%0 Journal Article %T Major intra-familial phenotypic heterogeneity and incomplete penetrance due to a CACNA1A pathogenic variant %+ U 1211 Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (MRGM) %+ Service de Génétique Médicale du CHU de Bordeaux %+ Département de Neuro-Radiologie [Bordeaux] (DNR - Bordeaux) %+ Service de génétique médicale CHU Grenoble Hôpital Couple Enfant %+ Dynamiques Cellulaire et Tissulaire - Interdisciplinarité, Modélisation & Microscopie (TIMC-IMAG-DyCTiM2) %+ Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon) %+ Service de génétique moléculaire neurovasculaire, groupe hospitalier Saint-Louis Lariboisière-Fernand-Widal, 75010 Paris, France. %+ Service de neurologie [Bordeaux] %+ Hôpital Lariboisière-Fernand-Widal [APHP] %+ Service de génétique médicale - Unité de génétique clinique [Nantes] %A Angelini, Chloé %A van Gils, Julien %A Bigourdan, Antoine %A Jouk, Pierre-Simon %A Lacombe, Didier %A Ménégon, Patrice %A Moutton, Sébastien %A Riant, Florence %A Sole, Guilhem %A Tournier-Lasserve, Elisabeth %A Trimouille, Aurelien %A Vincent, Marie %A Goizet, Cyril %Z IF 2.004 (2017) %< avec comité de lecture %@ 1769-7212 %J European Journal of Medical Genetics %I Elsevier %8 2018 %D 2018 %R 10.1016/j.ejmg.2018.08.011 %M 30142438 %K Ataxia %K CACNA1A %K Epileptic encephalopathy %K Genetic counselling %K Incomplete penetrance %Z Life Sciences [q-bio]/Genetics/Human geneticsJournal articles %X The CACNA1A gene encodes a calcium-dependent voltage channel, localized in neuronal cells. Pathogenic variants in this gene are known to lead to a broad clinical spectrum including episodic ataxia type 2, spinocerebellar ataxia type 6, familial hemiplegic migraine, and more recently epileptic encephalopathy. We report a large family revealing a wide variability of neurological manifestations associated with a CACNA1A missense pathogenic variant. The index case had early-onset epileptic encephalopathy with progressive cerebellar atrophy, although his mother and his great-grandmother suffered from paroxystic episodic ataxia. His grandfather and great grand-aunt reported no symptoms, but two of her sons displayed early-onset ataxia with intellectual disability. Two of her little daughters suffered from gait disorders, and also from epilepsy for one of them. All these relatives were carriers of the previously described heterozygous variant in CACNA1A gene. We report here the first family leading to major clinical variability and incomplete penetrance. Our family highlights the difficulties to provide accurate genetic counselling concerning prenatal diagnosis regarding highly variable severity of the clinical presentation. %G English %2 https://u-bourgogne.hal.science/hal-01952641/document %2 https://u-bourgogne.hal.science/hal-01952641/file/S1769721218303355.pdf %L hal-01952641 %U https://u-bourgogne.hal.science/hal-01952641 %~ UNIV-NANTES %~ UNIV-BOURGOGNE %~ UGA %~ IMAG %~ CNRS %~ INPG %~ APHP %~ TIMC-IMAG %~ TIMC-IMAG-DYCTIM %~ LNC-UMR866 %~ LNC-GAD %~ UNIV-LYON %~ UGA-COMUE %~ ELSEVIER %~ NANTES-UNIVERSITE %~ UNIV-NANTES-AV2022