IL6ST and craniosynostosis: We recently described loss-of-function variants in IL6ST as a novel cause of autosomal recessive HIES with skeletal abnormalities.19,20 In order to understand the impact of IL6ST variants in patients with skeletal abnormalities, we screened for homozygous or compound heterozygous variants in IL6ST in a cohort of 467 unrelated patients with craniosynostosis, who were mutation negative after clinically driven genetic testing.19 We identified a homozygous variant (c.842G>A; p.R281Q) in a single patient of South Asian origin, hereafter referred to as PR281Q (Fig. 1a–c).