OBJECTIVE: To explore the clinical characteristics and genetic basis of two Chinese pedigrees affected with Joubert syndrome. METHODS: Clinical data of the two pedigrees was collected. Genomic DNA was extracted from peripheral blood samples and subjected to high-throughput sequencing. Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was carried out for a high-risk fetus from pedigree 2. RESULTS: The proband of pedigree 1 was a fetus at 23⁺⁵ weeks gestation, for which both ultrasound and MRI showed "cerebellar vermis malformation" and "molar tooth sign". No apparent abnormality was noted in the fetus after elected abortion. The fetus was found to harbor c.812+3G>T and c.1828G>C compound heterozygous variants of the INPP5E gene, which have been associated with Joubert syndrome type 1. The proband from pedigree 2 had growth retardation, mental deficiency, peculiar facial features, low muscle tone and postaxial polydactyly of right foot. MRI also revealed "cerebellar dysplasia" and "molar tooth sign". The proband was found to harbor c.485C>G and c.1878+1G>A compound heterozygous variants of the ARMC9 gene, which have been associated with Joubert syndrome type 30. Prenatal diagnosis found that the fetus only carried the c.485C>G variant. A healthy infant was born, and no anomalies was found during the follow-up. CONCLUSION The compound heterozygous variants of the INPP5E and ARMC9 genes probably underlay the disease in the two pedigrees. Above finding has expanded the spectrum of pathogenic variants underlying Joubert syndrome and provided a basis for genetic counseling and prenatal diagnosis.
Female ; Humans ; Pregnancy ; Pedigree ; Cerebellum/abnormalities* ; Abnormalities, Multiple/diagnosis* ; Eye Abnormalities/diagnosis* ; Kidney Diseases, Cystic/diagnosis* ; Phosphoric Monoester Hydrolases/genetics* ; Retina/abnormalities* ; East Asian People ; Mutation

OBJECTIVE: To identify pathogenic variants in two families with patients suspected for Joubert syndrome(UBST) by cerebellar vermis hypoplasia. METHODS: Clinical data and peripheral venous blood and skin tissue samples were collected for the extraction of genomic DNA. Potential variants were screened by using targeted capture and next generation sequencing. Suspected variants were validated by PCR and Sanger sequencing. The frequency of the variants in the population was calculated. Pathogenicity of the variants was predicted by following the guidelines of the American College of Medical Genetics and Genomics (ACMG). Prenatal diagnosis was provided to these families upon subsequent pregnancy. RESULTS: The proband of family 1 was found to harbor homozygous c.2072delT (p.F691S*fs19) frameshift variant of the AHI1 gene, which may cause premature termination of translation of the Abelson helper integration site 1 after the 691st amino acid. The proband of family 2 was found to harbor compound heterozygous variants of the CPLANE1 gene, namely c.7243dupA (p.T2415Nfs*7) and c.8001delG (p.K2667Nfs*31), which can respectively lead to premature termination of translation of ciliogenesis and planar polarity effector 1 after the 2145th and 2667th amino acids. All of the three variants were previously unreported, and were predicted to be pathogenic by bioinformatic analysis. CONCLUSION The AHI1 c.2072delT and CPLANE1 c.7243dupA and c.8001delG variants probably underlay JBTS3 in family 1 and JBTS17 in family 2, respectively. Based on above results, prenatal diagnosis may be offered to the affected families upon their subsequent pregnancies.
Abnormalities, Multiple ; diagnosis ; genetics ; Adaptor Proteins, Vesicular Transport ; genetics ; Cerebellum ; abnormalities ; Eye Abnormalities ; diagnosis ; genetics ; Female ; Genetic Testing ; Genetic Variation ; Humans ; Kidney Diseases, Cystic ; diagnosis ; genetics ; Membrane Proteins ; genetics ; Mutation ; Pregnancy ; Prenatal Diagnosis ; Retina ; abnormalities

OBJECTIVE: To explore the pathogenesis of two fetuses from one family affected with Joubert syndrome (JS). METHODS: Whole exome sequencing was employed to screen potential mutations in both fetuses. Suspected mutations were verified by Sanger sequencing. Impact of intronic mutations on DNA transcription was validated by cDNA analysis. RESULTS: Two novel TCTN1 mutations, c.342-8A>G and c.1494+1G>A, were identified in exons 2 and 12, respectively.cDNA analysis confirmed the pathogenic nature of both mutations with interference of normal splicing resulting in production of truncated proteins. CONCLUSION The genetic etiology of the family affected with JS has been identified.Above findings have enriched the mutation spectrum of TCTN1gene and facilitated understanding of the genotype-phenotype correlation of JS.
Abnormalities, Multiple ; diagnosis ; genetics ; Cerebellum ; abnormalities ; Eye Abnormalities ; diagnosis ; genetics ; Humans ; Kidney Diseases, Cystic ; diagnosis ; genetics ; Membrane Proteins ; genetics ; Mutation ; Pedigree ; Retina ; abnormalities ; Whole Exome Sequencing

