Fuchs' Adenoma of the Choroid Simulating a Choroidal Hemangioma

We report the case of a 54-year-old female who was referred to us with an amelanotic mass on the posterior pole of the left eye involving the macula. Fundus fluorescein angiography revealed a hyperfluorescent choroidal mass. Indocyanine green chorioangiography revealed a hypofluorescent choroidal lesion with hyperfluorescent margins. B-scan ultrasonography showed a choroidal mass with moderate reflectivity. Choroidal biopsy was performed, which revealed the diagnosis of Fuchs' adenoma

Off-resonance saturation as an MRI method to quantify mineral- iron in the post-mortem brain

PURPOSE: To employ an off‐resonance saturation method to measure the mineral‐iron pool in the postmortem brain, which is an endogenous contrast agent that can give information on cellular iron status. METHODS: An off‐resonance saturation acquisition protocol was implemented on a 7 Tesla preclinical scanner, and the contrast maps were fitted to an established analytical model. The method was validated by correlation and Bland‐Altman analysis on a ferritin‐containing phantom. Mineral‐iron maps were obtained from postmortem tissue of patients with neurological diseases characterized by brain iron accumulation, that is, Alzheimer disease, Huntington disease, and aceruloplasminemia, and validated with histology. Transverse relaxation rate and magnetic susceptibility values were used for comparison. RESULTS: In postmortem tissue, the mineral‐iron contrast colocalizes with histological iron staining in all the cases. Iron concentrations obtained via the off‐resonance saturation method are in agreement with literature. CONCLUSIONS: Off‐resonance saturation is an effective way to detect iron in gray matter structures and partially mitigate for the presence of myelin. If a reference region with little iron is available in the tissue, the method can produce quantitative iron maps. This method is applicable in the study of diseases characterized by brain iron accumulation and can complement existing iron‐sensitive parametric methods

Aqueous Humor Biomarkers Identify Three Prognostic Groups in Uveal Melanoma

Purpose: To investigate whether we can identify different patterns of inflammation in the aqueous humor of a uveal melanoma (UM)-containing eye, and whether these are related to prognosis. Meth

Biallelic loss of LDB3 leads to a lethal pediatric dilated cardiomyopathy

Autosomal dominant variants in LDB3 (also known as ZASP), encoding the PDZ-LIM domain-binding factor, have been linked to a late onset phenotype of cardiomyopathy and myofibrillar myopathy in humans. However, despite knockout mice displaying a much more severe phenotype with premature death, bi-allelic variants in LDB3 have not yet been reported. Here we identify biallelic loss-of-function variants in five unrelated cardiomyopathy families by next-generation sequencing. In the first family, we identified compound heterozygous LOF variants in LDB3 in a fetus with bilateral talipes and mild left cardiac ventricular enlargement. Ultra-structural examination revealed highly irregular Z-disc formation, and RNA analysis demonstrated little/no expression of LDB3 protein with a functional C-terminal LIM domain in muscle tissue from the affected fetus. In a second family, a homozygous LDB3 nonsense variant was identified in a young girl with severe early-onset dilated cardiomyopathy with left ventricular non-compaction; the same homozygous nonsense variant was identified in a third unrelated female infant with dilated cardiomyopathy. We further identified homozygous LDB3 frameshift variants in two unrelated probands diagnosed with cardiomegaly and severely reduced left ventricular ejection fraction. Our findings demonstrate that recessive LDB3 variants can lead to an early-onset severe human phenotype of cardiomyopathy and myopathy, reminiscent of the knockout mouse phenotype, and supporting a loss of function mechanism

Bi-allelic <i>NIT1 </i>variants cause a brain small vessel disease characterized by movement disorders, massively dilated perivascular spaces, and intracerebral hemorrhage

