Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity

Joubert syndrome (JS) is a recessive neurodevelopmental disorder characterized by hypotonia, ataxia, cognitive impairment, abnormal eye movements, respiratory control disturbances, and distinctive brain MRI findings. Diagnosis and treatment of JS is challenging due to >28 associated genes and substantial clinical variability. This study provides a relatively unbiased view of the phenotypic range, genetic basis, and gene-phenotype associations in >500 individuals with JS. This information is crucial for diagnostic and carrier testing, medical monitoring for progressive complications, and interpretation of variants identified through genome-wide sequencing results. Understanding the genetic basis of JS is facilitating the development of gene-specific treatments. (By Dr. Dan Doherty, http://jmg.bmj.com/content/52/8/514 )