We identified eight LZTR1 variants, including a de novo variant, in seven probands who were suspicious for NS and one known de novo PPP1CB variant in a patient with NS.
MRAS, SHOC2, and PPP1CB are mutated in Noonan syndrome, and we show that syndromic mutations invariably promote complex formation with each other, but not necessarily with other interactors.
Noonan-like syndrome with loose anagen hair (NSLH, including NSLH1, OMIM #607721 and NSLH2, OMIM #617506) is characterized by typical features of NS with additional findings of macrocephaly, loose anagen hair, growth hormone deficiency in some, and a higher incidence of intellectual disability.
This report gives further support that this novel RASopathy-PPP1CB-related Noonan syndrome with loose anagen hair-shares great similarity to Noonan syndrome-like disorder with loose anagen hair, and expands the phenotypic spectrum by adding the cranial vault abnormality.