset arthropathy, as well as hearing loss. To date, no ophthalmic findings have been reported in patients with Czech dysplasia even though COL2A1 has been implicated in other ocular conditions such as type 1 Stickler syndrome. For the first time, we report the ocular findings in four families with Czech dysplasia, including type 1 vitreous anomaly, hypoplastic vitreous, retinal tears, and significant refractive error. These novel ocular findings expand the phenotype associated with Czech dysplasia and may aid clinicians as an additional diagnostic feature. Patients with congenital abnormalities of vitreous gel architecture have an increased risk of retinal detachment, and as such, patients may benefit from prophylaxis. Considering that many of the patients did not report any ocular symptoms, vitreous phenotyping is of key importance in identifying the need for counseling with regard to prophylaxis.

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Dominant Stickler Syndrome

Cited by 19 publications

References 47 publications

Autosomal recessive type 3 Stickler syndrome caused by compound heterozygous mutations in COL11A2: a case report

Autosomal recessive type 3 Stickler syndrome caused by compound heterozygous mutations in COL11A2: a case report

Characteristics of a Three-Generation Family with Stickler Syndrome Type I Carrying Two Different COL2A1 Mutations

Ophthalmic manifestations of Czech dysplasia

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