OBJECTIVE: To analyze genetic variant in a pedigree affected with congenital high myopia. METHODS: Whole exome sequencing (WES) was carried out for the proband. Suspected variation was verified with Sanger sequencing. The pedigree was also subjected to co-segregation analysis. RESULTS: WES has identified a novel splice site heterozygous variant (c.2556+1G>A) in the COL11A1 gene in the proband. Co-segregation analysis of the pedigree showed that the affected mother and two daughters of the proband have carried the same variant(c.2556+1G>A), while his unaffected father and sister did not. Based on the ACMG Standards and Guidelines for the Interpretation of Sequence Variants, the variant was classified as "likely pathogenic" (PVS1+PM2). CONCLUSION A novel splice variant (c.2556+1G>A) of the COL11A1 gene has been identified in a pedigree affected with congenital high myopia, which probably underlies the disease.
Collagen Type XI ; genetics ; Genetic Testing ; Heterozygote ; Humans ; Myopia ; genetics ; Pedigree ; Whole Exome Sequencing

Myopia is an important cause of blindness, in which an image is focused in front of the retina. Genetic factors have been implicated in the pathogenesis of myopia. Based on the molecular genetic study, some genetic loci linked to myopia have been mapped, but no disease-causing gene has been identified. Here authors review the genetic study on myopia, including gene mapping and candidate gene screening.
Animals ; Chromosome Mapping ; Chromosomes, Human ; genetics ; Genetic Testing ; Humans ; Myopia ; genetics

OBJECTIVETo analyze the mutation of COL9A2 gene and investigate the molecular pathogenesis of pathological myopia in a Han Chinese population.

METHODSMutation in the coding region of the COL9A2 gene was screened by Sanger sequencing in 200 subjects with pathological myopia and 200 normal controls. The detected variants were genotyped by SNaPshot method in another 200 myopic cases and 200 normal controls.

RESULTSSanger sequencing has failed to detect the reported D281fs frameshift mutation in the 200 cases. A novel variant, c.143G>C heterozygous missense mutation in exon 2, was identified in a myopic subject, and another novel variant, c.884G>A heterozygous missense mutation in exon 17, was found in another case. Neither was found in normal controls. One SNP (rs2228564) was detected in the coding region of the COL9A2 gene, but there was no significant difference in its allelic frequencies between the two groups (P> 0.05). Genotyping of the remainder 200 cases and 200 controls by SNaPshot method has found a c.143G>C in 1 case and c.884G>A in 2 cases, though no significant difference between the two groups was detected (P> 0.05).

CONCLUSIONThe D281fs frameshift mutation in the COL9A2 gene is not associated with pathological myopia in the studied Han Chinese population. Two novel mutations, c.143G>C in exon 2 and c.884G>A in exon 17 of the COL9A2 gene, may contribute to the development of pathological myopia.

Asian Continental Ancestry Group ; genetics ; China ; ethnology ; Collagen Type IX ; genetics ; Frameshift Mutation ; Humans ; Myopia, Degenerative ; genetics ; Sequence Analysis, DNA

OBJECTIVE: To investigate the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Cohen syndrome. METHODS: A proband who was admitted to Zhengzhou People's Hospital on June 2, 2021 due to intellectual disability and developmental delay, in addition with her younger sister and other family members, were selected as the study subjects. Clinical data of the proband and her younger sister were collected. Genomic DNA was extracted from peripheral venous blood and chorionic villi samples. Chromosomal abnormalities were detected with chromosomal microarray analysis (CMA). Whole exome sequencing (WES) and Sanger sequencing were carried out to detect candidate variants in the proband. With RNA extracted from the peripheral blood samples, VPS13B gene transcripts and expression were analyzed by PCR and real-time quantitative PCR. Prenatal diagnosis was carried out at 12 weeks' gestation. RESULTS: The proband was a 10-year-old female with clinical manifestations including development delay, obesity, severe myopia and peculiar facial features. Her sister was 3 years old with a similar phenotype. CMA revealed no chromosomal abnormality in the proband, while WES results revealed that the proband and her sister had both harbored compound heterozygous variants of the VPS13B gene, namely c.10076_10077delCA (p.T3359fs*29) and c.6940+1G>T, which were respectively inherited from their mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+PS4+PM4+PP1; PVS1+PM2_Supporting+PM3+PP1). In vivo splicing assay confirmed that the c.6940+1G>T variant has produced a frameshift transcript with skipping of exon 38. Compared with the control group, the expression of RNA in the peripheral blood of the proband's parents has decreased to 65% ~ 70% (P < 0.01), whilst that in the proband and her sister has decreased to 40% (P < 0.001). Prenatal diagnosis at 12 weeks of gestation has found that the fetus only harbored the heterozygous c.10076_ 10077delCA variant. CONCLUSION The c.10076_10077delCA (p.T3359fs*29) frameshift variant and c.6940+1G>T splicing variant probably underlay the Cohen syndrome in this pedigree. Genetic testing has facilitated the diagnosis of this disease.
Female ; Humans ; East Asian People ; Intellectual Disability/genetics* ; Mutation ; Myopia/genetics* ; Pedigree ; Vesicular Transport Proteins/genetics* ; Child, Preschool ; Child