OBJECTIVE: To detect mutation of NDP gene in a pedigree affected with Norrie disease. METHODS: Sanger sequencing was used to analyze the NDP gene at Xp11.3. Prenatal diagnosis was performed on amniotic fluid sample after the causative gene was detected. RESULTS: Sanger sequencing has revealed a c.2T>C (p.M1T) missense mutation of the NDP gene in the proband and the fetus. The same variation was not found in ClinVar and HGMD database. CONCLUSION The c.2T>C mutation of the NDP gene probably underlies the Norrie disease in this pedigree.
Blindness ; congenital ; Eye Proteins ; Female ; Genetic Diseases, X-Linked ; Humans ; Nerve Tissue Proteins ; Nervous System Diseases ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Retinal Degeneration ; Spasms, Infantile

OBJECTIVETo explore the genetic etiology of a pedigree affected with hereditary retinitis pigmentosa.

METHODSHigh-throughput DNA sequencing was used to analyze the sequences of 173 genes associated with hereditary eye diseases in the proband. Suspected mutation was verified with PCR amplification and Sanger sequencing.

RESULTSThe proband was found to have carried a c.570_571 ins GAAGATGCTGT insertional mutation in the RP2 gene located on the X chromosome. All female carriers of the pedigree were heterozygous, while all affected males were hemizygous for the same mutation.

CONCLUSIONThe inheritance pattern of this retinitis pigmentosa pedigree was X-linked recessive. The c.570_571 ins GAAGATGCTGT insertional mutation of the RP2 gene probably underlies the disease.

Eye Proteins ; genetics ; Female ; Genetic Diseases, X-Linked ; genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Male ; Membrane Proteins ; genetics ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Retinitis Pigmentosa ; genetics

PURPOSE: Age-related eye disease is often considered part of natural aging. Lack of awareness of eye conditions can result in missed treatment. We investigated the rates of awareness of cataract and age-related macular degeneration, the most common age-related eye-diseases, and the associated factors among elderly Koreans. METHODS: We identified 7,403 study subjects (≥40 years old) with cataract or age-related macular degeneration based on ophthalmic examination results during the 5th Korean National Health and Nutrition Examination Survey conducted between 2010 and 2012. We assessed whether patients were aware of their eye condition based on a previous diagnosis by a physician. RESULTS: The average awareness rate over the 3-year study period was 23.69% in subjects with cataract and 1.45% in subjects with age-related macular degeneration. Logistic regression analysis showed that patients with cataract were more likely to recognize their condition if they had myopia (odds ratio, 2.08), hyperopia (odds ratio, 1.33), family history of eye disease (odds ratio, 1.44), or a past eye examination (odds ratio, 4.07-29.10). The presence of diabetes mellitus was also a significant predictor of patient awareness of cataract (odds ratio, 1.88). CONCLUSIONS: Poor patient recognition of eye disease among the Korean elderly highlights the seriousness of this potential public health problem in our aging society. Pre-existing eye-related conditions and diabetes were significant predictors of awareness; therefore, patients in frequent contact with their doctors have a greater chance of detecting eye disease.
Aged* ; Aging ; Cataract* ; Diabetes Mellitus ; Diagnosis ; Eye Diseases ; Humans ; Hyperopia ; Logistic Models ; Macular Degeneration* ; Myopia ; Nutrition Surveys ; Public Health

PURPOSE: The purpose of our study was to evaluate the cause of acquired third, fourth, and sixth nerve palsy while also establishing recovery rates and important factors for recovery. METHODS: A retrospective chart review was performed for 92 patients who visited the ophthalmologic department of Konyang University Hospital with acquired third, fourth, and sixth nerve palsy from March 2015 to February 2016. Recovery rates and factors for recovery were evaluated in only 66 patients who received first ocular exam within 2 weeks of onset and who were followed up for at least 6 months. Complete recovery was defined as both complete recovery of the angle of deviation and the restoration of eye movement in all directions. For the degree of ocular motor restriction, −4 was defined as not crossing the midline and −2 was defined as 50% eye movement. The degree of ocular motor restriction was analyzed from −1/2 to 4. RESULTS: The fourth nerve was affected most frequently (n = 37, 40.2%), followed by the sixth cranial nerve (n = 33, 35.9%), the third cranial nerve (n = 18, 19.6%), and a combination of 2 or more cranial nerves (n = 4, 4.3%). Vasculopathy (n = 44, 47.8%) was the most common etiology, followed by trauma (n = 14, 15.2%), idiopathic (n = 13, 14.1%), inflammation(n = 10, 10.9%), neoplasm (n = 9, 9.8%), and aneurysm (n = 2, 2.2%). Complete recovery rate occurred for 66.7% (n = 44) of patients, and the overall recovery rate (i.e., at least partial recovery) was 86.3% (n = 57). Significant factors for complete recovery were the initial deviation angle and the limitation of extraocular movement (p < 0.001, p = 0.005, respectively, according to univariate analysis). CONCLUSIONS: In this study, paralytic strabismus due to vasculopathy was the most common etiology, and a lower degree of initial deviation resulted in an improved complete recovery rate. In addition, a high overall recovery rate was possible through quick diagnosis and early treatment of cranial nerve palsy.
Abducens Nerve ; Abducens Nerve Diseases ; Aneurysm ; Cranial Nerve Diseases ; Cranial Nerves ; Diagnosis ; Eye Movements ; Humans ; Oculomotor Nerve ; Retrospective Studies ; Strabismus*

