The cloning and developmental expression of unconventional myosin IXA (MYO9A) a gene in the Bardet-Biedl syndrome (BBS4) region at chromosome 15q22-q23

Bardet-Biedl Syndrome (BBS) is a heterogeneous, autosomal recessive disorde r characterized by mental retardation, obesity, retinitis pigmentosa, synda ctyly and/or polydactyly, short stature, and hypogenitalism and is caused b y mutations at a number of distinct loci. Using a positional cloning approa ch for identifying the BBS4 (chromosome 15) gene, we identified and cloned an unconventional myosin gene, myosin MA (HGMW-approved symbol MYO9A). Sinc e mutations in unconventional myosins are known to cause several human dise ases, and since mutations of unconventional myosin VIIa cause retinal degen eration, we evaluated myosin MA as a candidate for BBS. We exploited PCR-ba sed techniques to clone a 8473-nt cDNA for myosin IXA.A 7644-bp open readin g frame predicts a protein with all the hallmarks of class IX unconventiona l myosins. Human Northern blot analysis and in situ hybridization of mouse embryos reveal that myosin MA is expressed in many tissues consistent with BBS. Intron/exon boundaries were identified, and myosin MA DNA and RNA from BBS4 patients were evaluated for mutation. (C) 1999 Academic Press.