We report a case of one sister and brother with mirror image myopic anisometropia. One sister and brother complained visual disturbance. The sister was 10 years 11 months old, and brother was 8 years 4 months old. Full ophthalmic examinations were performed, including slit lamp examination, intraocular pressure, keratometry, anterior chamber depth, axial length, fundus examination and the cycloplegic refraction. The cycloplegic refractive power was -15.50 dpt cyl.+4.50 dpt Ax 85degrees (right eye), -1.00 dpt cyl.+0.50 dpt Ax 90degrees (left eye) in the sister; -1.75 dpt cyl.+2.25 dpt Ax 90degrees (right eye), -9.50 dpt cyl.+4.00 dpt Ax 80degrees (left eye) in the brother. The co-occurrence of severe myopic anisometropia in a sister and brother is extremely rare. The present case suggests that severe myopic anisometropia may be related by genetic inheritance.
Anisometropia/*etiology/*genetics/physiopathology/therapy ; Child ; Female ; Humans ; Male ; Myopia/*complications/*genetics/physiopathology/therapy ; Refraction, Ocular ; *Siblings ; Visual Acuity

OBJECTIVETo investigate the expression of 5 muscarinic receptor subtypes in the scleral tissue of immature guinea pigs.

METHODSThe scleral tissue was collected from six 2-week-old pigmented guinea pigs to determine mRNA expressions of the muscarinic receptors with RT-PCR. Immunofluorescence was used to observe the protein expressions of the 5 muscarinic receptor subtypes.

RESULTSThe mRNAs of the 5 muscarinic receptor subtypes were all detected in the scleral tissue, and the mRNA expression was the highest for M1 subtype. Green fluorescence of M1 to M5 subtypes surrounding the fibroblast nuclei were found in the scleral matrix using laser confocal microscopy.

CONCLUSIONFive muscarinic receptor subtypes are present in the scleral tissues of immature guinea pigs, indicating the involvement of the muscarinic receptors in eye growth regulation.

Animals ; Female ; Gene Expression Regulation ; Guinea Pigs ; Immunohistochemistry ; Male ; Myopia ; metabolism ; pathology ; RNA, Messenger ; genetics ; metabolism ; Receptors, Muscarinic ; genetics ; metabolism ; Sclera ; cytology ; metabolism

OBJECTIVE: To investigate the effect of regulation of VIPhybrid, an unselective antagonist of vasoactive intestinal peptide receptors (VIPR), on the formation and development of form deprivation myopia (FDM) in chick and the expression of protein and mRNA of VIP on the retina and choroids of in chicks. METHODS: Seventy-two 1-day-old yellow healthy leghorn chicks were assigned into 6 groups (12 in each group). Eyes in Group I were covered on the right as a blank control group. Eyes in GroupII were those eyes having been injected with 20 microL saline into vitreous cavity and then covered as a negative control group. Eyes in GroupIII,IV and V were injected with 20 microL VIPhybrid with low (3*10(-12) mol/L), middle (3*10(-10) mol/L) and high (3*10(-8) mol/L) dosage into vitreous cavity and then covered as experimental groups. The above groups had been continuously covered for 1 week. Eyes in Group VI were uncovered and uninjected as a normal control group. Diopter was detected using retinoscopic refraction. The eyeball axis was determined using ophthalmological ultra-A. The expression of protein and mRNA of VIP on retina-choroids-sclera were investigated by SP immunohistochemistry staining and RT-PCR. RESULTS: Form deprivation for 1 week induced high myopia eyes and elongated eyeball axis in GroupI and GroupII, and there was no difference between the 2 groups (P>0.05). The diopter and eyeball axis were significantly reduced in Group III, IV, and V as compared with Group I and II (P<0.01), but the diopter was higher and the eyeball axis was longer than those of Group VI. The diopter and eyeball axis had negative correlation with the concentration gradient of VIPhybrid. The expressions of protein and mRNA of VIP in Group III, IV, and V were down-regulated as compared with those of Group I and I I(P<0.01)and also down-regulated with the increase of concentration of VIPhybrid. CONCLUSION VIPhybrid can decrease the development of FDM in chicks, which may provide a new pathway for drug therapy of myopia in human beings.
Animals ; Animals, Newborn ; Chickens ; Myopia ; etiology ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Receptors, Vasoactive Intestinal Peptide ; antagonists & inhibitors ; Recombinant Fusion Proteins ; pharmacology ; Retina ; metabolism ; Vasoactive Intestinal Peptide ; biosynthesis ; genetics

OBJECTIVETo screen the variations of TG interacting factor(TGIF) gene in encoding sequence in Chinese high myopia patients and normal controls and to analyze the SNPs of TGIF gene encoding sequence in Chinese population.

