Loss of function of RIMS2 causes a syndromic congenital cone-rod synaptic disease with neurodevelopmental and pancreatic involvement

Congenital cone-rod synaptic disorder (CRSD), also known as incomplete congenital stationary night blindness (iCSNB), is a non-progressive inherited retinal disease (IRD) characterized by night blindness, photophobia, and nystagmus, and distinctive electroretinographic features. Here, we report bi-allelic RIMS2 variants in seven CRSD-affected individuals from four unrelated families. Apart from CRSD, neurodevelopmental disease was observed in all affected individuals, and abnormal glucose homeostasis was observed in the eldest affected individual. RIMS2 regulates synaptic membrane exocytosis. Data mining of human adult bulk and single-cell retinal transcriptional datasets revealed predominant expression in rod photoreceptors, and immunostaining demonstrated RIMS2 localization in the human retinal outer plexiform layer, Purkinje cells, and pancreatic islets. Additionally, nonsense variants were shown to result in truncated RIMS2 and decreased insulin secretion in mammalian cells. The identification of a syndromic stationary congenital IRD has a major impact on the differential diagnosis of syndromic congenital IRD, which has previously been exclusively linked with degenerative IRD

Lettre de Louis Phélypeaux de Pontchartrain (chancelier de France) à Jean Bacquet et Théophile Doroz (avocats généraux au parlement de Besançon) datée du 22 janvier 1702, à Versailles

Lettre de Louis Phélypeaux de Pontchartrain (chancelier de France) à Jean Bacquet et Théophile Doroz (avocats généraux au parlement de Besançon) datée du 22 janvier 1702, à Versailles. In: Correspondance administrative sous le règne de Louis XIV, recueillie et mise en ordre par G. B. Depping. Tome II. Administration de la justice – Police – Galères. Paris : Imprimerie nationale, 1851. pp. 364-365

Lettre de Louis Phélypeaux de Pontchartrain (chancelier de France) à Jean Bacquet et Théophile Doroz (avocats généraux au parlement de Besançon) datée du 22 janvier 1702, à Versailles

Lettre de Louis Phélypeaux de Pontchartrain (chancelier de France) à Jean Bacquet et Théophile Doroz (avocats généraux au parlement de Besançon) datée du 22 janvier 1702, à Versailles. In: Correspondance administrative sous le règne de Louis XIV, recueillie et mise en ordre par G. B. Depping. Tome II. Administration de la justice – Police – Galères. Paris : Imprimerie nationale, 1851. pp. 364-365

Neither the patient nor the physician could see anything: Atypical Bing-Neel syndrome

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Destination Memory in Korsakoff's Syndrome

BACKGROUND: Context memory, or the ability to remember the context in which an episodic event has occurred (e.g., where and when an event took place), has been found to be compromised in Korsakoff's syndrome. This study examined whether a similar deficit would be observed for destination memory, that is, the ability to remember to whom an information was previously transmitted. METHODS: Patients with Korsakoff's syndrome and healthy controls were instructed to tell proverbs to pictures of celebrities. In a subsequent recognition test, they had to indicate to which celebrity they had previously told the proverbs. Participants also completed a neuropsychological battery including a binding task in which they were required to associate letters with their correspondent locations to assess context memory. RESULTS: Results showed worse binding and destination memory in patients with Korsakoff's syndrome than in controls. In the Korsakoff group, destination memory was significantly correlated with and predicted by performances on the binding task. CONCLUSIONS: The binding process seems to be impaired in Korsakoff's syndrome, a deficit that may account for the destination memory compromise in the syndrome, and probably, for the difficulty to retrieve the "where and when" of an encountered event

Neither the patient nor the physician could see anything: Atypical Bing-Neel syndrome

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Novel TTLL5 Variants Associated with Cone-Rod Dystrophy and Early-Onset Severe Retinal Dystrophy

International audienceVariants of the TTLL5 gene, which encodes tubulin tyrosine ligase-like family member five, are a rare cause of cone dystrophy (COD) or cone-rod dystrophy (CORD). To date, only a few TTLL5 patients have been clinically and genetically described. In this study, we report five patients harbouring biallelic variants of TTLL5. Four adult patients presented either COD or CORD with onset in the late teenage years. The youngest patient had a phenotype of early onset severe retinal dystrophy (EOSRD). Genetic analysis was performed by targeted next generation sequencing of gene panels and assessment of copy number variants (CNV). We identified eight variants, of which six were novel, including two large multiexon deletions in patients with COD or CORD, while the EOSRD patient harboured the novel homozygous p.(Trp640*) variant and three distinct USH2A variants, which might explain the observed rod involvement. Our study highlights the role of TTLL5 in COD/CORD and the importance of large deletions. These findings suggest that COD or CORD patients lacking variants in known genes may harbour CNVs to be discovered in TTLL5, previously undetected by classical sequencing methods. In addition, variable phenotypes in TTLL5-associated patients might be due to the presence of additional gene defects