Myocilin mutations in a population-based sample of cases with open-angle glaucoma: the Rotterdam Study

Hulsman, Caroline A. A.; Jong, Paulus T. V. M. de; Lettink, Marjolein; Duijn, Cornelia M. van; Hofman, Albert; Bergen, Arthur A. B.

doi:10.1007/s00417-002-0455-1

Cited by 23 publications

(25 citation statements)

References 35 publications

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“…The frequency of this single mutation, 5%, is the highest ever observed. It compares only to that reported in patients from Western Switzerland (Mataftsi et al, 2001), and it is at least twice that reported in most other studies, including in patients from other Western European countries (Cobb et al, 2002;Hulsman et al, 2002a;Michel-Rautenstrauss et al, 2002). Of note, this mutation was not detected in African and in Asian POAG patients (Yoon et al, 1999;Kubota et al, 2000;Challa et al, 2002;Mukhopadhyay et al, 2002;Pang et al, 2002;Melki et al, 2003).…”

Section: Allelic Associations With Myoc Mutations Denote Founding Effsupporting

confidence: 61%

“…Therefore, this patient represented a new branch of this very large POAG pedigree. The other patient presented several discordant alleles, notably at NGA13 and D1S1165, and had therefore inherited the N480K mutation from a different ancestor (Hulsman et al, 2002a). Similarly, the patient with the I499F mutation possessed alleles that were previously associated with this mutation in two large families from Western France .…”

Section: Allelic Associations With Myoc Mutations Denote Founding Effmentioning

confidence: 95%

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Myocilin analysis by DHPLC in French POAG patients: Increased prevalence of Q368X mutation

et al. 2003

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Primary open-angle glaucoma (POAG) is a prevalent optic neuropathy with complex genetics. A small number of patients carry a mutation in the coding region of the myocilin (MYOC) gene. The nature and the frequency of these mutations, however, vary substantially, notably with the age at onset and the ethnic origin of the patients. Here, we showed that denaturing high performance liquid chromatography (DHPLC) is an appropriate method for screening carriers of MYOC mutations. We have applied the method to a group of 237 POAG patients and 108 control subjects from France. Mutations were found in 17 (7.5%) patients and in none of the controls. A single mutation, Q368X (c.1102C>T), accounted for the majority (12/17) of these mutations, corresponding to a frequency of 5% among POAG patients, the highest ever reported for this mutation. Furthermore, analysis of allelic associations at closely linked microsatellite markers indicated that most, if not all, patients inherited Q368X from a same ancestor. Five other patients carried four distinct mutations, including N480K (c.1440C>A) (2 cases), I499F (c.1495A>T), G367R (c.1099G>A) and T438I (c.1313C>T), which is reported here for the first time. Altogether, MYOC mutations in French patients were associated with a significantly increased intraocular pressure at diagnosis. In addition, the age at diagnosis of patients with a mutation other than Q368X was significantly younger than that of Q368X carriers or of patients with a normal MYOC. Based on these observations, a screening strategy of MYOC mutations in French POAG patients is briefly outlined.

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Section: Allelic Associations With Myoc Mutations Denote Founding Effsupporting

confidence: 61%

Section: Allelic Associations With Myoc Mutations Denote Founding Effmentioning

confidence: 95%

Myocilin analysis by DHPLC in French POAG patients: Increased prevalence of Q368X mutation

et al. 2003

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“…14 Interestingly, haplotype analysis with 26 flanking markers spanning 8 cM showed that Asn480Lys mutations for most Northern French and Dutch had at least 2 different origins since flanking alleles diverged, demonstrating that it was a recurrent mutation. 13,14 The initial report of mutations in MYOC in POAG cases by Stone et al 7 was followed by a series of studies reporting new causative mutations and polymorphic single nucleotide polymorphisms in individuals and families of European, African, and Asian ancestry. 10,15,16 In some cases, there are distinct ethno-geographic distributions in the prevalence for some glaucoma causative variants.…”

mentioning

confidence: 99%

Recurrent Myocilin Asn480Lys Glaucoma Causative Mutation Arises De Novo in a Family of Andean Descent

