X-linked. Almost a decade ago, the former EuroEPINOMICS team was asked to perform a difficult task. We reviewed inherited variants in X-linked genes, trying to understand whether inherited variants are causative of neurodevelopmental disorders for one of our research studies. In most cases, we decided that we did not have enough evidence. How could we tell whether variants in genes such as HUWE1 or CNKSR2 that were transmitted from unaffected females to affected sons were disease-causing or not? I remembered my frustration when I came across a publication on the contribution of X-linked variants to neurodevelopmental disorders that was published last year. Continue reading
Tag Archives: DDX3X
Publications of the week: DDX3X, KCND3, and NAPB
Issue 11/2015. This issue of our publications of the week is about three novel genes that were published recently, including a relatively frequent cause of intellectual disability in females, a gene for spinocerebellar ataxia, and a mutation in a novel SNARE-complex associated protein. Continue reading
Sequencing for developmental disorders on a national level – the DDD(UK) study
DDD. It’s probably the most impressive of all exome sequencing studies of 2014 and I almost missed it. Late December last year, the Deciphering Developmental Disorders study was published in Nature, reporting the genetic findings in more than 1,000 patient-parent trios, which were collected in a systematic nation-wide approach in the United Kingdom and Ireland. The analysis of more than 1,600 de novo mutations in this cohort provides another fascinating view into the genetics of neurodevelopmental disorders, independently confirming the role of DNM1 and pointing out several genes that act through either activating or dominant-negative mutations. Let me guide you through a study that comes to the sobering conclusion that even entire nations are too small to understand the genetics of neurodevelopmental disease. Continue reading
