Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25
Filtrar
1.
Ophthalmol Retina ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38750936

RESUMO

PURPOSE: To report a previously undescribed finding of peripapillary hyperreflective ovoid mass-like structures (PHOMS) in Stickler syndrome. DESIGN: Noncomparative case series. SUBJECTS: Twenty-two eyes with anomalous optic disc from 11 Stickler syndrome patients were identified and imaged. METHODS: Peripapillary hyperreflective ovoid mass-like structures were graded using enhanced-depth imaging OCT (EDI-OCT) according to the consensus recommendations of the Optic Disc Drusen Studies Consortium. All EDI-OCT scans were obtained using the Heidelberg Spectralis (Heidelberg Engineering) with a dense horizontal raster (15 × 10°, 97 sections) centered on the optic nerve head and graded by 2 independent assessors. In case of disagreement, the image was graded by a third assessor. The presence of any coexisting optic disc drusen was also assessed using EDI-OCT and autofluorescence. MAIN OUTCOME MEASURES: The presence of PHOMS, clinical characteristics and genetic mutations. RESULTS: A pilot sample of 22 eyes with phenotypic optic disc abnormalities from 11 Stickler syndrome patients were identified and imaged. Eight patients were female and 3 were male. The mean age was 31 years (13-58 years). Peripapillary hyperreflective ovoid mass-like structures were present in 91% (n = 20) of imaged eyes. Seventy percent (n = 14) were type 1 Stickler syndrome and 30% (n = 6) were type 2 Stickler syndrome. All eyes were myopic and the degree of myopia did not seem to affect whether or not PHOMS was present in this cohort. One eye with PHOMS had retinal detachment, and 77.3% (n = 17) of eyes had undergone 360o prophylactic retinopexy. Thirty-two percent (n = 7) of eyes with PHOMS were present in patients with coexisting hearing loss and 22.7% (n = 5) had orofacial manifestation of Stickler syndrome in the form of a cleft palate. Seventy-seven percent (n = 15) of eyes with PHOMS were present in patients who reported joint laxity or symptoms of arthritis. No coexisting optic disc drusen were identified and raised intracranial pressure was also excluded after neurological investigation. CONCLUSIONS: These data suggest that PHOMS are a novel finding in Stickler syndrome patients and should be considered when evaluating the optic nerves of these patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

2.
Br J Ophthalmol ; 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38041683

RESUMO

Literature discussing fellow eye risk in patients with rhegmatogenous retinal detachment secondary to posterior vitreous detachment (PVD) is limited, particularly in subgroups where this risk may be greater than the general population. In this retrospective consecutive case series with 107 study patients, the risk of retinal tears in fellow eyes of patients with horseshoe tears in three or more quadrants of their presenting eye, secondary to PVD, was 81%. The fellow eye risk is high in this subgroup of patients, and it is important to inform them to seek prompt attention when symptoms of PVD develop in their fellow eye.

4.
Arch Dis Child ; 108(10): 789-791, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36882306

RESUMO

Legg-Calve-Perthes' disease (LCP) is defined as avascular necrosis of the femoral head in a child and may present to a variety of disciplines from general practice to orthopaedics, paediatrics, rheumatology and more. The Stickler syndromes are a group of disorders of type II, IX and XI collagen associated with hip dysplasia, retinal detachment, deafness and cleft palate. The pathogenesis of LCP disease remains an enigma but there have been a small number of cases reporting variants in the gene encoding the α1 chain of type II collagen (COL2A1). Variants in COL2A1 are known to cause type 1 Stickler syndrome (MIM 108300, 609508), which is a connective tissue disorder with a very high risk of childhood blindness, and it is also associated with dysplastic development of the femoral head. It is unclear whether COL2A1 variants make a definitive contribution to both disorders, or whether the two are indistinguishable using current clinical diagnostic techniques. In this paper, we compare the two conditions and present a case series of 19 patients with genetically confirmed type 1 Stickler syndrome presenting with a historic diagnosis of LCP. In contrast to isolated LCP, children with type 1 Stickler syndrome have a very high risk of blindness from giant retinal tear detachment, but this is now largely preventable if a timely diagnosis is made. This paper highlights the potential for avoidable blindness in children presenting to clinicians with features suggestive of LCP disease but with underlying Stickler syndrome and proposes a simple scoring system to assist clinicians.


