Review for "Refining the role of de novo protein truncating variants in neurodevelopmental disorders using population reference samples"

Completed on 13 May 2016 by Anna Need. Sourced from

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A really great paper, allowing us to further restrict the pool of likely contributing variants in case/ control studies of neuropsychiatric illnesses, and move a step closer to being able to provide clinical genetic diagnoses for some people with these conditions.

Are you able to find out whether the parents carrying the ANK2 and RGL1 variants have any neuropsychiatric phenotype, and whether it was de novo or inherited in them?

Also, when you calculated the rate of class 2 variants for schizophrenia, did you exclude the variants only seen in the EXaC patients with schizophrenia? Or should we assume that the real rate is a bit lower as some that seem to be class 2 are actually recurrent de novo mutations contributing to schizophrenia and absent in controls?

(N.B. Not sure if this is an appropriate comment for this forum but there seems to be a typo in Supplementary table 3, the rate for congenital heart disease is given as a fraction and as a percentage for schizophrenia).