Erratum: analysis of DNA elements that modulate myosin VIIa expression in humans.
Usher syndromeIb (USH1B), an autosomal recessive disorder caused by mutations in myosin VIIa (MYO7A), is characterized by congenital profound hearing loss, vestibular abnormalities and retinitis pigmentosa. Promoter elements in the 5 kb upstream of the translation start were identified using adult retinal pigment epithelium cells (ARPE-19) as a model system. A 160 bp minimal promoter within the first intron was active in ARPE-19 cells, but not in HeLa cells that do not express MYO7A. A 100 bp sequence, 5' of the first exon, and repeated with 90% homology within the first intron, appeared to modulate expression in both cell lines. Segments containing these elements were screened by heteroduplex analysis. No heteroduplexes were detected in the minimal promoter, suggesting that this sequence is conserved. A -2568 A>T transversion in the 5' 100 bp repeat, eliminating a CCAAT element, was found only in USH1B patients. However, in all 5 families, -2568 A>T was in cis with the same missense mutation in the myosin VIIa tail (Arg1240Gln), and 4 of the 5 families were Dutch. These observations suggest either 1) linkage disequilibrium or 2)that a combination of a promoter mutation with a less active myosin VIIa protein results in USH1B.
Orten
D J
DJ
Center for Hereditary Communication Disorders, Boys Town National Research Hospital Omaha, NE, USA. ortend@boystown.org
Weston
M D
MD
Kelley
P M
PM
Cremers
C W
CW
Wagenaar
M
M
Jacobson
S G
SG
Kimberling
W J
WJ
D019943:Amino Acid Substitution; D002460:Cell Line; D004398:Dyneins; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015810:Linkage Disequilibrium; D020125:Mutation, Missense; D000081412:Myosin VIIa; D009218:Myosins / Q000096:biosynthesis / Q000235:genetics*; D010375:Pedigree; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000378:metabolism; D013577:Syndrome; D015837:Vestibular Diseases / Q000235:genetics* / Q000378:metabolism
C000631455:MYO7A protein, human; D000081412:Myosin VIIa; D009218:Myosins; D004398:Dyneins