Exome sequencing pipeline for rare Mendelian disorders: abetalipoproteinemia as a case study

We report our platform for exome sequencing analysis to discover candidate genes for rare metabolic lipid diseases. We have tested the pipeline in a family with abetalipoproteinemia. This disease is characterized by very low plasma concentrations of triglyceride and cholesterol (under 30mg/dl), and undetectable levels of LDL and apoB. Later in life, this disease is associated with atypical development of retinitis pigmentosa, coagulopathy, column neuropathy and myopathy.

In collaboration with the pediatrics unit of Hospital Clínico of Valencia, our group has studied a family with two affected children with the disease, and their healthy parents, without mutations in APOB, MTTP, PCSK9 and ANGPTL3 genes (discarded by Sanger sequencing).

During the set up of the pipeline we have compared different programs and pipelines, and validated the automatic variation calling against Sanger sequencing as a gold standard genotyping