Papers by Micheline Misrahi
PubMed, 1988
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Hépato-Gastro & Oncologie Digestive, Nov 24, 1997
La maladie de Wilson est une maladie genetique de transmission autosomique recessive. Bien avant ... more La maladie de Wilson est une maladie genetique de transmission autosomique recessive. Bien avant que le gene qui en est responsable ait ete identifie, il avait ete demontre que deux perturbations majeures du metabolisme du cuivre etaient a son origine, la diminution de l'excretion biliaire d'une part et la diminution de l'incorporation dans la ceruloplasmine d'autre part. La diminution de l'excretion biliaire du cuivre normalement absorbe conduit a une accumulation hepatique du cuivre, puis a une surcharge extra-hepatique principalement cerebrale. Les mecanismes de la toxicite du cuivre sont encore tres mal connus. La localisation du locus morbide sur le chromosome 13 a permis dans un premier temps de faire un diagnostic indirect dans la fratrie par analyse de liaison genetique. Le clonage du gene (ATP7B) a permis de montrer qu'il code une proteine de 1 411 acides amines appartenant a la famille des ATPases de type P. Le gene est de tres grande taille et comprend 21 exons. Les mutations retrouvees chez les malades sont dispersees. Cependant, dans les populations europeennes, certains exons sont plus frequemment impliques. Cela permet de proposer un diagnostic moleculaire direct de la maladie si les deux mutations sont identifiees chez un malade. Le diagnostic indirect par liaison genetique reste par contre le plus souvent necessaire dans la fratrie. Le developpement de sondes tres informatives permet d'obtenir une certitude dans la quasi-totalite des cas, meme chez les jeunes enfants ou en periode presymptomatique. Enfin, le clonage du gene homologue chez le rat et la mise en evidence d'une deletion de l'ATP7B chez le rat LEC va permettre de preciser les etapes du metabolisme normal du cuivre et le mecanisme de la maladie de Wilson.
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Nephrology Dialysis Transplantation, Jan 16, 2023
ABSTRACT Background Cardiac and neurological involvements are the main clinical features of hered... more ABSTRACT Background Cardiac and neurological involvements are the main clinical features of hereditary transthyretin (ATTRv) amyloidosis. Few data are available about ATTRv amyloid nephropathy (ATTRvN). Methods We retrospectively included 30 patients with biopsy-proven ATTRvN [V30M (26/30) including two domino liver recipients, S77Y (2/30), V122I (1/30) and S50R (1/30) variants] from two French reference centers. We described the pathological features by comparing amyloid deposits distribution to patients with AL or AA amyloidosis, and sought to determine clinicopathological correlation with known disease-modifying factors such as TTR variant, gender and age at diagnosis. Results In comparison with AL and AA amyloidosis, ATTRv patients had similar glomerular, arteriolar and arterial amyloid deposits, but more cortical and medullary tubulointerstitial (33%, 44%, 77%, P = .03) involvement. While the presence of glomerular deposits is associated with the range of proteinuria, some patients with abundant glomerular ATTRv amyloidosis had no significant proteinuria. V30M patients had more glomerular (100% and 25%, odds ratio = 114, 95% confidence interval 3.85–3395.00, P = .001) deposits, and higher estimated glomerular filtration rate [50 (interquartile range 44–82) and 27 (interquartile range 6–31) mL/min/1.73 m², P = .004] than non-V30M patients. We did not find difference in amyloid deposition according to gender or age at diagnosis. Conclusion ATTRvN affects all kidney compartments, but compared with AL/AA amyloidosis, ATTRvN seems to involve more frequently tubulointerstitial areas. V30M patients represents the dominant face of the disease with a higher risk of glomerular/arteriolar involvement. ATTRvN should thus be considered in patients, and potential relatives, with ATTRv amyloidosis and kidney dysfunction, regardless of proteinuria level.
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Fertility and Sterility, Aug 1, 2022
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PubMed, Mar 9, 1985
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Annales d'endocrinologie, 2001
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HAL (Le Centre pour la Communication Scientifique Directe), Oct 15, 2022
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Molecular Endocrinology, Mar 1, 2004
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Reproductive Biomedicine Online, 2012
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Human Reproduction
Study question Identify the genetic cause of a cohort of patients with unexplained Diminished ova... more Study question Identify the genetic cause of a cohort of patients with unexplained Diminished ovarian reserve (DOR) by next-generation sequencing and compare with pregnancy outcome. Summary answer A high-yield positive genetic diagnosis was obtained: 27% of cases. Defects of genes involved in DNA repair/meiosis appeared to have an unfavorable prognosis. What is known already Ten percent of women undergoing Medically Assisted Procreation-MAP have a DOR defined by an AMH level <1.2 and an antral follicle count (AFC) <5. However, most causes of DOR are unknown. There is no known criteria of success in MAP. Primary ovarian insufficiency (POI) corresponds to a complete cessation of ovarian function in 1-4% of women under 40 years. We have very recently shown in a large cohort of POI that a custom-made target next-generation sequencing (NGS) POI panel allowed a genetic diagnosis in 30% of unexplained POI and leads to personalized medicine (Heddar et al., EBioMedicine. 2022 doi: 10.1...
