Abstract Stickler and Marshall syndromes are genetic disorders both inherited in an autosomal dominant manner. The genotype-phenotype correlation was performed in ten Stickler/Marshall syndrome patients with mutations in the COL11A1 gene. Four patients had a phenotype classified as Marshall syndrome based on early-onset severe hearing loss and characteristic facial dysmorphism. A splice site mutation in intron 50 of COL11A1 was found in these patients, while the remaining six patients had an overlapping Marshall-Stickler phenotype with a mutation elsewhere in the gene. These results indicate exon 50 as a hot spot for splice site mutations leading to a phenotype of Marshall syndrome rather than Stickler syndrome. Collagen II (COL2A1) precursor mRNA undergoes alternative splicing resulting in two different isoforms, IIA including exon 2 and IIB excluding exon 2. Recent evidence indicates that premature termination codon mutations in exon 2 cause Stickler syndrome with no or minimal extraocular manifestations. Two mutations were observed in this study: Cys64Stop, and a novel structural mutation, Cys57Tyr. Results from the COL2A1 mini-gene studies suggested that both mutations altered positive cis elements for splicing resulting in a lower IIA:IIB ratio. The results further emphasize the importance of exon 2 in the development and normal function of the eye. In addition, patients displaying eye phenotypes in the absence of extraocular manifestations should be analyzed first for exon 2 mutations. Linkage analysis identified a new locus for autosomal recessive nonsyndromic hearing loss (DFNB32) on chromosome 1p13.3-22.1 in a Tunisian family with congenital profound autosomal recessive deafness. The COL11A1 gene is located in this region and was analyzed as a candidate gene. No disease causing sequence variation was observed. The analysis of 85 English and 40 Finnish subjects with high myopia resulted in the identification 23 sequence variations in the SLRP genes LUM, FMOD, PRELP, and OPTC. The two intronic variations and seven amino acid changes, one synonymous and six non-synonymous, were not found in the 308 controls analyzed. Five changes were detected in opticin, and all but one were shown to co-segregate with high myopia in families with incomplete penetrance. The results suggested that sequence variations in the SLRP genes expressed in the eye are genetic risk factors underlying the pathogenesis of high myopia.

Deafblindness is a combined impairment of vision and hearing with an incidence of about 1: 8000 children and 1: 5500 adults. The most common genetic causes are the Stickler (STL) and Usher (USH) syndromes. The main goal of this work is to provide an up-to-date overview of STL and USH in the Czech and Slovak Republic (CR and SR), to determine the correlations between the genotype and phenotype in our population and the associated diagnostic criteria. Using sequencing and MLPA we examined 45 patients from 28 families for suspected STL. We found potentially causal variants of STL genes in 39 patients from 22 families. Fifteen different COL2A1 variants (8 being novel) were found in 28 patients from 18 families and 4 novel COL11A1 variants were found in 11 patients from 4 families. We identified the cause of the disease in 79 % of the families. The USH study involved 30 patients from 27 families. The most frequent cause was USH2A pathogenic variants, i.e. 19 variants in 14 families, 9 being novel. Less common were pathogenic variants in MYO7A (6 variants in 3 families, 5 being novel), USH1C and CDH23 (3 variants, 2 being novel, in 2 families both) genes. In 2 families, compound heterozygosity was found for variants in two different USH genes. The deafblindness etiology was clarified for 24 patients from...