Guevara‐Fujita

Perez-Grossmann

Estrada-Cuzcano

et al. 2008

Journal of Glaucoma

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In the study of MYOC variants in 11 POAG Peruvian families, we have found a family of ethnically admixed origin with polymorphism Arg76Lys and a family of Andean descent bearing a third event of the Asn480Lys, the MYOC mutation that has been reported in the highest number of POAG patients (>80 cases). Analysis of this family could contribute with information about disease manifestation, progression, and treatment response in the context of a distinct genetic background and also climatic, altitude, and socioeconomical conditions.

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“…Notably, however, no other mutations were identified, despite sequencing the olfactomedin domain of exon 3 where 85-90% of mutations cluster (Fingert et al 1999). Other studies have consistently identified mutations in 2.5-4.5% of all glaucoma probands across several different populations (Faucher et al 2002;Fingert et al 1999;Hulsman et al 2002;Mataftsi et al 2001;Stone et al 1997). This suggests that the overall frequency of MYOC mutations in unselected UK POAG patients is lower than that previously reported in several other countries.…”

Section: Discussionmentioning

confidence: 65%

“…These mutations were then found in 4.4% of 227 American POAG patients with an affected first-degree relative and 2.9% of 103 patients that were unselected for family history. Additional mutations have since been identified in other glaucoma families of diverse origin, while population-based studies have confirmed that MYOC mutations are involved in a significant proportion of all POAG cases and are not confined to those with a strong family history or juvenile onset (Adam et al 1997;Alward et al 1998;Cobb et al 2002;Faucher et al 2002;Fingert et al 1999;Hulsman et al 2002;Mataftsi et al 2001;Suzuki et al 1997). The majority of mutations are clustered in a single exon that encodes an evolutionarily conserved domain with homology to the frog olfactomedin protein (Fingert et al 1999).…”

Section: Introductionmentioning

confidence: 92%

Low prevalence of MYOC mutations in UK primary open-angle glaucoma patients limits the utility of genetic testing

et al. 2004

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Primary open angle glaucoma (POAG) affects 1% of people over age 40. Early detection and treatment can prevent blindness, but the disease is often asymptomatic until a late stage. Positive family history is an important risk factor and previous studies indicate that approximately 5% of POAG results from mutations in the myocilin ( MYOC) gene, raising the possibility of identifying individuals genetically predisposed to glaucoma. We collected DNA samples from 426 unselected UK POAG patients and analyzed them for MYOC mutations. The Q368X mutation was found in six patients (1.4%). No other mutations were identified, suggesting that amongst patients unselected for family history, the prevalence of MYOC mutations in the UK is lower than in other populations. Genetic and glaucoma screening was offered to first-degree relatives of these six probands (group 1) and of age/sex-matched mutation-negative controls (group 2). Of 11 group-1 relatives, three carried Q368X, one of whom already had glaucoma. Notably, of the 13 relatives in both groups who were mutation negative, one was already being treated for ocular hypertension. We therefore caution against changing glaucoma surveillance regimens in such individuals and suggest that routine untargeted genetic testing for MYOC mutations in patients with POAG would be of limited value until additional significant genetic risk factors are identified.

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Myocilin mutations in a population-based sample of cases with open-angle glaucoma: the Rotterdam Study

Cited by 23 publications

References 35 publications

Myocilin analysis by DHPLC in French POAG patients: Increased prevalence of Q368X mutation

Myocilin analysis by DHPLC in French POAG patients: Increased prevalence of Q368X mutation

Recurrent Myocilin Asn480Lys Glaucoma Causative Mutation Arises De Novo in a Family of Andean Descent

Low prevalence of MYOC mutations in UK primary open-angle glaucoma patients limits the utility of genetic testing

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