(2011) identified 12 different homozygous CDH23 missense mutations, including 8 novel mutations, in 13 families with DFNB12. In contrast, homozygous nonsense, frameshift, splice site and some missense mutations of CDH23, or a combination of these USH1D alleles in a compound heterozygote, cause USH1D. Nonsyndromic DFNB12 deafness is associated with CDH23 missense mutations that are presumed to be hypomorphic alleles with sufficient residual activity for retinal and vestibular function, but not for auditory cochlear function. (2005) has been reclassified as a variant of unknown significance see 605516.0013. The T1209A variant reported by Zheng et al. (The CDH23 T1209A mutation was later reclassified as a variant of unknown significance.) All mutations were considered pathogenic because of their location in functionally important and evolutionarily conserved domains and their absence in 100 unrelated controls. The CDH23 T1209A mutation had been identified in USH1D patients, and the authors suggested that the more severe phenotype in this patient was due to a modifier effect of the PCDH15 5601delAAC mutation. The third proband was heterozygous for the same in-frame deletion in PCDH15 as the first proband, and homozygous for a previously identified missense mutation in CDH23 (T1209A 605516.0013). The second proband was heterozygous for a 16delT mutation in PCDH15 ( 605514.0008) and a missense mutation in CDH23 (R3189W 605516.0012). The first proband carried a 3-bp in-frame deletion in PCDH15 (5601delAAC 605514.0005) that had been identified in patients with USH1F ( 602083) and a single-basepair deletion in CDH23 (193delC 605516.0011) that had been identified in patients with USH1D. All had profound congenital nonprogressive deafness, vestibular dysfunction, and retinitis pigmentosa. They found 3 probands who carried heterozygous mutations in both CDH23 and PCDH15. (2005) carried out mutation screening for CDH23 and PCDH15 mutations in 76 probands with a diagnosis of USH1. Usher Syndrome Type ID/F, CDH23/PCDH15 Digenicįollowing the demonstration that mice heterozygous for mutations in both Cdh23 and Pcdh15 ( 605514) manifest a progressive hearing loss phenotype, Zheng et al. (2001) demonstrated that mutations in the mouse Cdh23 gene are responsible for the 'waltzer' mutation, thus establishing it as a model for USH1D. (2001) identified mutations in the CDH23 gene in homozygous or compound heterozygous state in Cuban families and a German patient with USH1D ( 605516.0001- 605516.0004). Usher syndrome, type IIC, GPR98/PDZD7 digenicīolz et al. Usher syndrome, type 2C, GPR98/PDZD7 digenic
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