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SSRN Electronic Journal
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Reproduction humaine et hormones, Feb 16, 2008
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Context: Primary Ovarian insufficiency (POI) affects 1% of women under 40 years and leads most of... more Context: Primary Ovarian insufficiency (POI) affects 1% of women under 40 years and leads most often to definitive infertility with adverse health outcomes. Very recently, genes involved in DNA repair have been shown to cause POI. Objective: To identify the cause of a familial POI in a consanguineous Turkish family. Design: Exome sequencing was performed in the proposita and her mother. Chromosomal breaks were studied in lymphoblastoid cell lines treated with Mitomycin (MMC). Setting and patients: The proposita presented intra-uterine and post-natal growth retardation, multiple pilomatricomas in childhood and primary amenorrhea. She was treated with growth hormone (GH) from 14 to 18 years. Results: We identified a novel nonsense mutation in exon 9 of the minichromosome maintenance complex component 8 gene (MCM8) NM_001281522.1: c.925C>T/p.R309* yielding a truncated protein devoid of the 531 C-terminal residues. The mutation was homozygous in the daughter and heterozygous in the m...
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☯ These authors contributed equally to this work.
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OBJECTIVE: To study the impact of labelling of a referral center for FAP in France and creation o... more OBJECTIVE: To study the impact of labelling of a referral center for FAP in France and creation of a national network for FAP. BACKGROUND: FAP are disabling and life-threatening diseases which are due to endoneurial amyloid deposits and are secondary to a point mutation of transthyretin (TTR) gene with an autosomal dominant transmission. Met30TTR-FAP presents as a small fiber polyneuropathy(SF-PNP) in Portugal with an early onset ( DESIGN/METHODS: All patients with TTR-FAP diagnosed in regional centers and were referred to NNERF. General characteristics and phenotypes were specified. To assess the incidence of new cases of TTRFAP, their characteristics and geographic origin were specified in the (2008-2012) period. RESULTS: 1)There were 119 new cases of FAP,with a number of new cases/year that switched from 10 in 2008 to 40 in 2012, 2)the mean age was 59 years (22-89)and a Portuguese origin in 22%, 3)The number of TTR gene mutations identified reached 35 increasing by 7 with 3 new m...
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Cahier de Recherche du Groupe HEC, N°16
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European Journal of Medical Genetics, 2021
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Bulletin de l'Académie Nationale de Médecine, 2021
Resume L’infertilite est un probleme de sante public affectant ∼ 15% des couples dans le monde et... more Resume L’infertilite est un probleme de sante public affectant ∼ 15% des couples dans le monde et l’insuffisance ovarienne primitive, correspondant a l’arret de la fonction ovarienne avant 40 ans, est un syndrome majeur responsable d’infertilite chez la femme (1-3,7%). Plusieurs etudes epidemiologiques avaient montre l’existence d’une relation inverse entre l’âge de la menopause et la duree de survie des femmes, celles avec insuffisance ovarienne primitive ayant une duree de vie la plus courte. Cette observation, longtemps incomprise, a ete expliquee recemment par les progres spectaculaires de la genetique en particulier du sequencage nouvelle generation, qui ont permis l’identification de causes genetiques d’insuffisance ovarienne primitive. En effet, la famille majoritaire responsable est celle des genes de meiose et de reparation de l’ADN, certains etant aussi responsables de tumeurs/cancers. Des etudes d’association a l’echelle du genome entier ont confirme un lien genetique entre la variabilite physiologique de l’âge de la menopause et l’insuffisance ovarienne primitive, ce lien impliquant la famille des genes de reparation de l’ADN. Cette observation va bouleverser la prise en charge des patientes du fait de la possibilite de comorbidites et d’une diminution de l’esperance de vie. L’identification de cette sous-population de patientes est une priorite medicale et scientifique pour l’avenir et permettra de mieux comprendre les mecanismes communs impliques dans le vieillissement reproductif et la longevite.
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Papers by Micheline Misrahi