Figure 1 Pedigree of the three Chinese families with Usher syndrome type II who had mutations in USH2A. Males and females are represented by squares and circles, respectively. The symbols for affected family member are filled. The symbols for deceased family members have a slash. The symbols for proband have an arrow. The genotype of each evaluated individual is shown below the individuals symbol and identification number. Abbreviations: Wild type (+); c.8559 2A>G (M1); p.T3936P (M2); p.R34fs (M3); p.S2828fs (M4); p.W3150X (M5)..
Identification of five novel mutations in the long isoform of the USH2A gene in Chinese families with Usher syndrome type II
Mol Vis. 2008 Nov 17; 14:2067-2075
PurposeUsher syndrome type II (USH2) is the most common form of Usher syndrome, an autosomal recessive disorder characterized by moderate to severe he.....
PurposeUsher syndrome type II (USH2) is the most common form of Usher syndrome, an autosomal recessive disorder characterized by moderate to severe hearing loss, postpuberal onset of retinitis pigmentosa (RP), and normal vestibular function. Mutations in the USH2A gene have been shown to be responsible for most cases of USH2. To further elucidate the role of USH2A in USH2, mutation screening was undertaken in three Chinese families with USH2.MethodsThree unrelated Chinese families, consisting of six patients and 10 unaffected relatives, were examined clinically, and 100 normal Chinese individuals served as controls. Genomic DNA was extracted from the venous blood of all participants. The coding region (exons 2 72), including the intron exon boundary of USH2A, was amplified by polymerase chain reaction (PCR). The PCR products amplified from the three probands were analyzed using direct sequencing to screen sequence variants. Whenever substitutions were identified in a patient, restriction fragment length polymorphism analysis, or single strand conformation polymorphism analysis was performed on all available family members and the control group.ResultsFundus examination revealed typical fundus features of RP, including narrowing of the vessels, bone speckle pigmentation, and waxy optic discs. The ERG wave amplitudes of three probands were undetectable. Audiometric tests indicated moderate to severe sensorineural hearing impairment. Vestibular function was normal. Five novel mutations (one small insertion, one small deletion, one nonsense, one missense, and one splice site) were detected in three families after sequence analysis of USH2A. Of the five mutations, four were located in exons 22 72, specific to the long isoform of USH2A.ConclusionsThe mutations found in our study broaden the spectrum of USH2A mutations. Our results further indicate that the long isoform of USH2A may harbor even more mutations of the USH2A gene.