Assuntos
Artrite , Doenças do Tecido Conjuntivo , Doença de Legg-Calve-Perthes , Humanos , Criança , Doença de Legg-Calve-Perthes/complicações , Doença de Legg-Calve-Perthes/diagnóstico , Doença de Legg-Calve-Perthes/genética , Artrite/complicações , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/diagnóstico , Doenças do Tecido Conjuntivo/genética , Cegueira/genética , Cegueira/prevenção & controle
5.
Eur Arch Otorhinolaryngol ; 278(7): 2261-2268, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32901364

RESUMO

PURPOSE: To present the extent and site of lesion of auditory dysfunction in a large cohort of individuals with type 2 Stickler Syndrome. Type 2 Stickler Syndrome results from a mutation in the gene coding for α-1 type XI pro-collagen, which has been identified in the human vitreous, cartilage and the cochlea of the mouse. The condition is characterised by classic ocular abnormalities, auditory dysfunction, osteoarthropathy and oro-facial dysplasia. METHODS: This is a population study which used a combination of audiometric, tympanometric, and self-report measures on a series of 65 individuals (mean age 29.2 years, range 3-70, female 63.1%) with genetically confirmed type 2 Stickler Syndrome. RESULTS: Hearing impairment was identified in at least one ear for 69% of individuals. Analysis against age-matched normative data showed that reduced hearing sensitivity was present across all test frequencies. Sensorineural hearing loss was most common (77% of ears), with conductive (3%), mixed (7%) and no hearing loss (13%), respectively. The proportion of hypermobile tympanic membranes (24%) was less than previously documented in type 1 Stickler Syndrome. When present, this appears to arise as a direct result of collagen abnormalities in the middle ear. Self-report measures of speech and spatial hearing in sound were comparable to a non-syndromic cohort with similar audiometric thresholds. CONCLUSIONS: Auditory impairment in type 2 Stickler Syndrome is predominantly associated with cochlear hearing loss of varying severities across affected individuals. The impact on hearing thresholds can be seen across the frequency range, suggesting a contribution of defective collagen throughout the cochlea. Self-report questionnaires showed that difficulties understanding speech, and spatial information in sound (such as that used for localisation), were worse than a young, normal-hearing population but comparable to a non-syndromic cohort with similar audiometric thresholds. Therefore, it is likely that hearing loss in type 2 Stickler Syndrome arises in the auditory periphery, without significant central processing deficits.


Assuntos
Doenças do Tecido Conjuntivo , Perda Auditiva Neurossensorial , Descolamento Retiniano , Animais , Artrite , Colágeno Tipo XI/genética , Feminino , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/genética , Camundongos , Mutação
6.
Ther Adv Rare Dis ; 1: 2633004020978661, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-37180493

