Macular corneal dystrophy with iridofundal coloboma in the same patient: a unique combination.

A young a presented with painless, progressive diminution of vision in both eyes (BE). Slit lamp examination revealed the presence of a single central corneal opacity in the right eye and multiple corneal opacities of varying sizes in the left eye (LE), limited to the anterior-mid corneal stroma. Microcornea with reduced central corneal thickness and complete inferonasal iris coloboma along with inferior fundal coloboma, sparing both the disc and macula, were noted in BE. A diagnosis of BE macular corneal dystrophy (MCD) and iridofundal coloboma (IFC) was made. The patient underwent LE sutureless anterior lamellar therapeutic keratoplasty. On histopathological examination, the excised corneal tissue revealed stromal lamellar disarray with positive colloidal iron staining, strongly suggestive of MCD. Whole-exome sequencing revealed the presence of a likely pathogenic carbohydrate sulfotransferase 6 (CHST6) mutation, confirming the diagnosis of MCD. This concurrent presence of IFC with a corneal stromal dystrophy is previously unreported in the literature, to the best of our knowledge.

Bilateral Peters' anomaly, aniridia and Wilms tumour (WAGR syndrome) in monozygotic twins.

AIM: This study reports the bilateral association of Peters' anomaly and congenital aniridia in monozygotic twins subsequently diagnosed with Wilms tumour (WAGR syndrome). METHODS: Two monozygotic female twins were referred at age 2 months with bilateral corneal opacity. A diagnosis of Peters' anomaly associated to aniridia was made in both eyes of both twins. Physical examination and ultrasonography were carried out at 12 months of age to explore the possibility of WAGR-related anomalies, specifically Wilms tumour. DNA were isolated and subjected to whole exome sequencing. RESULTS: Peters' anomaly associated to aniridia in both eyes as well as bilateral Wilms tumour in both children were diagnosed. Exome analyses showed a large heterozygous deletion encompassing 6 648 473 bp in chromosome 11p13, using Integrative Genomics Viewer and AnnotSV software. CONCLUSION: WAGR syndrome is a rare contiguous gene deletion syndrome with a greater risk of developing Wilms tumour associated with Peters' anomaly and congenital aniridia. However, co-occurrence of both anomalies was rarely reported in twins, and never in both eyes of monozygotic twins. Here, we report the bilateral association of Peters' anomaly and congenital aniridia in monozygotic twins with WAGR syndrome.

Variable Phenotype of Congenital Corneal Opacities in Biallelic CYP1B1 Pathogenic Variants.

PURPOSE: The aim of this study is to describe the variable phenotype of congenital corneal opacities occurring in patients with biallelic CYP1B1 pathogenic variants. METHODS: A retrospective chart review was conducted to identify patients with congenital corneal opacities and CYP1B1 pathogenic variants seen at UPMC Children's Hospital of Pittsburgh. Ophthalmic examination, high-frequency ultrasound, anterior segment optical coherence tomography, histopathologic images, and details of genetic testing were reviewed. RESULTS: Three children were identified. All presented with raised intraocular pressure. Two patients showed bilateral limbus-to-limbus avascular corneal opacification that did not resolve with intraocular pressure control; 1 showed unilateral avascular corneal opacity with a crescent of clear cornea, iridocorneal adhesions, iridolenticular adhesions, and classical features of congenital glaucoma in the fellow eye (enlarged corneal diameter, Haab striae, and clearing of the corneal clouding with appropriate intraocular pressure control). The first 2 patients were visually rehabilitated with penetrating keratoplasty. Histopathology revealed distinct features: a variably keratinized epithelium; a thick but discontinuous Bowman-like layer with areas of disruption and abnormal cellularity; Descemet membrane, when observed, showed reduced endothelial cells; and no pathological changes of Haab striae were identified. Two patients had compound heterozygous pathogenic variants in CYP1B1 causing premature stop codons, whereas 1 was homozygous for a pathogenic missense variant. CONCLUSIONS: Congenital corneal opacities seen in biallelic CYP1B1 pathogenic variants have a variable phenotype. One is that commonly termed as Peters anomaly type 1 (with iridocorneal adhesions, with or without iridolenticular adhesions) and the other is a limbus-to-limbus opacity, termed CYP1B1 cytopathy. Clinicians should be aware of this phenotypic variability.

