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Identification of FZD4 and LRP5 mutations in 11 of 49 families with familial exudative vitreoretinopathy.

Yang H, Li S, Xiao X, Wang P, Guo X, Zhang Q - Mol. Vis. (2012)

Bottom Line: The coding exons and adjacent intronic regions of FZD4 and LRP5 were amplified with polymerase chain reaction, and the resulting amplicons were analyzed with Sanger sequencing.The phenotypes of the patients with the mutations showed great variability.Our findings provide an overview of the mutation spectrum and frequency of FZD4 and LRP5 in Chinese patients with FEVR and emphasize the complexity of FEVR mutations and phenotypes.

View Article: PubMed Central - PubMed

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

ABSTRACT

Purpose: To identify mutations in FZD4 and LRP5 in 49 Chinese families with familial exudative vitreoretinopathy (FEVR) and to reveal the mutation spectrum and frequency of these genes in the Chinese population.

Methods: Clinical data and genomic DNA were collected for patients from 49 families with FEVR. The coding exons and adjacent intronic regions of FZD4 and LRP5 were amplified with polymerase chain reaction, and the resulting amplicons were analyzed with Sanger sequencing.

Results: Eleven mutations were detected in 11 of the 49 families (22.4%), including five mutations in the FZD4 gene in six families and six mutations in the LRP5 gene in five families. Of the 11 mutations, eight were novel. Two families had the same FZD4 mutation, and one family had compound heterozygous mutations in LRP5. The phenotypes of the patients with the mutations showed great variability.

Conclusions: Our findings provide an overview of the mutation spectrum and frequency of FZD4 and LRP5 in Chinese patients with FEVR and emphasize the complexity of FEVR mutations and phenotypes.

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Related in: MedlinePlus

Protein alignment for the novel missense mutations identified in FZD4 and LRP5. Nonconserved amino acid residues are boxed. The residues with mutations are highly conserved. FZD4 orthologs included Homo sapiens (NP_036325.2), Pan troglodytes (XP_001175326.1), Mus musculus (NP_032081.2), Rattus norvegicus (NP_072145.1), Bos taurus (NP_001193198.1), Equus caballus (XP_001489854.1), Canis familiaris (XP_848753.1), Gallus gallus (NP_989430.1), and Danio rerio (XP_002664771.1). The LRP5 orthologs are from Homo sapiens (NP_002326.2), Pan troglodytes (XP_508605.2), Mus musculus (NP_032539.1), Rattus norvegicus (NP_001099791.2), Bos taurus (XP_614220.3), Gallus gallus (NP_001012915.1), and Danio rerio (NP_001170929.1).
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f3: Protein alignment for the novel missense mutations identified in FZD4 and LRP5. Nonconserved amino acid residues are boxed. The residues with mutations are highly conserved. FZD4 orthologs included Homo sapiens (NP_036325.2), Pan troglodytes (XP_001175326.1), Mus musculus (NP_032081.2), Rattus norvegicus (NP_072145.1), Bos taurus (NP_001193198.1), Equus caballus (XP_001489854.1), Canis familiaris (XP_848753.1), Gallus gallus (NP_989430.1), and Danio rerio (XP_002664771.1). The LRP5 orthologs are from Homo sapiens (NP_002326.2), Pan troglodytes (XP_508605.2), Mus musculus (NP_032539.1), Rattus norvegicus (NP_001099791.2), Bos taurus (XP_614220.3), Gallus gallus (NP_001012915.1), and Danio rerio (NP_001170929.1).

Mentions: Of the 11 mutations, seven were missense, two were nonsense, and two were frameshift deletions. The eight novel mutations were not detected in 192 chromosomes of 96 normal controls. All five novel missense changes affected evolutionarily conserved residues (Figure 3), and four of the five were predicted to be pathogenic (Table 1). The cosegregation of the mutation in additional family members who were screened is shown in Table 2.


