Figure S1. the Genotype and Phenotype of Patient W29-1

Supplementary information

Supplementary information includes Figure S1, S2 and S3; TablesS1, S2, S3, S4 and S5.

Figure S1. The genotype and phenotype of patient W29-1

A. Pedigree and mutations segregating within the family; B. Sequencing chromatograms of the family; C. ERG examination of the proband.

Figure S2. The genotype and phenotype of patient W83-1

A. Pedigree and mutations segregating within the family; B. Sequencing chromatograms of the proband; C. Fundus image of the proband.

Figure S3. The genotype and phenotype of patient W196-1

A. Pedigree and mutations segregating within the family; B. Sequencing chromatograms of the proband; C. TheY218C mutation is located in a highly conserved region; D. Fundus image of the proband.

Table S1. List of 164known retinal-disease genes.

Table S2. List of 88possiblecandidate genes.

Table S3. List of 32 microRNAs.

Table S4. Phenotypic and genotypic information in ninety-nine IRD patients.

M, male; F, female; RP, retinitis pigmentosa; Usher, Usher Syndrome; LCA, Leber congenital amaurosis; CRD, cone-rod dystrophy; BCD, Bietti crystalline dystrophy; CSNB, congenital stationary night blindness; ESCS, enhanced Scone syndrome;BCVA, best corrected visual acuity; HM, hand movement; FC, fingers count, LP, light perception; NLP, no light perception; AR, autosomal recessive; AD, autosomal dominant; XL, X-linked; S, simplex;asterisk indicates the consanguineous families.

Table S5. Mutations identified in ninety-nine IRD patients.

a Mutation type: Hetero, heterozygous; Homo, homozygous; Hemi, hemizygous. bSeg, co-segregation. c Prediction of functional effects of missense mutations by using PolyPhen-2 and SIFT. ND, nonsense, frameshift or splice site mutations are not detected. d Allele frequencies: none, absent in the database; rare, less than 0.01.

References

1.Li L, Xiao XS, Li SQ, et al. Detection of Variants in 15 Genes in 87 Unrelated Chinese Patients with Leber Congenital Amaurosis. PLoS One. 2011;6.

2.Glockle N, Kohl S, Mohr J, et al. Panel-based next generation sequencing as a reliable and efficient technique to detect mutations in unselected patients with retinal dystrophies. Eur J Hum Genet. 2013.

3.Neidhardt J, Glaus E, Lorenz B, et al. Identification of novel mutations in X-linked retinitis pigmentosa families and implications for diagnostic testing. Mol Vis. 2008;14:1081-1093.

4.Morimura H, Fishman GA, Grover SA, Fulton AB, Berson EL, Dryja TP. Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or leber congenital amaurosis. Proc Natl Acad Sci U S A. 1998;95:3088-3093.

5.Abd El-Aziz MM, O'Driscoll CA, Kaye RS, et al. Identification of novel mutations in the ortholog of Drosophila eyes shut gene (EYS) causing autosomal recessive retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2010;51:4266-4272.

6.McGee TL, Seyedahmadi BJ, Sweeney MO, Dryja TP, Berson EL. Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome type II or non-syndromic retinitis pigmentosa. J Med Genet. 2010;47:499-506.

7.Jin ZB, Mandai M, Yokota T, et al. Identifying pathogenic genetic background of simplex or multiplex retinitis pigmentosa patients: a large scale mutation screening study. J Med Genet. 2008;45:465-472.

8.Li A, Jiao X, Munier FL, et al. Bietti crystalline corneoretinal dystrophy is caused by mutations in the novel gene CYP4V2. Am J Hum Genet. 2004;74:817-826.

9.Tang Z, Wang Z, Ke T, Wang QK, Liu M. Novel compound heterozygous mutations in CERKL cause autosomal recessive retinitis pigmentosa in a nonconsanguineous Chinese family. Arch Ophthalmol. 2009;127:1077-1078.

10.Jacobson SG, Kemp CM, Sung CH, Nathans J. Retinal function and rhodopsin levels in autosomal dominant retinitis pigmentosa with rhodopsin mutations. Am J Ophthalmol. 1991;112:256-271.

11.Aller E, Jaijo T, Beneyto M, et al. Identification of 14 novel mutations in the long isoform of USH2A in Spanish patients with Usher syndrome type II. J Med Genet. 2006;43:e55.

12.Dai H, Zhang X, Zhao X, et al. Identification of five novel mutations in the long isoform of the USH2A gene in Chinese families with Usher syndrome type II. Mol Vis. 2008;14:2067-2075.