Magnetic Resonance Imaging Findings and Genetic Testing Results in Children With Congenital Corneal Opacities.

PURPOSE: This study investigates brain and globe abnormalities identified on magnetic resonance imaging (MRI) in children with congenital corneal opacities (CCO). DESIGN: Retrospective cohort study. METHODS: Clinical notes, radiology records, and genetic testing results were reviewed for patients diagnosed with corneal opacification within the first 6 months of life at a tertiary referral academic center between August 2008 and January 2018. Ocular findings, systemic anomalies, neuroimaging, and genetic testing results were summarized. RESULTS: A total of 135 patients presenting at age 1 day to 12 years (mean age, 1 year) were identified. Children with bilateral CCO were more likely to have systemic disease (P = 0.018). Of the entire cohort, 43 (31.8%) patients received MRI, of whom 27 (62.8%) had abnormal brain findings and 30 (69.7%) had abnormal orbital findings. The most common abnormal brain findings were ventriculomegaly (n = 16, 59.2%) and corpus callosum abnormalities (n = 10, 37.0%) followed by brainstem/pons anomalies (n = 5, 18.5%), and cerebellar anomalies (n = 2, 7.4%). Abnormal brain MRI findings were associated with the presence of neurologic (P = .003) and craniofacial (P = .034) disease. A total of 44 (32.1%) patients underwent genetic testing, of whom 29 (65.9%) had pathogenic results. CONCLUSIONS: More than 60% of the children with CCO who underwent MRI had abnormal brain and orbit findings that were correlated with significant neurologic disease. Furthermore, almost two-thirds of patients with CCO who underwent genetic testing had pathogenic results. These data demonstrate the value of systemic workup in children with CCO, and highlight the role of ophthalmologists in facilitating the diagnosis of systemic comorbidities associated with CCO.

Ocular Manifestations of Peters Plus-Like Syndrome in 8q21.11 Microdeletion Syndrome.

PURPOSE: The aim of this study was to report a case of Peters plus-like syndrome, which revealed to have an 8q21.11 microdeletion by copy number variation analysis using exome data. METHODS: A 6-month-old Japanese boy presented with bilateral corneal opacity since birth. The right eye maintained central corneal transparency with slightly inferior nasal and superior peripheral corneal opacities. The entire cornea was opacified in the left eye, particularly in the superior quadrants with vascularization, suggesting Peters anomaly. Identification of intraocular structures in the left eye was difficult; however, hypoplasia of the circumferential anterior iris stroma appeared bilaterally present, and no abnormalities were present in the posterior segment on funduscopic examination of the right eye and ultrasonography in the left eye. He had several facial malformations in addition to corneal opacity, but no other external abnormalities. General examination, including biochemical tests of blood and urine, physiological and imaging tests including abdominal echo, auditory brain stem response, brain computed tomography, and magnetic resonance imaging, showed no abnormalities. However, the patient showed intellectual disability and delayed motor development. RESULTS: Although his karyotype was normal, copy number variation analysis using exome data and subsequent quantitative polymerase chain reaction identified a de novo 4.6-Mb deletion at 8q21.11q21.13; thus, the patient was diagnosed with 8q21.11 microdeletion syndrome. CONCLUSIONS: We identified a de novo 4.6-Mb deletion at 8q21.11q21.13 in a patient with ophthalmic anterior segment dysgenesis and systemic complications, clinically diagnosed as Peters plus-like syndrome. Clinically, the 8q21.11 microdeletion syndrome shows a phenotype similar to that of Peters plus syndrome, and a genetic diagnosis is required.

Variable phenotype of secondary congenital corneal opacities associated with microphthalmia with linear skin defects syndrome.