RESUMO

The Stickler syndromes are the leading cause of inherited retinal detachment and the most common cause of rhegmatogenous retinal detachment in childhood. The clinical and molecular genetic spectrum of this connective tissue disorder is discussed in this article, emphasising the key role the ophthalmologist has to play in the identification, diagnosis and prevention of blindness in the increasingly widely recognised sub-groups with ocular-only (or minimal systemic) involvement. Without diagnosis and prophylaxis in such high-risk subgroups, these patients are at high risk of Giant Retinal Tear detachment and blindness, especially in the paediatric population, where late or second eye involvement is common. Initially considered a monogenic disorder, there are now known to be at least 11 distinct phenotypic subgroups in addition to allied connective tissue disorders that can present to the clinician as part of the differential diagnosis. Plain language summary: Treatment and diagnostic advances in Stickler syndrome The Stickler syndromes are a group of related connective tissue disorders that are associated with short-sight and a very high risk of blindness from detachment of the retina - the light sensitive film at the back of the eye. Other features include cleft palate, deafness and premature arthritis. It is the most common cause of retinal detachment in children and the most common cause of familial or inherited retinal detachment. In contrast to most other forms of blinding genetic eye disease, blindness from retinal detachment in Stickler syndrome is largely avoidable with accurate diagnosis and prophylactic (preventive) surgery. Recent advances in the understanding of the genetic causes of Stickler syndrome mean that the diagnosis can now be confirmed in over 95% of cases and, most importantly, the patient's individual risk of retinal detachment can be graded. Preventative surgery is hugely effective in reducing the incidence of retinal detachment in those patients shown to be at high risk. NHS England have led the way in the multidisciplinary care for patients with Stickler syndrome by launching a highly specialist service that has been free at point of care to all NHS patients in England since 2011 (https://www.england.nhs.uk/commissioning/spec-services/highly-spec-services, www.vitreoretinalservice.org).

11.
Ophthalmology ; 125(2): 227-236, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28867131

RESUMO

PURPOSE: Despite posterior vitreous detachment being a common ocular event affecting most individuals in an aging population, there is little consensus regarding its precise anatomic definition. We investigated the morphologic appearance and molecular composition of the posterior hyaloid membrane to determine whether the structure clinically observed enveloping the posterior vitreous surface after posterior vitreous detachment is a true basement membrane and to postulate its origin. Understanding the relationship between the vitreous (in both its attached and detached state) and the internal limiting membrane of the retina is essential to understanding the cause of rhegmatogenous retinal detachment and vitreoretinal interface disorders, as well as potential future prophylactic and treatment strategies. DESIGN: Clinicohistologic correlation study. PARTICIPANTS: Thirty-six human donor globes. METHODS: Vitreous bodies identified to have posterior vitreous detachment were examined with phase-contrast microscopy and confocal microscopy after immunohistochemically staining for collagen IV basement membrane markers, in addition to extracellular proteins that characterize the vitreoretinal junction (fibronectin, laminin) and vitreous gel (opticin) markers. The posterior retina similarly was stained to evaluate the internal limiting membrane. Findings were correlated to the clinical appearance of the posterior hyaloid membrane observed during slit-lamp biomicroscopy after posterior vitreous detachment and compared with previously published studies. MAIN OUTCOME MEASURES: Morphologic appearance and molecular composition of the posterior hyaloid membrane. RESULTS: Phase-contrast microscopy consistently identified a creased and distinct glassy membranous sheet enveloping the posterior vitreous surface, correlating closely with the posterior hyaloid membrane observed during slit-lamp biomicroscopy in patients with posterior vitreous detachment. Immunofluorescent confocal micrographs demonstrated the enveloping membranous structure identified on phase-contrast microscopy to show positive stain results for type IV collagen. Immunofluorescence of the residual intact internal limiting membrane on the retinal surface also showed positive stain results for type IV collagen. CONCLUSIONS: The results of this study provide immunohistochemical evidence that the posterior hyaloid membrane is a true basement membrane enveloping the posterior hyaloid surface. Because this membranous structure is observed only after posterior vitreous detachment, the results of this study indicate that it forms part of the internal limiting membrane when the vitreous is in its attached state.


