Two Finnish USH1B patients with three novel mutations in myosin VIIA.
OBJECTIVE
Usher syndrome (USH) is an autosomal recessive disorder resulting in retinal degeneration and sensorineural deafness caused by mutations in at least 10 gene loci. USH is divided into three main clinical types: USH1 (33-44%), USH2 (56-67%), and USH3. Worldwide, USH1 and USH2 account for most of the Usher syndrome cases with rare occurrence of USH3. In Finland, however, USH3 is the most common type (40%), explained by genetic and geographical isolation accompanied with a founder mutation, while USH1 is estimated to comprise 34% and USH2 12% of all USH cases.


METHODS
We examined two unrelated Finnish USH1 patients by sequencing.


RESULTS
We found three new myosin VIIA (MYO7A) mutations: p.K923AfsX8, p.Q1896X, and p.E1349K. The p.K923AfsX8 mutation was present in both patients as well as in one of 200 Finnish control chromosomes.


CONCLUSIONS
This is the first molecular genetic study of USH1 in Finland. We have found three new pathological mutations causing either premature termination of translation or replacement of an evolutionary conserved MYO7A amino acid.
Vastinsalo
Hanna
H
Folkhälsan Institute of Genetics, Biomedicum Helsinki, Helsinki, Finland. hanna.vastinsalo@helsinki.fi
Isosomppi
Juha
J
Aittakorpi
Anne
A
Sankila
Eeva-Marja
EM
D019943:Amino Acid Substitution; D018389:Codon, Nonsense; D004398:Dyneins / Q000235:genetics*; D005260:Female; D005387:Finland; D016368:Frameshift Mutation; D017353:Gene Deletion; D018698:Glutamic Acid; D005973:Glutamine; D006579:Heterozygote; D006801:Humans; D008239:Lysine; D008297:Male; D009154:Mutation; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics*; D010375:Pedigree; D052245:Usher Syndromes / Q000235:genetics*
D018389:Codon, Nonsense; C000631455:MYO7A protein, human; D000081412:Myosin VIIa; D005973:Glutamine; D018698:Glutamic Acid; D009218:Myosins; D004398:Dyneins; D008239:Lysine