Identification of FZD4 and LRP5 mutations in 11 of 49 families with familial exudative vitreoretinopathy.

Yang H, Li S, Xiao X, Wang P, Guo X, Zhang Q - Mol. Vis. (2012)

Protein alignment for the novel missense mutations identified in FZD4 and LRP5. Nonconserved amino acid residues are boxed. The residues with mutations are highly conserved. FZD4 orthologs included Homo sapiens (NP_036325.2), Pan troglodytes (XP_001175326.1), Mus musculus (NP_032081.2), Rattus norvegicus (NP_072145.1), Bos taurus (NP_001193198.1), Equus caballus (XP_001489854.1), Canis familiaris (XP_848753.1), Gallus gallus (NP_989430.1), and Danio rerio (XP_002664771.1). The LRP5 orthologs are from Homo sapiens (NP_002326.2), Pan troglodytes (XP_508605.2), Mus musculus (NP_032539.1), Rattus norvegicus (NP_001099791.2), Bos taurus (XP_614220.3), Gallus gallus (NP_001012915.1), and Danio rerio (NP_001170929.1).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472927&req=5

f3: Protein alignment for the novel missense mutations identified in FZD4 and LRP5. Nonconserved amino acid residues are boxed. The residues with mutations are highly conserved. FZD4 orthologs included Homo sapiens (NP_036325.2), Pan troglodytes (XP_001175326.1), Mus musculus (NP_032081.2), Rattus norvegicus (NP_072145.1), Bos taurus (NP_001193198.1), Equus caballus (XP_001489854.1), Canis familiaris (XP_848753.1), Gallus gallus (NP_989430.1), and Danio rerio (XP_002664771.1). The LRP5 orthologs are from Homo sapiens (NP_002326.2), Pan troglodytes (XP_508605.2), Mus musculus (NP_032539.1), Rattus norvegicus (NP_001099791.2), Bos taurus (XP_614220.3), Gallus gallus (NP_001012915.1), and Danio rerio (NP_001170929.1).
Mentions: Of the 11 mutations, seven were missense, two were nonsense, and two were frameshift deletions. The eight novel mutations were not detected in 192 chromosomes of 96 normal controls. All five novel missense changes affected evolutionarily conserved residues (Figure 3), and four of the five were predicted to be pathogenic (Table 1). The cosegregation of the mutation in additional family members who were screened is shown in Table 2.

Bottom Line: The coding exons and adjacent intronic regions of FZD4 and LRP5 were amplified with polymerase chain reaction, and the resulting amplicons were analyzed with Sanger sequencing.The phenotypes of the patients with the mutations showed great variability.Our findings provide an overview of the mutation spectrum and frequency of FZD4 and LRP5 in Chinese patients with FEVR and emphasize the complexity of FEVR mutations and phenotypes.

View Article: PubMed Central - PubMed

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

ABSTRACT

Purpose: To identify mutations in FZD4 and LRP5 in 49 Chinese families with familial exudative vitreoretinopathy (FEVR) and to reveal the mutation spectrum and frequency of these genes in the Chinese population.

Methods: Clinical data and genomic DNA were collected for patients from 49 families with FEVR. The coding exons and adjacent intronic regions of FZD4 and LRP5 were amplified with polymerase chain reaction, and the resulting amplicons were analyzed with Sanger sequencing.

Results: Eleven mutations were detected in 11 of the 49 families (22.4%), including five mutations in the FZD4 gene in six families and six mutations in the LRP5 gene in five families. Of the 11 mutations, eight were novel. Two families had the same FZD4 mutation, and one family had compound heterozygous mutations in LRP5. The phenotypes of the patients with the mutations showed great variability.

Conclusions: Our findings provide an overview of the mutation spectrum and frequency of FZD4 and LRP5 in Chinese patients with FEVR and emphasize the complexity of FEVR mutations and phenotypes.

Show MeSH
Related in: MedlinePlus