Neurological findings in a patient with mosaic chromosome 8 trisomy

Context: Mosaic chromosome 8 trisomy is a rare genetic disease that can develop with neurological abnormalities. Case report: A male patient had a deficit in weight gain since his first month of life, in addition to delayed speech and neuropsychomotor. At 2 years old, the family noticed that he did not see well, and then began an ophthalmological investigation that resulted in the diagnosis of bilateral congenital cataract. Moreover, it was observed that the child had microcephaly, epicanthus, and strabismus converging to the right. Abdominal ultrasound showed hepatosplenomegaly and asymmetric kidneys. Computed tomography scan of the skull was normal. Chest radiography showed an increase in cardiac volume. Bone scintigraphy revealed heterogeneous uptake of the tracer radius in the projection of the femoral diaphyses, in addition to bilateral distal femoral hypertension, with central hypoactivity being more evident on the left. Blood karyotype exhibited a mosaic chromosome 8 trisomy (mos 47, XY, + 8 [10] / 46, XY [12]). His first medullogram had been normal; however, the new test showed myelodysplasia. Conclusions: Mosaic chromosome 8 trisomy is a chromosomal abnormality characterized by quite varied clinical manifestations. Neurological changes may be present, among which are seizures. There is also a description of agenesis of the corpus callosum. In our case, speech and neuropsychomotor delay was noteworthy.

Lens-Induced Uveitis Triggered by Intravitreal Injection 40 Years after Primary Congenital Cataract Surgery with Aphakia

We report a case of a 42-year-old male with a history of bilateral congenital cataract surgery performed at 2 years of age. The patient was left with aphakia, secondary glaucoma, and a history of diabetic macular edema in the setting of diabetes mellitus type 1. The right eye became prephthisical from his congenital surgical repair, and his left eye presented with an acute pseudo-endophthalmitis developing after the seventh intravitreal injection to treat the macular edema. The eye then presented with decrease in vision, periocular injection, and a diffuse inflammatory reaction focused around the anterior residual lens capsule. The patient underwent surgical removal of the residual capsule and primary vitrectomy repair of the eye, achieving a significant improvement in visual symptoms and recovery of visual and anatomic function.

Pseudodominant Nanophthalmos in a Roma Family Caused by a Novel PRSS56 Variant

Background. The aim of the study was to identify the molecular genetic cause of two different Mendelian traits with ocular involvement present in the members of a single consanguineous Czech Roma family. Methods. We have performed ocular examination and review of medical records in two individuals diagnosed with nanophthalmos (proband and her father) and one individual followed for bilateral congenital cataract and microcornea (uncle of the proband). DNA of subjects with nanophthalmos was analysed by exome sequencing. Sanger sequencing was applied for targeted screening of potentially pathogenic variants and to follow segregation of identified variants within the family. Results. A homozygous variant c.1509G>C; p.(Met503Ile), in PRSS56 was found in the two individuals affected with nanophthalmos. The change was absent from the gnomAD dataset, but two out of 118 control Roma individuals were also shown to be heterozygous carriers. Analysis of single nucleotide polymorphisms in linkage disequilibrium with the c.1509G>C in PRSS56 suggested a shared chromosomal segment. The nanophthalmos phenotype, characterized in detail in the younger individual, encompassed bilateral corneal steepening, retinal folds, buried optic head drusen, and restricted visual fields, but no signs of retinal dystrophy. A known pathogenic founder CTDP1 variant c.863+389C>T in a homozygous state was identified in the other family member confirming the suspected diagnosis of congenital cataracts, facial dysmorphism, and demyelinating neuropathy syndrome. Conclusions. Herein, we report the first occurrence of nanophthalmos in the Roma population. We have identified pseudodominant inheritance for this phenotype caused by a novel variant in PRSS56, representing a possible founder effect. Despite advances in genetic technologies such as exome sequencing, careful phenotype evaluation in patients from an isolated population, along with an awareness of population-specific founder effects, is necessary to ensure that accurate molecular diagnoses are made.

Molecular Etiology of Isolated Congenital Cataract Using Next-Generation Sequencing: Single Center Exome Sequencing Data from Turkey

Congenital cataract, which refers to lenticular opacity diagnosed at birth or more commonly during the first year of life, is one of the leading causes of childhood blindness. Molecular understanding of the disease pathogenesis has evolved thanks to many studies based on modern technologies. In this study, we aimed to identify and discuss the molecular etiology of nonsyndromic or nonmetabolic bilateral congenital cataract by whole-exome sequencing (WES). Patients with bilateral congenital cataract presumed to be isolated after metabolic and genetic evaluation were enrolled in the study. All patients underwent detailed ophthalmological examination and bilateral cataract surgery. DNA samples of the probands, parents, and available affected family members were analyzed by WES. Variants were validated and confirmed by Sanger sequencing in all probands and in available affected family members. A total of 4 patients (3 girls and 1 boy) were recruited. Two patients had nuclear, 1 patient had total, and 1 patient had combined lamellar and sutural cataract. One family had consanguinity. A heterozygous c.215+1G&#x3e;A mutation in <i>CRYBA1</i>, heterozygous c.432C&#x3e;G (p.Tyr144Ter) mutation in <i>CRYGC</i>, heterozygous c.70A&#x3e;C (p.Pro24Thr) mutation in <i>CRYGD</i>, and a heterozygous c.466G&#x3e;A (p.Gly156Arg) mutation in <i>CRYBB3</i> were detected. All these mutations were confirmed by Sanger sequencing in selected affected individuals. The current study identified all causative mutations of congenital cataract in the crystalline genes. The results confirmed that WES is a very useful tool in the investigation of the diseases with heterogeneous genetic background.