CHAMP1 clinical spectrum (MRD40 – OMIM 616579)

Targeted gene(s)/phenotype under study : CHAMP1

Abstract :

A very small number of patients have been reported with heterozygous LOF variants in CHAMP1 (Tanaka 2016, Isidor 2016, Hempel 2015). CHAMP1 is involved in spindle assembly checkpoint, which assures proper kinetochore-microtubule attachment of all chromosomes prior to anaphase. LOF causes e.a. abnormal spindle orientation and formation of multipolar spindles. The patients present with hypotonia and joint laxity, microcephaly, moderate to severe intellectual disability with absent or very poor speech acquisition, and variable dysmorphism with, epicanthal folds, upslanting palpebral fissures, tented upper lip, everted lower lip and pointed chin. Mild brain atrophy, cerebellar cortical dysplasia and delayed myelination are seen. Departing from 2 local patients, we aim at building an European cohort of CHAMP1 patients, in order to better delineate the clinical spectrum, the neurodevelopmental profile and developmental brain anomalies, considering interactions of CHAMP1 with several MCPH genes.

Coordinating clinician/researcher: Pr Alain Verloes

Institution :

Department of Clinical Genetics,

APHP Rebert Debré University Hospital

75019 Paris

France

Contact : alain.verloes@aphp.fr

Specific requirements beyond clinical data and genotype data sharing:

  • Re-analysis of DNA samples : N
  • Resampling of patients : N
  • Linked to a translational/basic research project?