Assuntos
Membrana Basal/diagnóstico por imagem , Colágeno/metabolismo , Corpo Vítreo/patologia , Descolamento do Vítreo/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Membrana Basal/química , Feminino , Humanos , Imageamento Tridimensional , Imuno-Histoquímica , Masculino , Microscopia Acústica , Microscopia Confocal , Pessoa de Meia-Idade , Estudos Prospectivos , Vitrectomia , Corpo Vítreo/cirurgia , Descolamento do Vítreo/cirurgia
13.
Hum Mutat ; 37(10): 1085-96, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27406592

RESUMO

COL2A1 mutations causing haploinsufficiency of type II collagen cause type 1 Stickler syndrome that has a high risk of retinal detachment and failure of the vitreous to develop normally. Exon 2 of COL2A1 is alternatively spliced, expressed in the eye but not in mature cartilage and encodes a region that binds growth factors TGFß1 and BMP-2. We investigated how both an apparently de novo variant and a polymorphism in intron 2 altered the efficiency of COL2A1 exon 2 splicing and how the latter may act as a predisposing risk factor for the occurrence of posterior vitreous detachment (PVD)-associated rhegmatogenous retinal detachment (RRD) in the general population. Using amplification of illegitimate transcripts and allele-specific minigenes expressed in cultured cells, we demonstrate variability in exon 2 inclusion not only between different control individuals, but also between different COL2A1 alleles. We identify transacting factors that bind to allele-specific RNA sequences, and investigate the effect of knockdown and overexpression of these factors on exon 2 splicing efficiency. Finally, using a specific cohort of patients with PVD-associated RRD and a control population, we demonstrate a significant difference in the frequency of the COL2A1 intronic variant rs1635532 between the two groups.


Assuntos
Processamento Alternativo , Colágeno Tipo II/genética , Oftalmopatias Hereditárias/genética , Mutação , Descolamento Retiniano/genética , Células Cultivadas , Éxons , Predisposição Genética para Doença , Humanos , Íntrons , Análise de Sequência de DNA
14.
JAMA Ophthalmol ; 134(7): 827-30, 2016 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-27227434

RESUMO

IMPORTANCE: In-the-bag intraocular lens dislocation is an uncommon but serious complication of cataract surgery in patients with previous repair of retinal detachment. The causative mechanism is currently unknown. We report histologic findings from a retrospective case series from 1993 to 2010 and suggest a possible mechanism to explain this association. OBSERVATIONS: Clinical characteristics of 8 patients presenting with in-the-bag intraocular lens dislocation after repair of retinal detachment were evaluated. Explanted capsular bags from 3 of these patients were compared with pathologic changes of crystalline lenses associated with retinal detachment. Histologic examination of the explanted capsular bags revealed a paucicellular membrane that covered the concertina-like folded surface of the lens capsule. The lens capsule was devoid of epithelial cell nuclei and showed excessive thickening with the presence of spindle-shaped cells, such as fibroblasts. Collagen fibers were noted in the extracellular matrix. CONCLUSIONS AND RELEVANCE: Previous studies of crystalline lens pathologic findings associated with retinal detachment have shown changes in the epithelium with migration and subsequent metaplasia of epithelial cells, resulting in excessive thickening of the anterior capsule with a layer of fibrous tissue. In this retrospective series, similar histologic findings were seen, suggesting that zonular dehiscence and lens dislocation may result from progressive capsular contraction secondary to retinal detachment-induced lens epithelial metaplasia.


Assuntos
Migração do Implante de Lente Intraocular/etiologia , Células Epiteliais/patologia , Cápsula do Cristalino/patologia , Complicações Pós-Operatórias , Descolamento Retiniano/cirurgia , Idoso , Migração do Implante de Lente Intraocular/diagnóstico , Humanos , Masculino , Metaplasia/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Lâmpada de Fenda
15.
Ophthalmology ; 121(8): 1588-97, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24793526

