Bardet-Biedl syndrome (BBS) is a rare ciliopathy generally inherited with an autosomal recessive pattern. BBS is characterized by 6 primary features namely retinal dystrophy, obesity, postaxial polydactyly, renal dysfunction, learning difficulties, and hypogonadism and a wide range of secondary features. To date, mutations in 16 genes have been identified as causative factors for BBS. Among them, the BBS1 and BBS10 genes are major disease-causing genes, and each of these gene mutations presents in more than 20% of all BBS patients. Genotype-phenotype correlations have not been observed in BBS, and there can be phenotypic overlap between BBS and other ciliopathies. In Korea, no molecular, genetically confirmed case of BBS has been reported to date. Herein, we describe the case of the first Korean siblings with BBS resulting from 2 BBS10 gene mutations who showed typical clinical phenotypes, including retinal dystrophy, obesity, intellectual disability, cystic tubular disease, and postaxial polydactyly.
Bardet-Biedl Syndrome* ; Genetic Association Studies ; Humans ; Hypogonadism ; Intellectual Disability ; Korea ; Learning ; Obesity ; Phenotype ; Polycystic Kidney Diseases ; Polydactyly ; Retinal Dystrophies ; Retinitis Pigmentosa ; Siblings*

There are several diseases characterized by neurologic abnormalities and renal disease. Joubert syndrome is one of them. Joubert syndrome is a relatively rare autosomal recessive syndrome. The most significant and constant neurologic finding is hypoplasia of the cerebellar vermis. Joubert syndrome is associated with hypotonia, retinal dystrophy, abnormal eye movement, delayed development, abnormal respiratory pattern (neonatal episodic tachypnea or apnea) and nephronophthisis. We report a boy with Joubert syndrome associated with nephrocalcinosis and agenesis of the cerebellar vermis. This patient had also abnormal eye movement, hypotonia, abnormal respiratory pattern, delayed development and chronic renal failure.
Eye Movements ; Humans ; Kidney Failure, Chronic ; Male ; Muscle Hypotonia ; Nephrocalcinosis* ; Neurologic Manifestations ; Retinal Dystrophies ; Tachypnea

OBJECTIVE: To evaluate and compare whole exome sequencing (WES) and targeted panel sequencing in the clinical molecular diagnosis of the Chinese families affected with inherited retinal dystrophies (IRDs). METHODS: The clinical information of 182 probands affected with IRDs was collected, including their family history and the ophthalmic examination results. Blood samples of all probands and their relatives were collected and genomic DNA was extracted by standard protocols. The first 91 cases were subjected to the WES and the other 91 cases were subjected to a specific hereditary eye disease enrichment panel (HEDEP) designed by us. All likely pathogenic and pathogenic variants in the candidate genes were determined by Sanger sequencing and co-segregation analyses were performed in available family members. Copy number variations (CNVs) detected by HEDEP were further validated by multiplex ligation-dependent probe amplification (MLPA). As PRGR ORF15 was difficult to capture by next generation sequencing (NGS), all the samples were subjected to Sanger sequencing for this region. All sequence changes identified by NGS were classified according to the American College of Medical Gene-tics and Genomics and the Association for Molecular Pathology (ACMG/AMP) variant interpretation guidelines. In this study, only variants identified as pathogenic or likely pathogenic were included, while those variants of uncertain significance, likely benign or benign were not included. RESULTS: In 91 cases with WES, pathogenic or likely pathogenic variants were determined in 30 cases, obtaining a detection rate of 33.00% (30/91); While in 91 cases with HEDEP sequencing, pathogenic or likely pathogenic variants were determined in 51 cases, achieving the diagnostic rate of 56.04% (51/91), and totally, the diagnostic rate was 44.51%. HEDEP had better sequencing coverage and read depth than WES, therefore HEDEP had higher detection rate. In addition, HEDEP could detect CNVs. In this study, we detected disease-causing variants in 29 distinct IRD-associated genes, USH2A, ABCA4 and RPGR were the three most common disease-causing genes, and the frequency of these genes in Chinese IRDs population was 11.54% (21/182), 6.59% (12/182) and 3.85% (7/182), respectively. We found 43 novel variants and 6 cases carried variants in RPGR ORF15. CONCLUSION NGS in conjunction with Sanger sequencing offers a reliable and effective approach for the genetic diagnosis of IRDs, and after evaluating the pros and cons of the two sequencing methods, we conclude that HEDEP should be used as a first-tier test for IRDs patients, WES can be used as a supplementary molecular diagnostic method due to its merit of detecting novel IRD-associated genes if HEDEP or other methods could not detect disease-causing va-riants in reported genes. In addition, our results enriched the mutational spectra of IRDs genes, and our methods paves the way of genetic counselling, family planning and up-coming gene-based therapies for these families.
DNA Copy Number Variations ; Humans ; Mutation ; Pedigree ; Retinal Dystrophies/genetics* ; Whole Exome Sequencing

