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Identification a novel MYOC gene mutation in a Chinese family with juvenile-onset open angle glaucoma.

Zhao X, Yang C, Tong Y, Zhang X, Xu L, Li Y - Mol. Vis. (2010)

Bottom Line: Bioinformatics analysis by the Garnier-Osguthorpe-Robson (GOR) method predicted the effects of variants detected on secondary structures of the MYOC protein.This missense mutation co-segregated with the disease phenotype of the family, but was not found in 100 normal controls.The finding provides pre-symptomatic molecular diagnosis for the members of this family and is useful for further genetic consultation.

View Article: PubMed Central - PubMed

Affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, China.

ABSTRACT

Purpose: To describe the clinical and genetic findings in one Chinese family with juvenile-onset open angle glaucoma (JOAG).

Methods: One family was examined clinically and a follow-up took place 5 years later. After informed consent was obtained, genomic DNA was extracted from the venous blood of all participants. Linkage analysis was performed with three microsatellite markers around the MYOC gene (D1S196, D1S2815, and D1S218) in the family. Mutation screening of all coding exons of MYOC was performed by direct sequencing of PCR-amplified DNA fragments and restriction fragment length polymorphism (RFLP) analysis. Bioinformatics analysis by the Garnier-Osguthorpe-Robson (GOR) method predicted the effects of variants detected on secondary structures of the MYOC protein.

Results: Clinical examination and pedigree analysis revealed a three- generation family with seven members diagnosed with JOAG, three with ocular hypertension, and five normal individuals. Through genotyping, the pedigree showed a linkage to the MYOC on chromosome 1q24-25. Mutation screening of MYOC in this family revealed an A-->T transition at position 1348 (p. N450Y) of the cDNA sequence. This missense mutation co-segregated with the disease phenotype of the family, but was not found in 100 normal controls. Secondary structure prediction of the p.N450Y by the GOR method revealed the replacement of a coil with a beta sheet at the amino acid 447.

Conclusions: Early onset JOAG, with incomplete penetrance, is consistent with a novel mutation in MYOC. The finding provides pre-symptomatic molecular diagnosis for the members of this family and is useful for further genetic consultation.

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Sequence alignment portion of the olfactomedin-like domain spanning the novel missense mutation p.N450Y of human MYOC and a comparison with other species.
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f5: Sequence alignment portion of the olfactomedin-like domain spanning the novel missense mutation p.N450Y of human MYOC and a comparison with other species.

Mentions: The Asn450 residue, located in the olfactomedin-like domain, is highly conserved in humans, rats, mice, cattle, dogs, and zabrafish (Figure 5). The results of GOR suggested that p.N450Y lead to a secondary structure change by replacing a coil structure with a β sheet around the Asn450 residue, which might interfere with the correct folding of the protein. In a large case control study, another mutation (p. N450D) was also detected at the Asn450 residue in a sporadic Germany patient [18]. This may imply that the Asn450 residue is very important for the activity of the olfactomedin-like domain.


Identification a novel MYOC gene mutation in a Chinese family with juvenile-onset open angle glaucoma.

Zhao X, Yang C, Tong Y, Zhang X, Xu L, Li Y - Mol. Vis. (2010)

Sequence alignment portion of the olfactomedin-like domain spanning the novel missense mutation p.N450Y of human MYOC and a comparison with other species.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2927375&req=5

f5: Sequence alignment portion of the olfactomedin-like domain spanning the novel missense mutation p.N450Y of human MYOC and a comparison with other species.
Mentions: The Asn450 residue, located in the olfactomedin-like domain, is highly conserved in humans, rats, mice, cattle, dogs, and zabrafish (Figure 5). The results of GOR suggested that p.N450Y lead to a secondary structure change by replacing a coil structure with a β sheet around the Asn450 residue, which might interfere with the correct folding of the protein. In a large case control study, another mutation (p. N450D) was also detected at the Asn450 residue in a sporadic Germany patient [18]. This may imply that the Asn450 residue is very important for the activity of the olfactomedin-like domain.

Bottom Line: Bioinformatics analysis by the Garnier-Osguthorpe-Robson (GOR) method predicted the effects of variants detected on secondary structures of the MYOC protein.This missense mutation co-segregated with the disease phenotype of the family, but was not found in 100 normal controls.The finding provides pre-symptomatic molecular diagnosis for the members of this family and is useful for further genetic consultation.

View Article: PubMed Central - PubMed

Affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, China.

ABSTRACT

Purpose: To describe the clinical and genetic findings in one Chinese family with juvenile-onset open angle glaucoma (JOAG).

Methods: One family was examined clinically and a follow-up took place 5 years later. After informed consent was obtained, genomic DNA was extracted from the venous blood of all participants. Linkage analysis was performed with three microsatellite markers around the MYOC gene (D1S196, D1S2815, and D1S218) in the family. Mutation screening of all coding exons of MYOC was performed by direct sequencing of PCR-amplified DNA fragments and restriction fragment length polymorphism (RFLP) analysis. Bioinformatics analysis by the Garnier-Osguthorpe-Robson (GOR) method predicted the effects of variants detected on secondary structures of the MYOC protein.

Results: Clinical examination and pedigree analysis revealed a three- generation family with seven members diagnosed with JOAG, three with ocular hypertension, and five normal individuals. Through genotyping, the pedigree showed a linkage to the MYOC on chromosome 1q24-25. Mutation screening of MYOC in this family revealed an A-->T transition at position 1348 (p. N450Y) of the cDNA sequence. This missense mutation co-segregated with the disease phenotype of the family, but was not found in 100 normal controls. Secondary structure prediction of the p.N450Y by the GOR method revealed the replacement of a coil with a beta sheet at the amino acid 447.

Conclusions: Early onset JOAG, with incomplete penetrance, is consistent with a novel mutation in MYOC. The finding provides pre-symptomatic molecular diagnosis for the members of this family and is useful for further genetic consultation.

Show MeSH
Related in: MedlinePlus