RESUMO

PURPOSE: The Stickler syndromes are the most common causes of inherited and childhood retinal detachment; however, no consensus exists regarding the effectiveness of prophylactic intervention. We evaluate the long-term safety and efficacy of the Cambridge prophylactic cryotherapy protocol, a standardized retinal prophylactic treatment developed to prevent retinal detachment arising from giant retinal tears in type 1 Stickler syndrome. DESIGN: Retrospective comparative case series. PARTICIPANTS: Four hundred eighty seven patients with type 1 Stickler syndrome. METHODS: Time to retinal detachment was compared between patients who received bilateral prophylaxis and untreated controls, with and without individual patient matching. Patients receiving unilateral prophylaxis (after fellow eye retinal detachment) were similarly compared with an appropriate control subgroup. Individual patient matching ensured equal age and follow-up between groups and that an appropriate control (who had not suffered a retinal detachment before the age at which their individually matched treatment patient underwent prophylactic treatment) was selected. Matching was blinded to outcome events. Individual patient matching protocols purposely weighted bias against the effectiveness of treatment. All treatment side effects are reported. MAIN OUTCOME MEASURES: Time to retinal detachment and side effects occurring after prophylactic treatment. RESULTS: The bilateral control group (n = 194) had a 7.4-fold increased risk of retinal detachment compared to the bilateral prophylaxis group (n = 229) (hazard ratio [HR], 7.40; 95% confidence interval [CI], 4.53-12.08; P<0.001); the matched bilateral control group (n = 165) had a 5.0-fold increased risk compared to the matched bilateral prophylaxis group (n = 165) (HR, 4.97; 95% CI, 2.82-8.78; P<0.001). The unilateral control group (n = 104) had a 10.3-fold increased risk of retinal detachment compared to the unilateral prophylaxis group (n = 64) (HR, 10.29; 95% CI, 4.96-21.36; P<0.001); the matched unilateral control group (n = 39) had a 8.4-fold increased risk compared to the matched unilateral prophylaxis group (n = 39) (HR, 8.36; 95% CI, 3.24-21.57; P<0.001). No significant long-term side effects occurred. CONCLUSIONS: In the largest global cohort of type 1 Stickler syndrome patients published, all analyses indicate that the Cambridge prophylactic cryotherapy protocol is safe and markedly reduces the risk of retinal detachment.


Assuntos
Artrite/complicações , Doenças do Tecido Conjuntivo/complicações , Crioterapia , Perda Auditiva Neurossensorial/complicações , Descolamento Retiniano/prevenção & controle , Adolescente , Adulto , Artrite/diagnóstico , Artrite/genética , Protocolos Clínicos , Colágeno Tipo II/genética , Doenças do Tecido Conjuntivo/diagnóstico , Doenças do Tecido Conjuntivo/genética , Análise Mutacional de DNA , Feminino , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/genética , Humanos , Masculino , Linhagem , Descolamento Retiniano/complicações , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Descolamento Retiniano/genética , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Adulto Jovem
16.
J Med Genet ; 50(11): 765-71, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23922384

RESUMO

BACKGROUND: Stickler syndromes types 1, 2 and 3 are usually dominant disorders caused by mutations in the genes COL2A1, COL11A1 and COL11A2 that encode the fibrillar collagens types II and XI present in cartilage and vitreous. Rare recessive forms of Stickler syndrome exist that are due to mutations in genes encoding type IX collagen (COL9A1 type 4 Stickler syndrome and COL9A2 type 5 Stickler syndrome). Recently, recessive mutations in the COL11A1 gene have been demonstrated to result in fibrochondrogenesis, a much more severe skeletal dysplasia, which is often lethal. Here we demonstrate that some mutations in COL11A1 are recessive, modified by alternative splicing and result in type 2 Stickler syndrome rather than fibrochondrogenesis. METHODS: Patients referred to the national Stickler syndrome diagnostic service for England, UK were assessed clinically and subsequently sequenced for mutations in COL11A1. Additional in silico and functional studies to assess the effect of sequence variants on pre-mRNA processing and collagen structure were performed. RESULTS: In three different families, heterozygous COL11A1 biallelic null, null/missense or silent/missense mutations, were found. They resulted in a recessive form of type 2 Stickler syndrome characterised by particularly profound hearing loss and are clinically distinct from the recessive types 4 and 5 variants of Stickler syndrome. One mutant allele in each family is capable of synthesising a normal α1(XI) procollagen molecule, via variable pre-mRNA processing. CONCLUSION: This new variant has important implications for molecular diagnosis and counselling families with type 2 Stickler syndrome.


