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A failure in optic fissure fusion during development can lead to blinding malformations of the eye. Here, we report a syndrome characterized by facial dysmorphism, colobomatous microphthalmia, ptosis and syndactyly with or without nephropathy, associated with homozygous frameshift mutations in FAT1. We show that Fat1 knockout mice and zebrafish embryos homozygous for truncating fat1a mutations exhibit completely penetrant coloboma, recapitulating the most consistent developmental defect observed in affected individuals. In human retinal pigment epithelium (RPE) cells, the primary site for the fusion of optic fissure margins, FAT1 is localized at earliest cell-cell junctions, consistent with a role in facilitating optic fissure fusion during vertebrate eye development. Our findings establish FAT1 as a gene with pleiotropic effects in human, in that frameshift mutations cause a severe multi-system disorder whereas recessive missense mutations had been previously associated with isolated glomerulotubular nephropathy., Loss of the cadherin FAT1 has been associated with nephropathy and epithelial cell adhesion defects. Here, the authors report five families with a syndromic form of coloboma associated with homozygous frameshift variants in FAT1 and recapitulate the phenotype in mutant mice and zebrafish.

Background Corneal dystrophies (CDs) are a heterogeneous group of bilateral, genetically determined, noninflammatory bilateral corneal diseases that are usually limited to the cornea. CD is characterized by a large variability in the age of onset, evolution and visual impact and the accumulation of insoluble deposits at different depths in the cornea. Clinical symptoms revealed bilateral multiple superficial, epithelial, and stromal anterior granular opacities in different stages of severity among three patients of this family. A total of 99 genes are involved in CDs. The aim of this study was to identify pathogenic variants causing atypical corneal dystrophy in a large Moroccan family and to describe the clinical phenotype with severely different stages of evolution. Case presentation In this study, we report a large Moroccan family with CD. Whole-exome sequencing (WES) was performed in the three affected members who shared a phenotype of corneal dystrophy in different stages of severity. Variant validation and familial segregation were performed by Sanger sequencing in affected sisters and mothers and in two unaffected brothers. Whole-exome sequencing showed a novel heterozygous mutation (c.1772C > A; p.Ser591Tyr) in the TGFBI gene. Clinical examinations demonstrated bilaterally multiple superficial, epithelial and stromal anterior granular opacities in different stages of severity among three patients in this family. Conclusions This report describes a novel mutation in the TGFBI gene found in three family members affected by different phenotypic aspects. This mutation is associated with Thiel-Behnke corneal dystrophy; therefore, it could be considered a novel phenotype genotype correlation, which will help in genetic counselling for this family.

Background: Corneal dystrophy (CDs) is a heterogeneous group disease, genetically determined non-inflammatory bilateral corneal diseases (usually limited to the cornea). CD is characterized by a large variability in the age of onset, evolution and visual impact and the accumulation of insoluble deposits at different depths of the cornea. Clinical symptoms revealed bilaterally multiple superficial, epithelial, and stromal anterior granular opacities, in different stages of severity among three patients of this family. 99 genes are involved in (CDs).The aim of this study is to identify pathogenic variant caused atypical corneal dystrophy in a large Moroccan family and to describe the clinical phenotype with their severe different stages of evolution.Methods: In this study, we report a large Moroccan family with fourteen individuals affected by corneal dystrophy. Whole Exome Sequencing (WES) was performed in the propositus (IV-7) which had corneal pain since the age of 18, associated with a decrease in visual acuity with anterior epithelial and stromal corneal dystrophy, in the form of microvacuole and poorly individualized anterior opacities, with fuzzy edges and an unevenness of the epithelial layers taking the sawtooth appearance. The familial segregation was done by Sanger sequencingResults: Whole exome sequencing showed a novel heterozygous mutation (c.1772C>A; p.Ser591Tyr) in TGFBI gene. Clinical examinations demonstrated bilaterally multiple superficial, epithelial and stromal anterior granular opacities; in different stages of severity among three patients of this family. Conclusions: This report presents a novel mutation in TGFBI gene, found in all family members affects with different phenotypic aspects. This mutation is associated with Thiel-Behnke corneal dystrophy and therefore, it could be considered as a novel phenotype genotype correlation, which will help in genetic counseling for this family

Heimler syndrome (HS) is a rare recessive disorder characterized by sensorineural hearing loss (SNHL), amelogenesis imperfecta, nail abnormalities, and occasional or late-onset retinal pigmentation. It is the mildest form known to date of peroxisome biogenesis disorder caused by hypomorphic mutations of PEX1 and PEX6 genes. We report on a second Moroccan family with Heimler syndrome with early onset, severe visual impairment and important phenotypic overlap with Usher syndrome. The patient carried a novel homozygous missense variant c.3140T > C (p.Leu1047Pro) of PEX1 gene. As standard biochemical screening of blood for evidence of a peroxisomal disorder did not provide a diagnosis in the individuals with HS, patients with SNHL and retinal pigmentation should have mutation analysis of PEX1 and PEX6 genes.

Une contusion du globe peut se compliquer de rupture de la membrane de Bruch ou de la choroïde. Cette complication est observée dans 5 à 10% des cas avec une nette prédominance masculine. Nous rapportons l'observation clinique d'un patient de 26 ans, victime d'un traumatisme contusif sévère de l'œil gauche chez qui l'examen retrouve une rupture de la membrane de bruch au fond d'œil ; l'evolution spontanné a été marquée par une amélioration visuelle sans complications néovasculaires. Au cours des ruptures post traumatiques de la membrane de bruch le pronostic est essentiellement lié d'une part à sa localisation par rapport à la macula; et d'autre part à la survenue de complications néovasculaires (15 à 30 % des cas).

La dacryoadenite tuberculeuse est une inflammation rare de la glande lacrymale cause par le bacille Mycobacterium tuberculosis. Elle pose un probleme etiopathogenique et diagnostique. Nous rapportons dans cette observation le cas d'une dacryoadenite tuberculeuse bilaterale chez un jeune homme Marocain de 34 ans ayant presente une tuberculose ganglionnaire et du cavum il y a 14 ans, ayant ete confirme par l'examen anatomopathologique. La tuberculose reste un diagnostic qui doit etre toujours evoque meme dans les atteinte bilaterale surtout si il y a un antecedent personnel ou familiale positif de tuberculose. Le pronostic de cette affection est devenu favorable grâce au traitement antibacillaire precoce.

La dacryoadénite tuberculeuse est une inflammation rare de la glande lacrymale causé par le bacille Mycobacterium tuberculosis. Elle pose un problème étiopathogénique et diagnostique. Nous rapportons dans cette observation le cas d'une dacryoadénite tuberculeuse bilatérale chez un jeune homme Marocain de 34 ans ayant présenté une tuberculose ganglionnaire et du cavum il y à 14 ans, ayant été confirmé par l'examen anatomopathologique. La tuberculose reste un diagnostic qui doit être toujours évoqué même dans les atteinte bilatérale surtout si il y a un antécédent personnel ou familiale positif de tuberculose. Le pronostic de cette affection est devenu favorable grâce au traitement antibacillaire précoce.