Rheumatic diseases are associated various extra-articular manifestations, such as eye, nerve, pericardium, and pleura. The anterior part of the eye has distinguished anatomic structure resembling synovial joints, thus it is a common site of ocular manifestation in rheumatic disease. These changes include sicca syndrome, peripheral ulcerative keratitis, episcleritis, scleritis, and iritis. Some of these findings may be the clues for the diagnosis of the rheumatic diseases, and some ocular manifestations may represent the activity or prognosis of the rheumatic diseases. These ocular complications may leads to severe visual loss. It is crucial to rule out underlying systemic diagnosis in rheumatic disease associated ocular diseases, and when diagnosed, the coordination of the rheumatologist with the ophthalmologist in the treatment is imperative.
Corneal Ulcer ; Diagnosis ; Eye Diseases* ; Iritis ; Joints ; Pericardium ; Pleura ; Prognosis ; Rheumatic Diseases* ; Scleritis ; Sjogren's Syndrome

BACKGROUNDDry eye patients suffer from all kinds of symptoms. Sometimes, the clinical signs evaluation does not disclose any obvious difference in routine examination; in vivo confocal microscopy (IVCM) is a powerful tool for ocular surface disease. This study aimed to clarify meibomian gland (MG) alterations in dry eye patients with different symptoms and to compare the findings using IVCM.

METHODSA total of sixty patients were recruited, all subjected to Ocular Surface Disease Index (OSDI) and Salisbury Eye Evaluation Questionnaire (SEEQ), and questionnaires for the assessment of dry eye symptoms before clinical sign examinations were given to the patients. Finally, IVCM was applied to observe MG's structure. Statistical analysis was performed using the t-test, Mann-Whitney U-test and Spearman correlation analysis. The differences were statistically significant when P< 0.05.

RESULTSIn the severe symptom group, OSDI and SEEQ scores were significantly higher (P< 0.05) compared with the mild symptoms group. All other clinical sign examinations had no statistical difference in the two groups (P> 0.05). However, all the IVCM-observed data showed that patients with severe symptoms had more significant fibrosis in MG (acinar unit area 691.87 ± 182.01 μm2 for the severe, 992.17 ± 170.84 μm2 for the mild; P< 0.05) and severer decrease in the size of MG acinar units than those observed in patients with mild symptoms (MG acinar unit density [MGAUD] 70.08 ± 18.78 glands/mm2, MG acinar unit longest diameter [MGALD] 51.50 ± 15.51 μm, MG acinar unit shortest diameter [MGASD] 20.30 ± 11.85 μm for the severe, MGAUD 89.53 ± 39.88 glands/mm2, MGALD 81.57 ± 21.14 μm, MGASD 42.37 ± 14.55 μm for the mild;P< 0.05). Dry eye symptoms were negatively correlated with MG confocal microscopic parameters and positively correlated with conjunctival inflammatory cells and Langerhans cells (P< 0.05).

CONCLUSIONSIVCM application provides a strong support to differentiate dry eye patients with different symptoms: meibomian gland dysfunction (MGD) plays a pivotal role in dry eye aggravation, and using IVCM to observe MG fibrosis, changes in size and density of MG as well as status of inflammation cells can help not only correctly diagnose the type and severity of dry eye, but also possibly prognosticate in routine eye examination in the occurrence of MGD.

Adult ; Aged ; Dry Eye Syndromes ; diagnosis ; physiopathology ; Eyelid Diseases ; diagnosis ; physiopathology ; Female ; Humans ; Male ; Meibomian Glands ; pathology ; physiopathology ; Microscopy, Confocal ; methods ; Middle Aged

Hereditary vitreous degeneration muddy is rare in clinic. Here we report ten cases (thirteen eyes) of hereditary vitreous degeneration muddy from two families. All patients presented with vitreous opacity, and the textures appeared tough and tensile. Two cases had concurrent detachment of rhegmatogenous retina. HE staining showed red changeableness, and methyl violet staining appeared purple. All patients received vitrectomy with traditional Chinese medicine treatment, and got satisfactory efficacy.
Eye Diseases, Hereditary ; diagnosis ; pathology ; surgery ; therapy ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Retinal Detachment ; diagnosis ; surgery ; Vitrectomy ; Vitreous Body ; pathology ; surgery