Exome sequencing corrects diagnosis in autosomal recessive disorders

The amazing powers of exome sequencing – a disclaimer. We have recently blogged frequently on the power of exome sequencing in monogenic disorders. Dixon-Salazar now describe in “Exome Sequencing Can Improve Diagnosis and Alter Patient Management” the usefulness of exome sequencing in disease identification in autosomal recessive disorders. Their overall yield is a novel gene discovery in 22/118 probands and a different diagnosis than the initial in 10/118 patients. While title and abstract suggest that exome sequencing is a cure-all improving patient diagnosis and altering patient management, it should be pointed out that this manuscript exclusively deals with autosomal recessive disorders. Only two novel genes out of 20 are described, leaving the reader with little chance to investigate their claim. Many of their families were selected from countries with a high consanguinity including Morocco, where state-of-the-art diagnostic facilities are difficult to access for some patients. The only change in patient management resulting from the altered diagnosis was stopping supplementary Vitamin E in a family with a SPG11 mutation previously thought to have ataxia with vitamin E deficiency. What the altered direction of therapy in a family with a newly identified a-mannosidase type 1 entails, is left for the reader to imagine. The corresponding reference refers to a paper on stem cell transplant as a definitive treatment option, which will probably not be a treatment option for this family from Islamabad, Pakistan. The paper rather shows that exome sequencing is of use in autosomal recessive disorders and might yield surprises. Continue reading