Splicing mutations of 54-bp exons in the COL11A1 gene cause Marshall syndrome, but other mutations cause overlapping Marshall/Stickler phenotypes

Stickler and Marshall syndromes are dominantly inherited chondrodysplasias characterized by midfacial hypoplasia, high myopia, and sensorineural-heari ng deficit. Since the characteristics of these syndromes overlap, it has be en argued whether they are distinct entities of different manifestations of a single syndrome. Several mutations causing Stickler syndrome have been f ound in the COL2A1 gene, and one mutation causing Stickler syndrome and one causing Marshall syndrome have been detected in the COL11A1 gene. We chara cterize here the genomic structure of the COL11A1 gene. Screening of patien ts with Stickler, Stickler-like, or Marshall syndrome pointed to 23 novel m utations. Genotypic-phenotypic comparison revealed an association between t he Marshall syndrome phenotype and splicing mutations of 54-bp exons in the C-terminal region of the COL11A1 gene. Null-allele mutations in the COL2A1 . gene led to a typical phenotype of Stickler syndrome. Some patients, howe ver, presented with phenotypes of both Marshall and Stickler syndromes.