CHAMP1 Mutations cause Refractory Infantile Myoclonic EpilepsyFunding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
22 March 2019 (eFirst)
The chromosome alignment maintaining phosphoprotein 1 (CHAMP1) gene has a key role in neurodevelopment. It is involved in kinetochore-microtubule attachment and in the regulation of chromosomes alignment during mitosis. So far, 17 cases of CHAMP1 mutations have been reported with a common clinical picture of developmental delay and intellectual disability, dysmorphic facial features, hypotonia and/or spasticity, and microcephaly. Four patients had epilepsy of whom three had focal seizures and one had generalized epilepsy. We report two new cases, which have in addition to developmental delay, refractory myoclonic epilepsy. These cases suggest that the phenotypic spectrum of CHAMP1 mutations may be broader and includes refractory myoclonic epilepsy as well.
- 1 Itoh G, Kanno S, Uchida KS. , et al. CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment. EMBO J 2011; 30 (01) 130-144
- 2 Hempel M, Cremer K, Ockeloen CW. , et al. De novo mutations in CHAMP1 cause intellectual disability with severe speech impairment. Am J Hum Genet 2015; 97 (03) 493-500
- 3 Deciphering Developmental Disorders Study. Large-scale discovery of novel genetic causes of developmental disorders. Nature 2015; 519 (7,542): 223-228
- 4 Tanaka AJ, Cho MT, Retterer K. , et al. De novo pathogenic variants in CHAMP1 are associated with global developmental delay, intellectual disability, and dysmorphic facial features. Cold Spring Harb Mol Case Stud 2016; 2 (01) a000661
- 5 Isidor B, Küry S, Rosenfeld JA. , et al. De novo truncating mutations in the kinetochore-microtubules attachment gene CHAMP1 cause syndromic intellectual disability. Hum Mutat 2016; 37 (04) 354-358
- 6 Okamoto N, Tsuchiya Y, Kuki I. , et al. Disturbed chromosome segregation and multipolar spindle formation in a patient with CHAMP1 mutation. Mol Genet Genomic Med 2017; 5 (05) 585-591