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Tengyang Sun, Ke Xu, Xiaohui Zhang, Yang Li; Comprehensive Molecular Screening in a Large Chinese Cohort with Usher Syndrome. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2342.
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© ARVO (1962-2015); The Authors (2016-present)
Usher syndrome (USH) is a group of autosomal recessive disorders causing deaf-blindness. The molecular diagnosis for USH is very challenging due to its highly clinical and genetic heterogeneities. The objective of this study was to determine mutation spectrum in a cohort of Chinese patients with USH and describe the clinical features of the patients with mutations.
A total of 119 probands clinical diagnosed with USH were recruited for genetic analysis; these includes 20 USH type1 patients and 99 USH type2 patients. All probands underwent ophthalmic examinations. A combination of molecular screening methods, which include targeted next-generation sequencing, Sanger-DNA sequencing, and multiplex ligation probe amplification assay, were used to detect mutations.
We found bi-allelic mutations in 92 unrelated patients (77.3%), mono-allelic mutations in 5 patients (4.2%), one semi-mutation in 1 patients (0.8%), and no mutation in 21 affected individuals, giving an overall mutation detection rate 82.4%(Fig. 1A). Overall 132 distinct disease-causing variants involving 7 USH genes and 5 other retinal degeneration genes were identified and 77 were novel. Mutations of MYOA7 were responsible for 60% of USH type1 families, followed by PCDH15 (25%) and USH1C (10%)(Fig. 1B). Mutations of USH2A accounted for 67.7% of USH type2 families(Fig. 1C) and mutation c.8559-2A>G was the most frequent mutation accounting for 19.1% of the identified USH2A alleles. No mutations were found in CIB2, DFNB31, and CLRN1. Remarkably, two unrelated patients were found harboring the mutations of two genes, one RP-causing gene and one USH gene(Fig. 2).
Our results further confirmed that the mutations spectrum for each USH genes in Chinese patients is different from the one of other populations. The formation of the mutation profile for a Chinese population will enable precisely genetic diagnosis for USH patients in the future.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
Summary of the proportion of patients with mutations of involving genes in this study. A, The proportion in the total patients. B, The proportion in the USH1 patients. C, The proportion in the USH2 patients.
Pedigrees, fundus photos and pure tone audiometry (PTA) results of the patients in family 019691 and 019791. A, Pedigrees and segregation analysis of family 019791 and 019691. B-C, Ocular findings and PTA results of proband 019791 and her brother. C, Fundus photos of proband 019691.
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