To describe the anterior segment (AS) findings in patients with microphthalmia with linear skin defects syndrome (MLS), also known as microphthalmia, dermal aplasia, and sclerocornea (MIDAS). A retrospective chart review was conducted to identify patients with a diagnosis of MLS syndrome seen at UPMC Children's Hospital of Pittsburgh. Ophthalmic examination, high-frequency ultrasound, AS optical coherence tomography, and molecular testing were reviewed. Five female patients (10 eyes) were identified. One eye was anophthalmic, one was in a status post penetrating keratoplasty, and eight eyes presented with congenital corneal opacity (CCO). Of these, one showed a normal lens and a very small faint CCO; five showed congenital aphakia and characteristic silvery appearance of the cornea with vascularization; and two showed irido-corneal adhesions in association with normal or abnormal lens and localized avascular CCO. Genetic testing was performed and revealed involvement of HCCS in four patients. In MLS patients, kerato-irido-lenticular dysgenesis can be associated with secondary CCO. It is important to distinguish these CCO from sclerocornea, in order to refine the appropriate management and counseling the parents about the prognosis.

Congenital Corneal Opacity in 22q11.2 Deletion Syndrome: A Case Series.

PURPOSE: The purpose of this study was to describe the deep phenotype of congenital corneal opacities (CCO) in patients with 22q11.2 deletion syndrome (22q11.2 DS) and to identify putative regions or genes that could explain the CCO. METHODS: A retrospective chart review was conducted to identify patients with 22q11.2 DS seen in the ophthalmology clinic of a tertiary referral children's hospital. Thirty patients were identified, with molecular confirmation. Twenty-six did not show structural anterior segment anomalies aside from posterior embryotoxon (n = 4), whereas 4 had bilateral CCO, of which 3 had preoperative images. We reviewed medical, operative, and pathology reports; anterior segment optical coherence tomography; high-frequency ultrasound; histopathologic slides; and genetic testing. To identify putative genes responsible for CCO, chromosomal breakpoints in patients with and without CCO were compared. RESULTS: In the 3 patients with preoperative imaging and CCO, a pattern of paracentral corneal opacification with central clearing accompanied by iridocorneal or keratolenticular adhesions was observed. Anterior segment optical coherence tomography and histopathologic images showed central stromal thinning with a residual structure consistent with Descemet membrane. One patient presented at birth with unilateral corneal perforation, suggestive of likely stromal thinning. A comparison of the breakpoints across all cases failed to reveal unique regions or genes in patients with CCO. CONCLUSIONS: 22q11.2 DS can rarely be associated with CCO. We describe a consistent pattern of central clearing related to posterior stromal thinning, with or without ICA/KLA. Possible candidate genes for corneal opacification in 22q11.2 DS remain elusive.

A Case of Clinically Atypical Gelatinous Drop-like Corneal Dystrophy With Unilateral Recurrent Amyloid Depositions.

PURPOSE: The purpose of this article was to describe the successful diagnosis and management of clinically atypical, unilateral, gelatinous drop-like corneal dystrophy (GDLD) in a pediatric patient. METHODS: This study was a case report. RESULTS: A 7-year-old Japanese girl was referred to our clinic with right corneal opacity for over 3 years. Slitlamp examination revealed a white, protruding, paracentral corneal opacity with an irregular surface and tiny stromal lattice figures with subepithelial opacities. No trichiasis or epiblepharon was observed, and the patient's right corrected distance visual acuity (CDVA) was 18/20. The contralateral cornea was intact but demonstrated fluorescein uptake. After 8 months, the right CDVA worsened from 18/20 to 6/20, and corneal epithelial scraping was performed. Histopathological analysis revealed amyloid nodules in the subepithelial layer and in the anterior corneal stroma stained with Congo red, which reoccurred 2 months after the procedure, and corneal dystrophy was suspected. Isolation and sequencing of the genomic DNA revealed a homozygous p.Gln118Ter. mutation in TACSTD2 in the patient and heterozygous p.Gln118Ter. mutations in both parents. GDLD was diagnosed; bilateral use of therapeutic soft contact lenses was prescribed after the first corneal scraping. No additional surgical intervention was required for the right eye for 4.5 years. CDVA of the contralateral left eye has been successfully maintained at 30/20 over this period, without emergence of nodular lesions or corneal opacities. CONCLUSIONS: We encountered a patient with early, atypical GDLD, who was definitively diagnosed using genomic DNA sequencing. GDLD should be a part of the differential diagnosis in patients presenting with unilateral, recurrent amyloid deposition.

