These are the genes we don’t need – or do we?

Rare human knockouts. Recessive disorders arise when both copies of a causative gene are affected by mutations. These diseases are thought to be a very rare occurrence, but the cumulative impact of these conditions is not known. Population genome sequencing offers the possibility to assess the spectrum and distribution of potentially causative mutations in large groups of individuals. In a recent publication from deCODE published in Nature Genetics, the authors examine the population spectrum of rare human knockouts using the unique genetic data and population structure of the Icelanders. Here is the story about potential candidate genes identified by population genetics. Continue reading

Rare Epilepsy Syndromes and the Congenital Disorders of Glycosylation

Rare Epilepsy Syndromes. Motivated by a recent paper in JIMD Reports, I wanted to use this post to present a very rare group of disorders, in which glycosylation of a variety of tissue proteins and/or lipids is deficient. These so-called congenital disorders of glycosylation (CDG) are a highly heterogeneous group of recessive disorders that you might be confronted with. As CDG may masquerade as otherwise non-specific epileptic encephalopathies, you might encounter them clinically or by browsing through exomes of patients with RES. Imtiaz and colleagues now report on two brothers in a large Saudi family with 18 affected siblings. They identified a mutation in DPAGT1, which is known to cause CDG Ij.   Continue reading