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Molecular analysis of the choroideremia gene related clinical findings in two families with choroideremia.

Lin Y, Liu X, Luo L, Qu B, Jiang S, Yang H, Liang X, Ye S, Liu Y - Mol. Vis. (2011)

Bottom Line: A novel c.1488delGinsATAAC mutation was detected in CHM in family 1.This study identified a novel mutation in CHM associated with CHM and its related clinical features.Our findings expand the genotypic spectrum of CHM mutations associated with CHM and confirm the role of Rab escort protein-1 in the pathogenesis of CHM.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

ABSTRACT

Purpose: To investigate the choroideremia (CHM) gene in two families with CHM and to characterize the related clinical features.

Methods: Two families underwent complete ophthalmic examinations and three males were diagnosed with CHM. Genomic DNA was extracted from the leukocytes of peripheral blood collected from the two families and from 100 unrelated control subjects from the same population. Exons 1-15 of CHM were amplified by PCR and directly sequenced. Ophthalmic examinations included best-corrected visual acuity, slit-lamp examination, fundus examination, visual field, optical coherence tomography, electroretinogram, and Pentacam.

Results: The affected men were hemizygous and had night blindness, chorioretinal atrophy spreading from the posterior pole to the mid-periphery, and bareness of the sclera. A novel c.1488delGinsATAAC mutation was detected in CHM in family 1. Another mutation c.1703 C>G (S558X) within exon 14 of CHM was identified in family 2, which caused the serine 558 codon (TCA) to be changed to a stop codon (TGA).

Conclusions: This study identified a novel mutation in CHM associated with CHM and its related clinical features. Our findings expand the genotypic spectrum of CHM mutations associated with CHM and confirm the role of Rab escort protein-1 in the pathogenesis of CHM.

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Related in: MedlinePlus

DNA sequence of a part of the CHM gene in the unaffected men and affected individuals. A represents normal sequence. B represents a hemizygous mutation 1488delGinsATTAC in the affected man. This mutation is predicted to truncate the 653 amino acid choroideremia (CHM) protein by 157 amino acids because of the insertion of the stop codon TAA. C represents normal sequence. D represents a C to G transversion at nucleotide 1703.
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f4: DNA sequence of a part of the CHM gene in the unaffected men and affected individuals. A represents normal sequence. B represents a hemizygous mutation 1488delGinsATTAC in the affected man. This mutation is predicted to truncate the 653 amino acid choroideremia (CHM) protein by 157 amino acids because of the insertion of the stop codon TAA. C represents normal sequence. D represents a C to G transversion at nucleotide 1703.

Mentions: Compared to the unaffected patients (Figure 4A), sequencing of the complete coding region of CHM in the affected member of family 1 showed a hemizygous mutation c.1488delGinsATTAC (Figure 4B). This mutation is predicted to truncate the 653 amino acid CHM protein by 157 amino acids. Sequencing of the complete coding region of CHM in the affected member of family 2 showed a hemizygous mutation of a C to G transversion at nucleotide 1703, changing the serine 558 codon (TCA; Figure 4C) to a stop codon (TGA; Figure 4D). The mutation c.1703 C>G (S558X) created a new restriction site for BsmAI, permitting convenient DNA-based diagnosis among the family members. This alteration is expected to result in a product that would lack the last 96 amino acids, predicting a truncated and nonfunctional REP-1. These were the only changes seen in the affected men in the two families. The alterations were not seen in 100 unrelated control subjects (200 chromosomes) from the same population, tested by bidirectional sequence analysis. No other mutations were observed in the other exons.


Molecular analysis of the choroideremia gene related clinical findings in two families with choroideremia.

Lin Y, Liu X, Luo L, Qu B, Jiang S, Yang H, Liang X, Ye S, Liu Y - Mol. Vis. (2011)

DNA sequence of a part of the CHM gene in the unaffected men and affected individuals. A represents normal sequence. B represents a hemizygous mutation 1488delGinsATTAC in the affected man. This mutation is predicted to truncate the 653 amino acid choroideremia (CHM) protein by 157 amino acids because of the insertion of the stop codon TAA. C represents normal sequence. D represents a C to G transversion at nucleotide 1703.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198496&req=5

f4: DNA sequence of a part of the CHM gene in the unaffected men and affected individuals. A represents normal sequence. B represents a hemizygous mutation 1488delGinsATTAC in the affected man. This mutation is predicted to truncate the 653 amino acid choroideremia (CHM) protein by 157 amino acids because of the insertion of the stop codon TAA. C represents normal sequence. D represents a C to G transversion at nucleotide 1703.
Mentions: Compared to the unaffected patients (Figure 4A), sequencing of the complete coding region of CHM in the affected member of family 1 showed a hemizygous mutation c.1488delGinsATTAC (Figure 4B). This mutation is predicted to truncate the 653 amino acid CHM protein by 157 amino acids. Sequencing of the complete coding region of CHM in the affected member of family 2 showed a hemizygous mutation of a C to G transversion at nucleotide 1703, changing the serine 558 codon (TCA; Figure 4C) to a stop codon (TGA; Figure 4D). The mutation c.1703 C>G (S558X) created a new restriction site for BsmAI, permitting convenient DNA-based diagnosis among the family members. This alteration is expected to result in a product that would lack the last 96 amino acids, predicting a truncated and nonfunctional REP-1. These were the only changes seen in the affected men in the two families. The alterations were not seen in 100 unrelated control subjects (200 chromosomes) from the same population, tested by bidirectional sequence analysis. No other mutations were observed in the other exons.

Bottom Line: A novel c.1488delGinsATAAC mutation was detected in CHM in family 1.This study identified a novel mutation in CHM associated with CHM and its related clinical features.Our findings expand the genotypic spectrum of CHM mutations associated with CHM and confirm the role of Rab escort protein-1 in the pathogenesis of CHM.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

ABSTRACT

Purpose: To investigate the choroideremia (CHM) gene in two families with CHM and to characterize the related clinical features.

Methods: Two families underwent complete ophthalmic examinations and three males were diagnosed with CHM. Genomic DNA was extracted from the leukocytes of peripheral blood collected from the two families and from 100 unrelated control subjects from the same population. Exons 1-15 of CHM were amplified by PCR and directly sequenced. Ophthalmic examinations included best-corrected visual acuity, slit-lamp examination, fundus examination, visual field, optical coherence tomography, electroretinogram, and Pentacam.

Results: The affected men were hemizygous and had night blindness, chorioretinal atrophy spreading from the posterior pole to the mid-periphery, and bareness of the sclera. A novel c.1488delGinsATAAC mutation was detected in CHM in family 1. Another mutation c.1703 C>G (S558X) within exon 14 of CHM was identified in family 2, which caused the serine 558 codon (TCA) to be changed to a stop codon (TGA).

Conclusions: This study identified a novel mutation in CHM associated with CHM and its related clinical features. Our findings expand the genotypic spectrum of CHM mutations associated with CHM and confirm the role of Rab escort protein-1 in the pathogenesis of CHM.

Show MeSH
Related in: MedlinePlus