Purpose: To describe a recessively inherited cerebral small vessel disease, caused by loss-of-function variants in Nitrilase1 (NIT1). Methods:We performed exome sequencing, brain magnetic resonance imaging, neuropathology, electron microscopy, western blotting, and transcriptomic and metabolic analyses in 7 NIT1-small vessel disease patients from 5 unrelated pedigrees. Results: The first identified patients were 3 siblings, compound heterozygous for the NIT1 c.727C&gt;T; (p.Arg243Trp) variant and the NIT1 c.198_199del; p.(Ala68∗) variant. The 4 additional patients were single cases from 4 unrelated pedigrees and were all homozygous for the NIT1 c.727C&gt;T; p.(Arg243Trp) variant. Patients presented in mid-adulthood with movement disorders. All patients had striking abnormalities on brain magnetic resonance imaging, with numerous and massively dilated basal ganglia perivascular spaces. Three patients had non-lobar intracerebral hemorrhage between age 45 and 60, which was fatal in 2 cases. Western blotting on patient fibroblasts showed absence of NIT1 protein, and metabolic analysis in urine confirmed loss of NIT1 enzymatic function. Brain autopsy revealed large electron-dense deposits in the vessel walls of small and medium sized cerebral arteries. Conclusion: NIT1-small vessel disease is a novel, autosomal recessively inherited cerebral small vessel disease characterized by a triad of movement disorders, massively dilated basal ganglia perivascular spaces, and intracerebral hemorrhage.</p

Bi-allelic <i>NIT1 </i>variants cause a brain small vessel disease characterized by movement disorders, massively dilated perivascular spaces, and intracerebral hemorrhage

Purpose: To describe a recessively inherited cerebral small vessel disease, caused by loss-of-function variants in Nitrilase1 (NIT1). Methods:We performed exome sequencing, brain magnetic resonance imaging, neuropathology, electron microscopy, western blotting, and transcriptomic and metabolic analyses in 7 NIT1-small vessel disease patients from 5 unrelated pedigrees. Results: The first identified patients were 3 siblings, compound heterozygous for the NIT1 c.727C&gt;T; (p.Arg243Trp) variant and the NIT1 c.198_199del; p.(Ala68∗) variant. The 4 additional patients were single cases from 4 unrelated pedigrees and were all homozygous for the NIT1 c.727C&gt;T; p.(Arg243Trp) variant. Patients presented in mid-adulthood with movement disorders. All patients had striking abnormalities on brain magnetic resonance imaging, with numerous and massively dilated basal ganglia perivascular spaces. Three patients had non-lobar intracerebral hemorrhage between age 45 and 60, which was fatal in 2 cases. Western blotting on patient fibroblasts showed absence of NIT1 protein, and metabolic analysis in urine confirmed loss of NIT1 enzymatic function. Brain autopsy revealed large electron-dense deposits in the vessel walls of small and medium sized cerebral arteries. Conclusion: NIT1-small vessel disease is a novel, autosomal recessively inherited cerebral small vessel disease characterized by a triad of movement disorders, massively dilated basal ganglia perivascular spaces, and intracerebral hemorrhage.</p

Soluble HLA in the aqueous humour of uveal melanoma is associated with unfavourable tumour characteristics

A high HLA expression in uveal melanoma (UM) is part of the prognostically unfavorable inflammatory phenotype. We wondered whether the presence of soluble HLA (sHLA) in the aqueous humour is associated with clinical, histopathological or genetic tumour characteristics, and represents tumour HLA expression and intratumoural inflammation. Aqueous humour from 108 UM patients was analysed for the presence of sHLA, using a Luminex assay specific for HLA Class I. Clinical and genetic parameters were compared between sHLA-positive and negative eyes. A qPCR analysis was performed on tumour tissue using a Fluidigm assay. In 19/108 UM-containing eyes, the sHLA level in the aqueous was above the detection limit. Tumours in sHLA-positive eyes were significantly larger, more frequently involved the ciliary body, and more often showed monosomy 3, gain of chromosome 8q and loss of BAP1 staining. Melanoma-related survival was worse in patients with sHLA-positive aqueous humour. sHLA in the aqueous did not represent the tumour's HLA expression and did not relate to immune cell infiltration in the tumour. We conclude that UM-containing eyes may contain sHLA in the aqueous humour, where it is a prognostically-unfavourable sign and may influence local immune responses