Assuntos
Processamento Alternativo , Colágeno Tipo XI/genética , Doenças do Tecido Conjuntivo/genética , Perda Auditiva/genética , Mutação , Descolamento do Vítreo/genética , Adulto , Sequência de Aminoácidos , Pré-Escolar , Colágeno Tipo XI/deficiência , Feminino , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Linhagem
17.
Eur J Hum Genet ; 20(5): 552-8, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22189268

RESUMO

UK NHS diagnostic service sequence analysis of genes generally examines and reports on variations within a designated region 5' and 3' of each exon, typically 30 bp up and downstream. However, because of the degenerate nature of the splice sites, intronic variants outside the AG and GT dinucleotides of the acceptor and donor splice sites (ASS and DSS) are most often classified as being of unknown clinical significance, unless there is some functional evidence of their pathogenicity. It is now becoming clear that mutations deep within introns can also interfere with normal processing of pre-mRNA and result in pathogenic effects on the mature transcript. In diagnostic laboratories, these deep intronic variants most often fall outside of the regions analysed and so are rarely reported. With the likelihood that next generation sequencing will identify more of these unclassified variants, it will become important to perform additional studies to determine the pathogenicity of such sequence anomalies. Here, we analyse variants detected in either COL2A1 or COL11A1 in patients with Stickler syndrome. These have been analysed both in silico and functionally using either RNA isolated from the patient's cells or, more commonly, minigenes as splicing reporters. We show that deep intronic mutations are not a rare occurrence, including one variant that results in multiple transcripts, where both de novo donor and ASS are created by the mutation. Another variant produces transcripts that result in either haploinsufficiency or a dominant negative effect, potentially modifying the disease phenotype.


Assuntos
Colágeno Tipo II/genética , Colágeno Tipo XI/genética , Íntrons , Mutação , Splicing de RNA , Processamento Alternativo , Sequência de Bases , Colágeno Tipo XI/metabolismo , Éxons , Humanos , Dados de Sequência Molecular , Sítios de Splice de RNA , Análise de Sequência de DNA
18.
Hum Mutat ; 31(6): E1461-71, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20513134

RESUMO

Stickler syndrome is a dominantly inherited disorder affecting the fibrillar type II/XI collagen molecules expressed in vitreous and cartilage. Mutations have been found in COL2A1, COL11A1 and COL11A2. It has a highly variable phenotype that can include midline clefting, hearing loss, premature osteoarthritis, congenital high myopia and blindness through retinal detachment. Although the systemic phenotype is highly variable, the vitreous phenotype has been used successfully to differentiate between patients with mutations in these different genes. Mutations in COL2A1 usually result in a congenital membranous vitreous anomaly. In contrast mutations in COL11A1 result in a different vitreous phenotype where the lamellae have an irregular and beaded appearance. However, it is now apparent that a new sub-group of COL2A1 mutations is emerging that result in a different phenotype with a hypoplastic vitreous that fills the posterior chamber of the eye, and is either optically empty or has sparse irregular lamellae. Here we characterise a further 89 families with Stickler syndrome or a type II collagenopathy, and correlate the mutations with the vitreous phenotype. We have identified 57 novel mutations including missense changes in both COL2A1 and COL11A1 and have also detected two cases of complete COL2A1 gene deletions using MLPA.


