Dataset Information

Congenital toxoplasmosis as one phenocopy of North Carolina Macular Dystrophy (NCMD/MCDR1).

ABSTRACT:

Purpose

To highlight the striking similarities between the lesions of congenital toxoplasmosis (CT) and North Carolina Macular Dystrophy (NCMD) using multimodal imaging including spectral domain optical coherence tomography (SD-OCT).

Observations

We are comparing a case report of CT compared to that of NCMD. The case of a 64-year-old man with a lifelong history of decreased vision OD from toxoplasmosis and new onset of central retinal vein occlusion OS. Color fundus photography, spectral domain optical coherence tomography (SD-OCT), and intravenous fluorescein angiography (IVFA) were used as diagnostic imaging tools to demonstrate the similarities and differences between CT and NCMD. In this case, unilateral CT demonstrated a large, excavated, coloboma-like chorioretinal lesion identical to NCMD grade 3. Serology studies were positive for toxoplasmosis. The similarities of CT and NCMD grade 3 using SD-OCT are especially striking.

Conclusion and importance

Lesions of CT and NCMD grade 3 can appear identical on clinical exam and are indistinguishable from one another on SD-OCT. Because CT is a phenocopy of NCMD, many cases of the original NCMD family members had been misdiagnosed as CT. North Carolina Macular Dystrophy may be more common than previously realized and bilateral CT cases should be reexamined along with family members and genetic testing performed. Cases of bilateral CT actually may be NCMD cases. Now that the genetic and molecular mechanisms of NCMD are known, these may provide clues into the pathogenesis of CT.

SUBMITTER: Small KW

PROVIDER: S-EPMC6656702 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Publications

Congenital toxoplasmosis as one phenocopy of North Carolina Macular Dystrophy (NCMD/MCDR1).

Small Kent W KW Vincent Andrea L AL Knapper Chelsey L CL Shaya Fadi S FS

American journal of ophthalmology case reports 20190716

<h4>Purpose</h4>To highlight the striking similarities between the lesions of congenital toxoplasmosis (CT) and North Carolina Macular Dystrophy (NCMD) using multimodal imaging including spectral domain optical coherence tomography (SD-OCT).<h4>Observations</h4>We are comparing a case report of CT compared to that of NCMD. The case of a 64-year-old man with a lifelong history of decreased vision OD from toxoplasmosis and new onset of central retinal vein occlusion OS. Color fundus photography, s ...[more]

PMID: 31367689

Similar Datasets

Project description:To describe the phenotype of a family with an autosomal dominant macular dystrophy and identify the chromosomal location of the gene that causes this phenotype.Twelve members of a three-generation family underwent routine clinical examination, including fundus photography. Four of the patients underwent extended examination with Goldmann perimetry, full-field electroretinogram, dark adaptation, and color vision testing, and two patients underwent optical coherence tomography and fundus autofluorescence examination. DNA samples were obtained from 12 family members and 3 spouses and genotyped at the known North Carolina Macular Dystrophy (NCMD) locus on chromosome 6q (MCDR1: OMIM 136550) using short tandem repeat polymorphisms. DNA samples were subsequently examined with a genome-wide scan of single nucleotide polymorphisms and the genotypes that were produced were studied with linkage and haplotype analyses.The 10 affected family members had clinical findings of macular lesions that are typical for NCMD. The small drusen-like yellowish lesions of mild NCMD were hyperautofluorescent. Hyperpigmented foveal lesions were surrounded by a zone of confluent hyperautofluorescence. Linkage analysis of short tandem repeat polymorphism genetic markers excluded the NCMD locus on chromosome 6. However, analysis of single nucleotide polymorphism genotypes from a genome-wide scan showed that NCMD in our pedigree is linked to a region on chromosome 5p that overlaps the previously mapped macular dystrophy (MCDR3) locus with a maximum log of the odds (LOD) score of 2.69 at a recombination fraction of 0.00 (markers D5S406, D5S1987, and D5S2505).We report the first pedigree with NCMD from Scandinavia, and the first confirmation that a gene for this condition is located on chromosome 5p13-p15. The bright elements or lesions typical of NCMD differed from drusen in that no sign of accumulation of material between the retinal pigment epithelium and Bruch's membrane was seen. While the present study has found indications that the elements are located in the outermost layers of the retina, their precise location remains to be identified directly.

Project description:PurposeTo identify specific mutations causing North Carolina macular dystrophy (NCMD).DesignWhole-genome sequencing coupled with reverse transcription polymerase chain reaction (RT-PCR) analysis of gene expression in human retinal cells.ParticipantsA total of 141 members of 12 families with NCMD and 261 unrelated control individuals.MethodsGenome sequencing was performed on 8 affected individuals from 3 families affected with chromosome 6-linked NCMD (MCDR1) and 2 individuals affected with chromosome 5-linked NCMD (MCDR3). Variants observed in the MCDR1 locus with frequencies <1% in published databases were confirmed using Sanger sequencing. Confirmed variants absent from all published databases were sought in 8 additional MCDR1 families and 261 controls. The RT-PCR analysis of selected genes was performed in stem cell-derived human retinal cells.Main outcome measuresCo-segregation of rare genetic variants with disease phenotype.ResultsFive sequenced individuals with MCDR1-linked NCMD shared a haplotype of 14 rare variants spanning 1 Mb of the disease-causing allele. One of these variants (V1) was absent from all published databases and all 261 controls, but was found in 5 additional NCMD kindreds. This variant lies in a DNase 1 hypersensitivity site (DHS) upstream of both the PRDM13 and CCNC genes. Sanger sequencing of 1 kb centered on V1 was performed in the remaining 4 NCMD probands, and 2 additional novel single nucleotide variants (V2 in 3 families and V3 in 1 family) were identified in the DHS within 134 bp of the location of V1. A complete duplication of the PRDM13 gene was also discovered in a single family (V4). The RT-PCR analysis of PRDM13 expression in developing retinal cells revealed marked developmental regulation. Next-generation sequencing of 2 individuals with MCDR3-linked NCMD revealed a 900-kb duplication that included the entire IRX1 gene (V5). The 5 mutations V1 to V5 segregated perfectly in the 102 affected and 39 unaffected members of the 12 NCMD families.ConclusionsWe identified 5 rare mutations, each capable of arresting human macular development. Four of these strongly implicate the involvement of PRDM13 in macular development, whereas the pathophysiologic mechanism of the fifth remains unknown but may involve the developmental dysregulation of IRX1.

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Dataset Information

Congenital toxoplasmosis as one phenocopy of North Carolina Macular Dystrophy (NCMD/MCDR1).

Purpose

Observations

Conclusion and importance

Publications

Congenital toxoplasmosis as one phenocopy of North Carolina Macular Dystrophy (NCMD/MCDR1).

Similar Datasets

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