Congenital corneal opacities as a new feature in an unusual case of White-Sutton syndrome.

A 2-week-old girl presented with bilateral congenital corneal opacities. Additional systemic manifestations included microcephaly, patent foramen ovale, and poor feeding. Patient and parents underwent whole exome sequencing trio analysis that revealed a de novo pathogenic variant in POGZ (p.Val1150GlyfsX8), which is causative of the White-Sutton syndrome. This rare genetic condition is usually associated with intellectual and developmental delay, facial dysmorphism, strabismus, refractive error, and retinal changes. To our knowledge, this is the first reported case of White-Sutton syndrome presenting with congenital corneal opacities.

A novel homozygous frameshift mutation in the APOA1 gene associated with marked high-density lipoprotein deficiency.

The proband was a 53-year-old Japanese woman. Despite having no atherosclerotic vascular lesions on a physiological examination, markedly decreased levels of high-density lipoprotein (HDL) were always noted at her annual medical checkup. She also had corneal opacities but neither xanthoma nor tonsillar hypertrophy. A biochemical examination showed decreased levels of both apolipoprotein A-I (apoA-I) (<5 mg/dL) and lecithin-cholesterol acyltransferase (LCAT) activity. Her brother and son also had low concentrations of HDL-cholesterol, suggesting the presence of a genetic abnormality. Therefore, a sequence analysis of the genes for ABCA1, LCAT and apoA-I proteins was performed in the proband. The analysis of the APOA1 gene revealed a novel homozygous two-nucleotide deletion in exon 4 (c.614_615delTC), which causes a frameshift after residue 205 of the apoA-I protein (p.Leu205fs). Since no mutation has been found in the ABCA1 or LCAT gene, functional abnormalities of the carboxyl-terminal region of the apoA-I protein in lipid binding might have caused the low HDL-cholesterol levels and decreased LCAT activity, possibly associated with corneal opacities but not premature CAD, in the patient.

[Diagnostics, clinical aspects and genetics of congenital corneal opacities]. / Diagnostik, Klinik und Genetik kongenitaler Hornhauttrübungen.

BACKGROUND: Congenital corneal opacities are comparatively rare diseases with high amblyogenic potential. PURPOSE: The present work provides an overview of the diagnostics, clinical aspects and genetics of congenital corneal opacities. METHODS: A literature search was carried out to compile an overview and illustration with own clinical case examples. RESULTS: Differentiated diagnostics are of high importance in the treatment of patients with congenital corneal opacities. A close cooperation between the medical departments involved and also the parents is absolutely essential. The structured classification of congenital corneal opacities provides the basis for a targeted treatment. DISCUSSION: The causes and the clinical symptoms of congenital corneal opacities are manifold. The correct diagnosis should be made early and in an interdisciplinary manner. Based on this, conservative and surgical treatment measures can be planned and an impending development of amblyopia can be specifically counteracted.

First evidence of SOX2 mutations in Peters' anomaly: Lessons from molecular screening of 95 patients.

