MyosinVIIAMutation Screening in189UsherSyndrome Type1Patients

Summary Usher syndrome type lb(USHiB) isanautosomal recessive disorder characterized bycongenital profound hearingloss, vestibular abnormalities, andretinitis pigmentosa. Thedisorder hasrecently beenshowntobe caused bymutations inthemyosin Vhagene(MYO7A) located onllql4. Inthecurrent study, apanel of189 genetically independent Usher Icases werescreened for thepresence ofmutations intheN-terminal coding portion ofthemotordomain ofMYO7Abyheteroduplex analysis of14exons. Twenty-three mutations were found segregating withthedisease in20families. Ofthe 23mutations, 13wereunique, and2ofthe13unique mutations (Arg2l2His andArg2l2Cys) accounted for thegreatest percentage ofobserved mutantalleles (8/ 23,31%).Sixofthe13mutations caused premature stopcodons, 6caused changes intheaminoacid sequence ofthemyosin VI1aprotein, and1resulted in asplicing defect. Three patients werehomozygotes or compound heterozygotes formutant alleles; these three cases wereTyr333Stop/Tyr333Stop, Arg212HisArg3O2His/Arg212His-Arg3O2His, andIVS13nt-8c-/ Glu450Gln. Alltheother USHlBmutations observed weresimple heterozygotes, anditispresumed that the mutation ontheother allele ispresent intheunscreened regions ofthegene. Noneofthemutations reported here wereobserved in96unrelated control samples, although several polymorphisms weredetected. These results add three patients tosingle casereported previously where mutations havebeenfound inbothalleles andraises the total number ofunique mutations inMYO7Ato16.