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Ser341Pro MYOC gene mutation in a family with primary open-angle glaucoma.

Wang F, Li Y, Lan L, Li B, Lin L, Lu X, Li J - Int. J. Mol. Med. (2015)

Bottom Line: The predicted effects of the detected variants on the secondary structure of the MYOC protein were analyzed by the Garnier-Osguthorpe-Robson method.Secondary structure prediction of p.S341P suggested that the MYOC protein was misfolded.The clinical and genetic characteristics of this mutation require further investigation.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, The First Affiliated Hospital, Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.

ABSTRACT
Glaucoma is known to induce visual impairment and blindness. The aim of the present study was to determine the clinical and genetic findings of a family with primary open-angle glaucoma (POAG). A family diagnosed with glaucoma was examined clinically and followed up for five years. Genomic DNA was extracted from the venous blood of 12 family members, and of 100 healthy individuals. The mode of inheritance was determined by the pedigree analysis. The third exon and its flanking introns of myocilin (MYOC) were amplified, and quantitative polymerase chain reaction (qPCR) products were sequenced. The restriction fragment length polymorphism analysis was performed on samples from the 12 family members and 100 normal controls. The predicted effects of the detected variants on the secondary structure of the MYOC protein were analyzed by the Garnier-Osguthorpe-Robson method. In this family, three members were diagnosed with POAG, and one member with ocular hypertension. The mode of inheritance of the family was autosomal dominant with six members being genetically affected. The heterozygous mutation was identified in the third exon of MYOC that revealed a T → C transition at position 1021 (p.S341P), which switched serine (Ser) to proline (Pro). This is a missense mutation eliminating a CviKI-1 restriction site that segregated the affected members. Secondary structure prediction of p.S341P suggested that the MYOC protein was misfolded. Ser341Pro MYOC mutation was detected in the family with POAG. The clinical and genetic characteristics of this mutation require further investigation. The mutation spectrum of MYOC may be expanded for a better diagnosis and treatment for POAG patients.

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Related in: MedlinePlus

Restriction endonuclease recognition sites. The DNA sequences, enzyme loci and restriction fragment size. The left panel shows the normal sequence of the third exon of myocilin (MYOC). The right panel shows the sequence with a T/C transition in codon 341 which changed serine (TCC) to proline (CCC), and the mutation caused the loss of restriction sites of CviKI-1 enzyme in the corresponding DNA sequence.
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f4-ijmm-35-05-1230: Restriction endonuclease recognition sites. The DNA sequences, enzyme loci and restriction fragment size. The left panel shows the normal sequence of the third exon of myocilin (MYOC). The right panel shows the sequence with a T/C transition in codon 341 which changed serine (TCC) to proline (CCC), and the mutation caused the loss of restriction sites of CviKI-1 enzyme in the corresponding DNA sequence.

Mentions: Based on the results of MYOC sequencing, we designed the relevant restriction endonuclease sites. We found that CviKI-1 can recognize c.DNA1020 on base G and c.DNA1021 on base T in the normal MYOC. The c.1021T→C (p.S341P) mutation caused loss of the restriction enzyme sites of CviKI-1 in the corresponding DNA sequence. In Table III and Fig. 4, we show the restriction endonuclease recognition sequence, enzyme loci and restriction fragment size. Loss of CviKI-1 sites was found in three POAG patients and one OHT patient, which was also identified in two members (096008 and 096009) who were not clinically diagnosed with POAG (Table II). The homologous chromosomes of family members (096002, 096003, 096005, 096006, 096008 and 096009) who had the mutation were cleaved into four fragments (257, 209, 203 and 48 bp). The homologous chromosomes of other members (096001, 096004, 096007, 096010 and 096011) were cleaved into three fragments (209, 203 and 48 bp) (Fig. 5). The three members (096006, 096008 and 096009) without POAG diagnosis at the last visit were considered to be gene mutation carriers.