Peters' anomaly (PA) is a rare anterior segment dysgenesis characterized by central corneal opacity and irido-lenticulo-corneal adhesions. Several genes are involved in syndromic or isolated PA (B3GLCT, PAX6, PITX3, FOXE3, CYP1B1). Some copy number variations (CNVs) have also been occasionally reported. Despite this genetic heterogeneity, most of patients remain without genetic diagnosis. We retrieved a cohort of 95 individuals with PA and performed genotyping using a combination of comparative genomic hybridization, whole genome, exome and targeted sequencing of 119 genes associated with ocular development anomalies. Causative genetic defects involving 12 genes and CNVs were identified for 1/3 of patients. Unsurprisingly, B3GLCT and PAX6 were the most frequently implicated genes, respectively in syndromic and isolated PA. Unexpectedly, the third gene involved in our cohort was SOX2, the major gene of micro-anophthalmia. Four unrelated patients with PA (isolated or with microphthalmia) were carrying pathogenic variants in this gene that was never associated with PA before. Here we described the largest cohort of PA patients ever reported. The genetic bases of PA are still to be explored as genetic diagnosis was unavailable for 2/3 of patients. Nevertheless, we showed here for the first time the involvement of SOX2 in PA, offering new evidence for its role in corneal transparency and anterior segment development.

Suppression of lipopolysaccharide-induced corneal opacity by hepatocyte growth factor.

Keratitis induced by bacterial toxins, including lipopolysaccharide (LPS), is a major cause of corneal opacity and vision loss. Our previous study demonstrates hepatocyte growth factor (HGF) promotes epithelial wound healing following mechanical corneal injury. Here, we investigated whether HGF has the capacity to suppress infectious inflammatory corneal opacity using a new model of LPS-induced keratitis. Keratitis, induced by two intrastromal injections of LPS on day 1 and 4 in C57BL/6 mice, resulted in significant corneal opacity for up to day 10. Following keratitis induction, corneas were topically treated with 0.1% HGF or PBS thrice daily for 5 days. HGF-treated mice showed a significantly smaller area of corneal opacity compared to PBS-treated mice, thus improving corneal transparency. Moreover, HGF treatment resulted in suppression of α-SMA expression, compared to PBS treatment. HGF-treated corneas showed normalized corneal structure and reduced expression of pro-inflammatory cytokine, demonstrating that HGF restores corneal architecture and immune quiescence in corneas with LPS-induced keratitis. These findings offer novel insight into the potential application of HGF-based therapies for the prevention and treatment of infection-induced corneal opacity.

A novel pathogenic variant in LCAT causing FLD. A case report.

BACKGROUND: Fish-eye disease (FED) is due to a partial deficiency in LCAT activity. Nevertheless, Familial lecithin-cholesterol acyltransferase deficiency (FLD), also called Norum disease, appears when the deficiency is complete. They are both rare genetic disorders inherited in an autosomal recessive manner. Clinical signs include decreased circulating HDL cholesterol and dense corneal opacity. Kidney injuries also affect patients suffering from FLD. The diagnosis of FLD is based on the presence of characteristic signs and symptoms and confirmed by genetic testing. CASE PRESENTATION: We present a case of a 63-year-old man showing an altered lipid profile with low HDL cholesterol, chronic kidney disease (CKD) and corneal disorders. He was referred to genetic counseling in order to discard genetic LCAT deficiency due to decreased visual acuity caused by corneal opacity. A massive DNA sequencing was conducted using a multigene panel associated with lipid metabolism disturbances. RESULTS AND GENETIC FINDINGS: Two likely pathogenic variants in LCAT were identified and later confirmed by Sanger sequencing. Both (c.491 G > A and c.496 G > A) were missense variants that originated an amino acid substitution (164Arginine for Histidine and 166Alanine for Threonine, respectively) modifying the protein sequence and its 3D structure. CONCLUSIONS: FLD and FED sharing common biochemical features, and the existence of other diseases with similar clinical profiles underline the need for a timely differential diagnosis aiming to address patients to preventive programs and future available therapies. This case, added to the reduced number of publications previously reported regarding FLD and FED, contributes to better understanding the genetic characteristics, clinical features, and diagnosis of these syndromes.

Comprehensive phenotypic and functional analysis of dominant and recessive FOXE3 alleles in ocular developmental disorders.