Joubert syndrome is the very rare autosomal recessive disorder which is including agenesis of cerebellar vermis, respiratory discomfort, ocular motor apraxia, hereditary retinal dystrophy, ataxia and developmental retardation. To diagnose, the findings of electroretinography and visual evoked potential study can be useful and hypoplasia of cerebellar vermis in brain MRI can make certain diagnosis. We found ocular motor apraxia without head thrusts in 4-month little baby can't even control his head and neck, and then his electroretinography and visual evoked potential study was normal and there was agenesis of cerebellar vermis by MRI finding. So he was diagnosed as Joubert syndrome with ocular motor apraxia. Agenesis of cerebellar vermis is considered to be one of the causes of oculomotor apraxia, and the clinical presentation varies with the age and motor development of the child. So, we describe this case with a brief review of the literatures related to this disease.
Apraxias* ; Ataxia ; Brain ; Child ; Diagnosis ; Electroretinography ; Evoked Potentials, Visual ; Head* ; Humans ; Magnetic Resonance Imaging ; Neck ; Retinal Dystrophies

OBJECTIVE: The CYP4V2 gene of two pedigrees affected with Bietti crystalline corneoretinal dystrophy was analyzed to indentify the cause of the disease and provide a basis for clinical diagnosis. METHODS: The probands were subjected to next generation sequencing (NGS). Suspected variants were verified by Sanger sequencing. Pathogenicity of the variants were searched through relevant databases and PubMed by following the ACMG guidelines. RESULTS: A homozygous variant in the CYP4V2 gene c. (802-8) _810delTCATACAGGTCATCGCTinsGC was detected in proband from pedigree 1, parents did not detect; CYP4V2 genes c. (802-8)_810delTCATACAGGTCATCGCTinsGC and c. 958 C>T (p.Arg320X) compound heterozygous variants existed in the proband of pedigree 2,both parents were variant carriers. The results of Sanger sequencing showed that the variant of CYP4V2 gene in the two families was consistent with the NGS sequencing. The c. (802-8)_810delTCATACAGGTCATCGCTinsGC of CYP4V2 gene was splicing variant, and both splicing variant and nonsense variant could produce truncated nonfunctional protein products. Based on standards and guidelines by American College of Medical Genetics and Genomics, the CYP4V2 genes c. (802-8)_810del TCATACAGGTCATCGCTinsGC and c. 958 C>T (p.Arg320X) were predicted to be pathogenic variants (PVS1+PS1+PM2+PM3). CONCLUSION The homozygous variant c. (802-8) _810delTCATACAGGTCATCGCTinsGC and the complex heterozygous variants c. (802-8) _810delTCATACAGGTCATCGCTinsGC and c.958C>T (p.Arg320X) in CYP4V2 gene are the cause of the disease in the probands of two pedigrees , respectively.
Corneal Dystrophies, Hereditary/pathology* ; Cytochrome P450 Family 4/genetics* ; Genetic Variation ; Humans ; Mutation ; Pedigree ; Phenotype ; Retinal Diseases/pathology*