13.Jin ZB, Liu XQ, Hayakawa M, Murakami A, Nao-i N. Mutational analysis of RPGR and RP2 genes in Japanese patients with retinitis pigmentosa: identification of four mutations. Mol Vis. 2006;12:1167-1174.

14.Zernant J, Schubert C, Im KM, et al. Analysis of the ABCA4 gene by next-generation sequencing. Invest Ophthalmol Vis Sci. 2011;52:8479-8487.

15.Fu Q, Wang F, Wang H, et al. Next-generation sequencing-based molecular diagnosis of a chinese patient cohort with autosomal recessive retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2013;54:4158-4166.

16.Rossi S, Testa F, Li AR, et al. Clinical and genetic features in Italian Bietti crystalline dystrophy patients. British Journal of Ophthalmology. 2013;97:174-179.

17.Li SQ, Xiao XS, Wang PF, Guo XM, Zhang QJ. Mutation spectrum and frequency of the RHO gene in 248 Chinese families with retinitis pigmentosa. Biochem Biophys Res Commun. 2010;401:42-47.

18.Xiao XS, Mai GY, Li SQ, Guo XM, Zhang QJ. Identification of CYP4V2 mutation in 21 families and overview of mutation spectrum in Bietti crystalline corneoretinal dystrophy. Biochem Biophys Res Commun. 2011;409:181-186.

19.Michaelides M, Gaillard MC, Escher P, et al. The PROM1 Mutation p. R373C Causes an Autosomal Dominant Bull's Eye Maculopathy Associated with Rod, Rod-Cone, and Macular Dystrophy. Invest Ophthalmol Vis Sci. 2010;51:4771-4780.

20.Iwanami M, Oshikawa M, Nishida T, Nakadomari S, Kato S. High prevalence of mutations in the EYS gene in Japanese patients with autosomal recessive retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2012;53:1033-1040.

21.Haider NB, Jacobson SG, Cideciyan AV, et al. Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate. Nat Genet. 2000;24:127-131.

22.Huang XF, Xiang P, Chen J, et al. Targeted exome sequencing identified novel USH2A mutations in Usher syndrome families. PLoS One. 2013;8:e63832.

23.Auslender N, Bandah D, Rizel L, et al. Four USH2A founder mutations underlie the majority of Usher syndrome type 2 cases among non-Ashkenazi Jews. Genet Test. 2008;12:289-294.

24.Ebermann I, Lopez I, Bitner-Glindzicz M, Brown C, Koenekoop RK, Bolz HJ. Deafblindness in French Canadians from Quebec: a predominant founder mutation in the USH1C gene provides the first genetic link with the Acadian population. Genome Biol. 2007;8:R47.

25.Besnard T, García-García G, Baux D, et al. Experience of targeted Usher exome sequencing as a clinical test. Mol Genet Genomic Med. 2014;2:30-43.

26.Dreyer B, Brox V, Tranebjaerg L, et al. Spectrum of USH2A mutations in Scandinavian patients with Usher syndrome type II. Hum Mutat. 2008;29:451.

27.Beryozkin A, Zelinger L, Bandah-Rozenfeld D, et al. Mutations in CRB1 are a Relatively Common Cause of Autosomal Recessive Early-Onset Retinal Degeneration in the Israeli and Palestinian Populations. Invest Ophthalmol Vis Sci. 2013;54:2068-2075.

28.Chen Y, Zhang Q, Shen T, et al. Comprehensive mutation analysis by whole-exome sequencing in 41 chinese families with leber congenital amaurosis. Invest Ophthalmol Vis Sci. 2013;54:4351-4357.

29.Paun CC, Pijl BJ, Siemiatkowska AM, et al. A novel crumbs homolog 1 mutation in a family with retinitis pigmentosa, nanophthalmos, and optic disc drusen. Mol Vis. 2012;18:2447-2453.

30.Littink KW, Pott JW, Collin RW, et al. A novel nonsense mutation in CEP290 induces exon skipping and leads to a relatively mild retinal phenotype. Invest Ophthalmol Vis Sci. 2010;51:3646-3652.

31.Passerini I, Sodi A, Giambene B, Mariottini A, Menchini U, Torricelli F. Novel mutations in of the ABCR gene in Italian patients with Stargardt disease. Eye (Lond). 2010;24:158-164.

32.Kroes HY, van Zon PH, Fransen van de Putte D, et al. DNA analysis of AHI1, NPHP1 and CYCLIN D1 in Joubert syndrome patients from the Netherlands. Eur J Med Genet. 2008;51:24-34.