Joubert syndrome (JS) is a rare genetic ciliopathy, whose diagnostic hallmark is the “molar tooth sign” on brain MRI. Mutations in over 40 different genes can cause JS, many of which are involved in the proper functioning of primary cilia. HYLS1 gene is associated with a severe condition called Hydrolethalus syndrome, leading to early death. However, our study describes a patient with JS carrying biallelic mutations in this gene, suggesting that the variant localization might influence the severity of the disease. This finding helps us understand why mutations in the same gene can lead to different conditions. (By Dr. Fulvio D’Abrusco, https://jmg.bmj.com/content/62/1/3 )