PURPOSE: To report a rare case of Sjögren's reticular retinal dystrophy. CASE SUMMARY: A 54-year-old male presented with blurred vision and metamorphopsia in both eyes since a few years prior to his initial visit. There was a bilateral reticular network of yellow deposits throughout the posterior pole on fundus examination, which was hyperautofluorescent in fundus autofluorescence photographs. The pigment alterations were more visible with fluorescein angiography, which showed hypofluorescent lesions with hyperfluorescent borders. Spectral-domain optical coherence tomography showed elevations of the outer retina associated with the presence of subretinal hyperreflective material. Based on the conclusive correlation with clinical features, we diagnosed Sjögren's reticular retinal dystrophy. CONCLUSIONS: Sjögren's reticular retinal dystrophy is characterized by its specific pigment changes at the level of clinical manifestations and the retinal pigment epithelium. In cases of Sjögren's reticular retinal dystrophy, close monitoring is required because it has a lifetime risk of choroidal neovascularization.
Choroidal Neovascularization ; Fluorescein Angiography ; Humans ; Macular Degeneration ; Male ; Middle Aged ; Retina ; Retinal Dystrophies ; Retinal Pigment Epithelium ; Retinaldehyde ; Tomography, Optical Coherence ; Vision Disorders

OBJECTIVE: We wanted to investigate the radial peripapillary capillary (RPC) network in patients with Bietti crystalline dystrophy (BCD). METHODS: We compared RPC densities in the disk and different peripapillary regions, obtained using optical coherence tomography angiography in 22 patients with BCD (37 eyes) and 22 healthy subjects (37 eyes). The BCD group was then divided into Stage 2 and Stage 3 subgroups based on Yuzawa staging, comparing the RPC densities of the two. RESULTS: The disk area RPC density was 38.8% ± 6.3% in the BCD group and 49.2% ± 6.1% in the control group ( P < 0.001), and peripapillary region RPC density was significantly lower in the BCD group than in the control group (49.1% ± 4.7% and 54.1% ± 3.0%, respectively, P < 0.001). There were no significant RPC density differences between the tempo quadrant and inside disk of Stages 2 and 3 subgroups; the other areas showed a significantly lower RPC density in Stage 3 than in Stage 2 BCD. CONCLUSION The BCD group RPC density was significantly lower than the control group. The reduction of RPC density in the tempo quadrant occurred mainly in the Stage 1 BCD. In contrast, the reduction of RPC density in superior, inferior, and nasal quadrants occurred mainly in Stage 2.
Adult ; Aged ; Angiography ; Corneal Dystrophies, Hereditary/physiopathology* ; Female ; Humans ; Male ; Microvascular Density ; Microvessels/physiopathology* ; Middle Aged ; Retinal Diseases/physiopathology* ; Retinal Vessels/physiopathology* ; Tomography, Optical Coherence

Myotonic dystrophy is a muscular disease that is transmitted in autosomal dominant pattern. Typical features are myotonicity due to defective muscular relaxation after its contraction and muscular dystrophy. Ophthalmologic complications are cataract, retinal degeneration, hypotony, ptosis, extraocular muscle weakness, and saccadic eye movement defect. Cardiomyopathy, abnormal conduction of cardiac muscle, alopecia of frontal head, testicular atrophy, diabetes mellitus, decreased pulmonary function, and mental retardation are complications of other organs in this disease. Authors experienced two cases of cataract in two sisters with myotonic dystrophy.
Alopecia ; Atrophy ; Cardiomyopathies ; Cataract* ; Diabetes Mellitus ; Head ; Humans ; Intellectual Disability ; Muscle Weakness ; Muscular Diseases ; Muscular Dystrophies ; Myocardium ; Myotonic Dystrophy* ; Relaxation ; Retinal Degeneration ; Saccades ; Siblings*

