De novo pathogenic variants in CHAMP1 are associated with global developmental delay, intellectual disability, and dysmorphic facial features.


We identified five unrelated individuals with significant global developmental delay and intellectual disability (ID), dysmorphic facial features and frequent microcephaly, and de novo predicted loss-of-function variants in chromosome alignment maintaining phosphoprotein 1 (CHAMP1). Our findings are consistent with recently reported de novo mutations in CHAMP1 in five other individuals with similar features. CHAMP1 is a zinc finger protein involved in kinetochore-microtubule attachment and is required for regulating the proper alignment of chromosomes during metaphase in mitosis. Mutations in CHAMP1 may affect cell division and hence brain development and function, resulting in developmental delay and ID.





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Publication Info

Tanaka, Akemi J, Megan T Cho, Kyle Retterer, Julie R Jones, Catherine Nowak, Jessica Douglas, Yong-Hui Jiang, Allyn McConkie-Rosell, et al. (2016). De novo pathogenic variants in CHAMP1 are associated with global developmental delay, intellectual disability, and dysmorphic facial features. Cold Spring Harb Mol Case Stud, 2(1). p. a000661. 10.1101/mcs.a000661 Retrieved from

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Allyn McConkie-Rosell

Professor in Pediatrics

Undiagnosed disorders are often not amenable to the traditional diagnostic approaches and the lack of a diagnosis leads to repeated clinical consultations and laboratory testing, causing substantial personal and familial emotional and financial stress.  For parents of children with undiagnosed diseases, the extensive search for a diagnosis and inherent uncertainty surrounding their child’s health can result in stress, frustration and worries about worsening of symptoms and delays in treatment or inappropriate treatment.  As genetic testing becomes more advanced so do the expectations, associated uncertainty, and if diagnosed, an increased the frequency of a diagnosis of an ultra-rare disorder.  Thus, it is important to describe the complex emotional experience and the relationship to health care engagement and to follow this process in real time with parents as they are experiencing the diagnostic process in order to better understand their needs and to develop strategies to improve outcomes.  Challenges posed by WES for clinicians are largely by virtue of variation in the clinical relevance of results. For instance, many cases require clinical follow-up of variants of uncertain significance and secondary/incidental findings, and it has become necessary communicate effectively with patients/families at multiple stages to both educate and address expectations (pre-test counseling) and relay uncertain or less understood results (post-test counseling). Likewise, parents of children with rare disorders may be challenged to understand the process, the outcome, the certainty of the diagnosis; effectively communicate information to family members and providers; and use the new information to the benefit their of families.  Responsive to these shifting clinical needs, my research is focused on exploring how families manage genetic information with the goal of identifying genetic counseling strategies to facilitate their positive adaptation, coping, and use of information.  

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