Screening of the LTBP2 gene in 214 Chinese sporadic CYP1B1-negative patients with primary congenital glaucoma.
OBJECTIVE
To identify deleterious mutations in the latent transforming growth factor-β-binding protein 2 (LTBP2) gene in sporadic patients with primary congenital glaucoma (PCG) from a Han Chinese population, which had been excluded for mutations in the CYP1B1 gene.


METHODS
In this retrospective case-control study, 36 coding exons and adjacent exon-intron boundaries of LTBP2 were amplified with PCR and screened for mutations with Sanger sequencing in DNA samples of 214 sporadic patients with PCG. Sequence variants identified in the patients with PCG were subsequently screened in 100 unaffected control subjects and the unaffected parents of the patients with PCG who had sequence changes in LTBP2.


RESULTS
Eight heterozygous single nucleotide polymorphisms (SNPs) in coding regions of LTBP2 were identified in the patients with PCG. Four of these SNPs were missense changes that resulted in the replacement of amino acids (rs2304707, rs116914994, rs45468895, and rs763035721), two of which (rs2304707 and rs116914994) were also present in the control subjects. No significant differences in the frequencies of the missense SNPs were found between the patients with PCG and the controls. The two missense SNPs, rs45468895 and rs763035721, which were each found in one patient also existed in their unaffected parents, suggesting that these two SNPs were not segregated in these families and are unlikely to be a disease-causative variant. In addition, four synonymous SNPs were detected in the patients with PCG (rs61738025, rs862031, rs199805158, and rs12586758).


CONCLUSIONS
The results showed that no deleterious mutations were found in coding regions of LTBP2 in patients with PCG, suggesting that it is not a causal gene for PCG in the Han Chinese population.
Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Xueli
X
Chen
Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Yuhong
Y
Chen
Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA.
Bao Jian
BJ
Fan
Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences, Fudan University, Shanghai, China.
Mingying
M
Xia
Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Li
L
Wang
Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China; State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China; Key Laboratory of Myopia, Ministry of Health (Fudan University), and Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai, China.
Xinghuai
X
Sun
D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005784:Gene Amplification; D006801:Humans; D006871:Hydrophthalmos / Q000175:diagnosis / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D053779:Latent TGF-beta Binding Proteins / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies
D017931:DNA Primers; C509035:LTBP2 protein, human; D053779:Latent TGF-beta Binding Proteins; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1