Joubert syndrome is frequently associated with developmental delay and mental retardation, neonatal tachypnea and apnea, abnormal eye movements, and ataxia. It is inherited by an autosomal recessive trait. The most significant and constant neuropathological finding is partial or total agenesis of cerebellar vermis. Absence of the vermis results in a triangular -shaped mid-fourth ventricle and a "bat-wing"shaped fourth ventricle superiorly. The superior cerebellar peduncles are nearly horizontal. Retinal dystrophy, ocular motility disorders, and polydactyly may also occur. Symptoms may occur during the neonatal period and prognosis is grave. We report a typical case of Joubert syndrome in a 5 months-old female with developmental delay, tachypnea and intermittent apnea, abnormal eye movements, axial ataxia, and agenesis of the cerebellar vermis on brain MRI and SPECT and a brief review of related literature are also contained.
Apnea ; Ataxia ; Brain ; Eye Movements ; Female ; Fourth Ventricle ; Humans ; Infant ; Intellectual Disability ; Magnetic Resonance Imaging ; Ocular Motility Disorders ; Polydactyly ; Prognosis ; Retinal Dystrophies ; Tachypnea ; Tomography, Emission-Computed, Single-Photon

PURPOSE: To investigate the morphologic changes in the outer retina of patients with cone dystrophy, using spectral-domain optical coherence tomography (SD-OCT). METHODS: The medical records of 15 cone dystrophy patients examined from January 2007 to January 2012 were reviewed retrospectively. All patients underwent ophthalmic evaluation including best-corrected visual acuity (BCVA), color vision testing, fundus examination, full-field standard electroretinography (ERG), multifocal (mf) ERG, and SD-OCT. Qualitative and quantitative SD-OCT data and ERG responses were analyzed and compared among the patient categories and the normal control group. RESULTS: There were 4 major categories of SD-OCT findings, based on the status of the ellipsoid portion of the photoreceptor inner segment (ISe), outer segment (OS) contact cylinder, and retinal pigment epithelium (RPE) layer. Category 0 showed no structural abnormalities. Category 1 showed foveal ISe loss and obscurity of the border between the ISe band and the external limiting membrane (ELM). Category 2 showed foveal thinning and focal foveal ISe disruption with an intact ELM. Category 3 showed foveal thickening and perifoveal disruption of the ISe layer. Category 1 to 3 showed OS contact cylinder layer absence and RPE thickening. The patients in category 0 tended to be younger (mean, 10.0 years) than those in categories 1 to 3 (mean, 17.6 years), although this difference was not statistically significant. Category 1 to 3 patients exhibited statistically significant thinning of the central retina and outer nuclear layer and thickening of the RPE layer relative to the category 0 and normal control group. There was a significant correlation between the central foveal thickness and BCVA in the patients with cone dystrophy. ERG and mfERG responses did not differ significantly among the different cone dystrophy categories. CONCLUSIONS: The morphologic features of cone dystrophy as revealed by SD-OCT, could be categorized as either normal or 1 of 3 different types of outer retinal changes. The presence of normal retinal structures in young cone dystrophy patients with functional impairment (category 0) indicates that electrophysiologic studies are superior to current imaging modalities for the early diagnosis of cone dystrophy. The characteristic SD-OCT findings in cone dystrophy patients may aid in differential diagnosis and be useful for future research on the pathology of cone dystrophy.
Adolescent ; Adult ; Child ; Child, Preschool ; Electroretinography ; Female ; Fluorescein Angiography ; Fundus Oculi ; Humans ; Male ; Middle Aged ; Ophthalmoscopy ; Reproducibility of Results ; Retinal Cone Photoreceptor Cells/*pathology ; Retinal Dystrophies/*pathology/physiopathology ; Retrospective Studies ; Tomography, Optical Coherence/*methods ; Visual Acuity ; Young Adult