METHODSGenomic DNA was collected from 204 probands with high myopia and 112 unrelated persons without high myopia. The coding sequences of TGIF gene in 316 subjects were analyzed by using exon-by-exon PCR heteroduplex-SSCP analysis and sequencing.

RESULTSThere were 3 types of SNP and one single nucleotide mutation in the coding sequence of TGIF gene: IVS-2 nt350 G --> T(36/204), codon140 CCA --> CCG; Pro140Pro codon163 CCG --> CTG;Pro163Leu and codon126 GTG --> GCG; Val126Ala(1/204). The SNPs of codon140 CCA --> CCG and codon163 CCG --> CTG were composed of 3 alleles and 5 genotypes in Chinese population which abide by Hardy-Weinberg law.

CONCLUSIONThere was no evidence to prove that mutations in the TGIF gene are responsible for the high myopia in Chinese. Three SNPs of coding sequence TGIF gene in Chinese population abide by Hardy-Weinberg law.

China ; DNA ; chemistry ; genetics ; DNA Mutational Analysis ; Gene Frequency ; Homeodomain Proteins ; genetics ; Humans ; Mutation ; Myopia ; genetics ; pathology ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Polymorphism, Single-Stranded Conformational ; Repressor Proteins ; genetics

BACKGROUNDDevelopment of myopia among young children is often contributed to the refractive status of the parents. This study was conducted to determine whether myopia can be inherited across the generation among a sample in the Klang Valley. Three generations involved are: G1 (grandparents), G2 (parents) and G3 (children).

METHODSSixty-two families were screened and forty families were selected to participate in this study. The inclusion criterion is having at least one myopic member in any of the three generations. Subjects (G2) were first asked to fill up a questionnaire form before their refractive status was determined by clinical examination that provided acuity of 6/6 or better. Refractive status of G1 was determined using information from the questionnaire while for G2 and G3 through clinical examination.

RESULTSGenerally, the prevalence of myopia is seen to increase throughout the generations from G1 being the lowest (25.6%) to G3 being the highest (41.1%). Strong genetic influence can be found between G1 and G2 as majority of myopes in G2 is when both parents were myopic. However, although the prevalence of myopia increased from G2 to G3, there was no strong genetical influence. Majority of subjects in G3 were non-myopes when both their parents were myopic.

CONCLUSIONParental history accounts for a limited proportion of variance in myopia development.

Adolescent ; Adult ; Aged ; Family Health ; Female ; Humans ; Malaysia ; epidemiology ; Male ; Middle Aged ; Myopia ; epidemiology ; genetics ; Retrospective Studies ; Surveys and Questionnaires ; Young Adult

OBJECTIVE: To investigate the dynamic expression and significance of vasoactive intestinal peptide receptor 2 (VIPR2) on retina-choroid-clera in high myopia. METHODS: Twenty-one yellow chicks of 1 day old were used in the research. The right eyes were the experimental group, covered continuously for 1 week, 2 weeks and 4 weeks respectively. The left eyes were not covered as the normal control group. Both groups were detected diopter degrees using retinoscopic refraction, determinated eyeball axis using ophthalmology ultra-A, and investigated VIPR2 expression on retina-choroid-sclera in both groups at three stages by SP immunohistochemical staining. RESULTS: The experimental eyes changed from hypermetropia at pre-experiment to high myopia during the experiment stages, and the diopter degrees were deeper and eyeball axis was longer along with the period of being covered. Both groups had strong expression of VIPR2 on photoreceptor-outer segment of the retina and choroids. The expression was down-regulated with the time in both groups. Compared with the control group, VIPR2 expression of the experimental group was significantly up-regulated (P < 0.05). CONCLUSION Form deprivation could induce high myopia. The expression of VIPR2 existed on photoreceptor-outer segment of the retina and choroids. VIPR2 may play an important role on the formation and development of myopia.
Animals ; Animals, Newborn ; Chickens ; Choroid ; metabolism ; Female ; Male ; Myopia ; etiology ; metabolism ; Receptors, Vasoactive Intestinal Peptide, Type II ; biosynthesis ; genetics ; Retina ; metabolism