PMID:11138009

Citation	Bolz, H, von Brederlow, B, Ramírez, A, Bryda, EC, Kutsche, K, Nothwang, HG, Seeliger, M, del C-Salcedó Cabrera, M, Vila, MC, Molina, OP, Gal, A and Kubisch, C (2001) Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D. Nat. Genet. 27:108-12
Abstract	Usher syndrome type I (USH1) is an autosomal recessive disorder characterized by congenital sensorineural hearing loss, vestibular dysfunction and visual impairment due to early onset retinitis pigmentosa (RP). So far, six loci (USH1A-USH1F) have been mapped, but only two USH1 genes have been identified: MYO7A for USH1B and the gene encoding harmonin for USH1C. We identified a Cuban pedigree linked to the locus for Usher syndrome type 1D (MIM 601067) within the q2 region of chromosome 10). Affected individuals present with congenital deafness and a highly variable degree of retinal degeneration. Using a positional candidate approach, we identified a new member of the cadherin gene superfamily, CDH23. It encodes a protein of 3,354 amino acids with a single transmembrane domain and 27 cadherin repeats. In the Cuban family, we detected two different mutations: a severe course of the retinal disease was observed in individuals homozygous for what is probably a truncating splice-site mutation (c.4488G-->C), whereas mild RP is present in individuals carrying the homozygous missense mutation R1746Q. A variable expression of the retinal phenotype was seen in patients with a combination of both mutations. In addition, we identified two mutations, Delta M1281 and IVS51+5G-->A, in a German USH1 patient. Our data show that different mutations in CDH23 result in USH1D with a variable retinal phenotype. In an accompanying paper, it is shown that mutations in the mouse ortholog cause disorganization of inner ear stereocilia and deafness in the waltzer mouse.
Links	PubMed Online version:10.1038/83667
Keywords	Alternative Splicing/genetics; Amino Acid Sequence; Animals; Base Sequence; Cadherins/chemistry; Cadherins/genetics; Cadherins/metabolism; Cloning, Molecular; Consensus Sequence/genetics; Cuba; DNA Mutational Analysis; Exons/genetics; Female; Genotype; Germany; Hearing Loss, Sensorineural/genetics; Humans; Male; Molecular Sequence Data; Multigene Family/genetics; Mutation/genetics; Pedigree; Phenotype; RNA Splice Sites/genetics; RNA, Messenger/analysis; RNA, Messenger/genetics; Reverse Transcriptase Polymerase Chain Reaction; Syndrome
edit table

Annotations

Gene product	Qualifier	GO ID	GO term name	Evidence Code	with/from	Aspect	Notes	Status
edit table

References

See Help:References for how to manage references in GONUTS.