Assuntos
Colágeno Tipo II/genética , Colágeno Tipo XI/genética , Oftalmopatias Hereditárias/genética , Mutação , Corpo Vítreo/anormalidades , Sequência de Bases , Análise Mutacional de DNA , Oftalmopatias Hereditárias/patologia , Saúde da Família , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Síndrome
19.
Ophthalmology ; 115(1): 164-8, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17675240

RESUMO

PURPOSE: To report the prevalence of retinal detachment (RD) and results of prophylaxis against detachment from a giant retinal tear in a large cohort of patients with type 1 Stickler syndrome. DESIGN: Retrospective study. PARTICIPANTS: Two hundred four type 1 Stickler syndrome patients. METHOD: Pedigrees and individuals with type 1 Stickler syndrome were identified from the vitreous research clinic and divided into 3 groups. Group 1 consisted of patients who received no prophylaxis (control group). Group 2 consisted of patients who had bilateral 360 degrees prophylactic cryotherapy (study group). Group 3 consisted of patients referred with unilateral RD for surgical repair and who underwent prophylaxis in the fellow eye (mixed group). MAIN OUTCOME MEASURES: Retinal status after prophylaxis, with failure of prophylaxis being defined as the development of RD or retinal tears needing further retinopexy. RESULTS: Of 111 patients who had no prophylactic retinopexy (group 1; mean age, 49 years), 73% (81/111) suffered RD and 48% (53/111) were bilateral. Of 62 patients who had bilateral prophylactic cryotherapy (group 2; mean age, 21 years), 8% (5/62) suffered failure of prophylaxis. There were no cases of bilateral detachments. The mean follow-up period was 11.5 years. In 31 patients who had unilateral prophylactic cryotherapy to the fellow eye (group 3; mean age, 36 years), failure occurred in 10% (3/31) of cases with a mean follow-up of 15.5 years. The prevalence of failure of prophylaxis in treated patients was significantly less than prevalence of RD in untreated patients (chi2(1) = 119.2, P<0.001). CONCLUSION: Prophylactic cryotherapy substantially reduces the risk of RD in type 1 Stickler syndrome and, in this series, eliminated the risk of bilateral detachments.


Assuntos
Criocirurgia , Oftalmopatias/complicações , Degeneração Retiniana/complicações , Descolamento Retiniano/prevenção & controle , Corpo Vítreo/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Colágeno Tipo II/genética , Análise Mutacional de DNA , Oftalmopatias/diagnóstico , Oftalmopatias/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Degeneração Retiniana/diagnóstico , Degeneração Retiniana/genética , Descolamento Retiniano/epidemiologia , Descolamento Retiniano/etiologia , Perfurações Retinianas/epidemiologia , Perfurações Retinianas/etiologia , Perfurações Retinianas/prevenção & controle , Estudos Retrospectivos , Síndrome
20.
Hum Mutat ; 28(6): 639, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17437277

RESUMO

Stickler syndrome due to mutations in COL2A1 is usually the result of premature termination codons and nonsense mediated decay resulting in haploinsufficiency of type II collagen. Here we present two missense mutations and one apparently silent mutation that each result in Stickler syndrome, but via different molecular mechanisms. One alters the translation initiating ATG codon. The second mutation is a unique glycine substitution in the minor collagen helix of the procollagen. To our knowledge a glycine substitution has not previously been reported in this region of fibrillar procollagens. The third mutation appears to be a silent change altering a GGC codon to GGT both for glycine, but use of a splicing reporter assay demonstrates that it results in missplicing and a shift in the reading frame.


Assuntos
Processamento Alternativo/genética , Colágeno Tipo II/genética , Mutação de Sentido Incorreto , Osteoartrite/genética , Descolamento Retiniano/genética , Corpo Vítreo/anormalidades , Adulto , Substituição de Aminoácidos/genética , Células Cultivadas , Análise Mutacional de DNA , Éxons , Feminino , Fibroblastos/metabolismo , Genes Dominantes , Heterozigoto , Homozigoto , Humanos , Masculino , Mosaicismo , Palato/anormalidades , Linhagem , Polimorfismo Genético , Síndrome
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...