The forkhead transcription factor FOXE3 is critical for vertebrate eye development. Recessive and dominant variants cause human ocular disease but the full range of phenotypes and mechanisms of action for the two classes of variants are unknown. We identified FOXE3 variants in individuals with congenital eye malformations and carried out in vitro functional analysis on selected alleles. Sixteen new recessive and dominant families, including six novel variants, were identified. Analysis of new and previously reported genetic and clinical data demonstrated a broad phenotypic range with an overlap between recessive and dominant disease. Most families with recessive alleles, composed of truncating and forkhead-domain missense variants, had severe corneal opacity (90%; sclerocornea in 47%), aphakia (83%) and microphthalmia (80%), but some had milder features including isolated cataract. The phenotype was most variable for recessive missense variants, suggesting that the functional consequences may be highly dependent on the type of amino acid substitution and its position. When assessed, aniridia or iris hypoplasia were noted in 89% and optic nerve anomalies in 60% of recessive cases, indicating that these defects are also common and may be underrecognized. In dominant pedigrees, caused by extension variants, normal eye size (96%), cataracts (99%) and variable anterior segment anomalies were seen in most, but some individuals had microphthalmia, aphakia or sclerocornea, more typical of recessive disease. Functional studies identified variable effects on the protein stability, DNA binding, nuclear localization and transcriptional activity for recessive FOXE3 variants, whereas dominant alleles showed severe impairment in all areas and dominant-negative characteristics.

Peters Anomaly in Nail-Patella Syndrome: A Case Report and Clinico-Genetic Correlation.

PURPOSE: The purpose of this study was to report the clinicopathological features of Peters anomaly in a child with nail-patella syndrome. METHODS: Nail-patella syndrome (NPS) is a rare autosomal dominant connective tissue disorder characterized by several anomalies of the extremities, joints and nails, glomerulopathy, and rarely ocular involvement. NPS is caused by heterozygous loss-of-functional mutations in the LMX1B gene that encodes the LIM homeodomain proteins. RESULTS: This case reports a new association of Peters anomaly in a child with NPS that also had classic skeletal/nail anomalies and protein losing nephropathy. Furthermore, DNA sequence analysis identified a novel missense heterozygous mutation in the LMX1B gene (Transcript ID: NM_001174146) resulting in the replacement of tryptophan by serine in codon 266, suggesting that the mutation (p.Trp.266Ser) affects LMX1B function by disturbing its interactions with other proteins. To the best of our knowledge, this association of Peters anomaly is novel and has not been reported earlier in the ophthalmic and systemic literature on NPS. CONCLUSION: The corneal findings in our case with NPS are similar to those seen in congenital corneal opacification because of Peters anomaly. This novel association of Peters anomaly with NPS may be related to the effects of the LMX1B mutation on corneal development.

Dominant variants in PRR12 result in unilateral or bilateral complex microphthalmia.

Complex microphthalmia is characterized by small eyes with additional abnormalities that may include anterior segment dysgenesis. While many genes are known, a genetic cause is identified in only 4-30% of microphthalmia, with the lowest rate in unilateral cases. We identified four novel pathogenic loss-of-function alleles in PRR12 in families affected by complex microphthalmia and/or Peters anomaly, including two de novo, the first dominantly transmitted allele, as well as the first splicing variant. The ocular phenotypes were isolated with no additional systemic features observed in two unrelated families. Remarkably, ocular phenotypes were asymmetric in all individuals and unilateral (with structurally normal contralateral eye) in three. There are only three previously reported PRR12 variants identified in probands with intellectual disability, neuropsychiatric disorders, and iris anomalies. While some overlap with previously reported cases is seen, nonsyndromic developmental ocular anomalies are a novel phenotype for this gene. Additional phenotypic expansions included short stature and normal development/cognition, each noted in two individuals in this cohort, as well as absence of neuropsychiatric disorders in all. This study identifies new associations for PRR12 disruption in humans and presents a genetic diagnosis resulting in unilateral ocular phenotypes in a significant proportion of cases.