Ser341Pro MYOC gene mutation in a family with primary open-angle glaucoma.

Wang F, Li Y, Lan L, Li B, Lin L, Lu X, Li J - Int. J. Mol. Med. (2015)

Restriction endonuclease recognition sites. The DNA sequences, enzyme loci and restriction fragment size. The left panel shows the normal sequence of the third exon of myocilin (MYOC). The right panel shows the sequence with a T/C transition in codon 341 which changed serine (TCC) to proline (CCC), and the mutation caused the loss of restriction sites of CviKI-1 enzyme in the corresponding DNA sequence.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4380197&req=5

f4-ijmm-35-05-1230: Restriction endonuclease recognition sites. The DNA sequences, enzyme loci and restriction fragment size. The left panel shows the normal sequence of the third exon of myocilin (MYOC). The right panel shows the sequence with a T/C transition in codon 341 which changed serine (TCC) to proline (CCC), and the mutation caused the loss of restriction sites of CviKI-1 enzyme in the corresponding DNA sequence.
Mentions: Based on the results of MYOC sequencing, we designed the relevant restriction endonuclease sites. We found that CviKI-1 can recognize c.DNA1020 on base G and c.DNA1021 on base T in the normal MYOC. The c.1021T→C (p.S341P) mutation caused loss of the restriction enzyme sites of CviKI-1 in the corresponding DNA sequence. In Table III and Fig. 4, we show the restriction endonuclease recognition sequence, enzyme loci and restriction fragment size. Loss of CviKI-1 sites was found in three POAG patients and one OHT patient, which was also identified in two members (096008 and 096009) who were not clinically diagnosed with POAG (Table II). The homologous chromosomes of family members (096002, 096003, 096005, 096006, 096008 and 096009) who had the mutation were cleaved into four fragments (257, 209, 203 and 48 bp). The homologous chromosomes of other members (096001, 096004, 096007, 096010 and 096011) were cleaved into three fragments (209, 203 and 48 bp) (Fig. 5). The three members (096006, 096008 and 096009) without POAG diagnosis at the last visit were considered to be gene mutation carriers.

Bottom Line: The predicted effects of the detected variants on the secondary structure of the MYOC protein were analyzed by the Garnier-Osguthorpe-Robson method.Secondary structure prediction of p.S341P suggested that the MYOC protein was misfolded.The clinical and genetic characteristics of this mutation require further investigation.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, The First Affiliated Hospital, Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.

ABSTRACT
Glaucoma is known to induce visual impairment and blindness. The aim of the present study was to determine the clinical and genetic findings of a family with primary open-angle glaucoma (POAG). A family diagnosed with glaucoma was examined clinically and followed up for five years. Genomic DNA was extracted from the venous blood of 12 family members, and of 100 healthy individuals. The mode of inheritance was determined by the pedigree analysis. The third exon and its flanking introns of myocilin (MYOC) were amplified, and quantitative polymerase chain reaction (qPCR) products were sequenced. The restriction fragment length polymorphism analysis was performed on samples from the 12 family members and 100 normal controls. The predicted effects of the detected variants on the secondary structure of the MYOC protein were analyzed by the Garnier-Osguthorpe-Robson method. In this family, three members were diagnosed with POAG, and one member with ocular hypertension. The mode of inheritance of the family was autosomal dominant with six members being genetically affected. The heterozygous mutation was identified in the third exon of MYOC that revealed a T → C transition at position 1021 (p.S341P), which switched serine (Ser) to proline (Pro). This is a missense mutation eliminating a CviKI-1 restriction site that segregated the affected members. Secondary structure prediction of p.S341P suggested that the MYOC protein was misfolded. Ser341Pro MYOC mutation was detected in the family with POAG. The clinical and genetic characteristics of this mutation require further investigation. The mutation spectrum of MYOC may be expanded for a better diagnosis and treatment for POAG patients.

Show MeSH
Related in: MedlinePlus