Bilateral severe microphthalmia in a neonate with trisomy 8 mosaicism: A new finding.

Mosaic Trisomy 8 is a rare chromosomal abnormality estimated to occur one in 30,000 newborns. The phenotype is highly variable and the severity does not appear to be correlated with the proportion of cells that contain the additional chromosome. Ocular involvement in Trisomy 8 mosaicism has previously been described to include corneal opacities, retinal dystrophy, coloboma, and unilateral microphthalmia. We report a case of severe bilateral microphthalmia in a neonate with Trisomy 8 mosaicism, a previously unrecognized ophthalmic manifestation.

Identification of a New Genetic Mutation Associated With Peters Anomaly.

PURPOSE: To report a new genetic mutation in the COL4A1 gene, which was identified in a baby girl with Peters anomaly (PA), a rare anterior segment mesenchymal dysgenesis, which is characterized by unilateral or bilateral corneal opacities often accompanied by glaucoma, cataract, and systemic malformations and associated with various genetic mutations. METHODS: Ophthalmologic examination of one baby girl and whole exome sequencing and Sanger sequencing of blood samples of the child and her biological parents were performed. RESULTS: Ophthalmologic examination led to the diagnosis of PA type I in the baby girl. Whole exome sequencing and Sanger sequencing identified the de novo mutation c.181_189delinsAGGTTTCCG; p.Gly61Arg in the COL4A1 gene in the child, whereas no other putatively causative variants in established genes associated with anterior segment dysgenesis were present. CONCLUSIONS: PA might be associated with the mutation c.181_189delinsAGGTTTCCG; p.Gly61Arg in the COL4A1 gene. The COL4A1 gene encodes for collagen IVα1, an essential component of basal membranes, and mutations are associated with an increased risk for renal and cerebrovascular disorders and stroke. This should be considered when advising and monitoring patients.

A mutation in DOP1B identified as a probable cause for autosomal recessive Peters anomaly in a consanguineous family.

Purpose: Peters anomaly (PA) is a heterogeneous developmental disorder characterized by central corneal opacity and iridocorneal or corneolenticular adhesions. Although many causative genes have been identified, most screened patients do not have mutations in the known genes. We aimed to identify the genetic cause of Peters anomaly in a pedigree with three affected individuals. Methods: Slit-lamp biomicroscopy and ultrasound biomicroscopy were performed for definitive diagnosis. Exome sequencing was conducted on the DNA of all three patients. After identification of a candidate causative gene, expression of the gene was assessed with real-time PCR in various ocular tissues of three human embryos and three adults. Results: The patients were affected with isolated PA. The parents of the patients were related to one another. Inheritance of PA was autosomal recessive. After appropriate filtering of the exome data, a homozygous variation in DOP1B remained as the only candidate genetic cause of PA in the pedigree. The variant segregated with disease status in the pedigree and was absent among 800 control Iranians. The variant has been reported in various databases at frequencies of 0.006 or less only in the heterozygous state in some cohorts of African origin. The p.Val1660 amino acid affected by the mutation is completely conserved in mammals and birds during evolution. Expression of DOP1B was shown in all adult and embryonic lens, iris, cornea, sclera, and retina tissues that were tested. Conclusions: DOP1B that encodes DOP1 leucine zipper like protein B was identified as the putative PA-causing gene in pedigree PA-101. As DOP1B is positioned within the Down syndrome chromosomal region on chromosome 21, until now this gene has mostly been studied with respect to brain functions. However, members of the Dopey gene family have been shown to have roles in development in other organisms. Evidence of the expression of DOP1B in various PA-relevant eye tissues, which, to the best of our knowledge, is shown here for the first time, is to be noted. However, this finding does not necessarily implicate a specific role for DOP1B in eye development as the gene is expressed in many tissues. Ultimately, definitive assessment of the contribution of DOP1B to PA pathology awaits identification of mutations in the gene in unrelated patients with PA and functional studies.