title: Next-generation sequencing-based molecular diagnosis of a Chinese patient cohort with autosomal recessive retinitis pigmentosa.
abstract: OBJECTIVE
  Retinitis pigmentosa (RP) is a highly heterogeneous genetic disease; therefore, an accurate molecular diagnosis is essential for appropriate disease treatment and family planning. The prevalence of RP in China had been reported at 1 in 3800, resulting in an estimated total of 340,000 Chinese RP patients. However, genetic studies of Chinese RP patients have been very limited. To date, no comprehensive molecular diagnosis has been done for Chinese RP patients. With the emergence of next-generation sequencing (NGS), comprehensive molecular diagnosis of RP is now within reach. The purpose of this study was to perform the first NGS-based comprehensive molecular diagnosis for Chinese RP patients.
  
  
  METHODS
  Thirty-one well-characterized autosomal recessive RP (arRP) families were recruited. For each family, the DNA sample from one affected member was sequenced using our custom capture panel, which includes 163 retinal disease genes. Variants were called, filtered, and annotated by our in-house automatic pipeline.
  
  
  RESULTS
  Twelve arRP families were successfully molecular diagnosed, achieving a diagnostic rate of approximately 40%. Interestingly, approximately 63% of the pathogenic mutations we identified are novel, which is higher than that observed in a similar study on European descent (45%). Moreover, the clinical diagnoses of two families were refined based on the pathogenic mutations identified in the patients.
  
  
  CONCLUSIONS
  We conclude that comprehensive molecular diagnosis can be vital for an accurate clinical diagnosis of RP. Applying this tool on patients from different ethnic groups is essential for enhancing our knowledge of the global spectrum of RP disease-causing mutations.
authors: Department of Ophthalmology, North Huashan Hospital, Fudan University, Shanghai, China.
authors: Qing
authors: Q
authors: Fu
authors: Feng
authors: F
authors: Wang
authors: Hui
authors: H
authors: Wang
authors: Fei
authors: F
authors: Xu
authors: Jacques E
authors: JE
authors: Zaneveld
authors: Huanan
authors: H
authors: Ren
authors: Vafa
authors: V
authors: Keser
authors: Irma
authors: I
authors: Lopez
authors: Han-Fang
authors: HF
authors: Tuan
authors: Jason S
authors: JS
authors: Salvo
authors: Xia
authors: X
authors: Wang
authors: Li
authors: L
authors: Zhao
authors: Keqing
authors: K
authors: Wang
authors: Yumei
authors: Y
authors: Li
authors: Robert K
authors: RK
authors: Koenekoop
authors: Rui
authors: R
authors: Chen
authors: Ruifang
authors: R
authors: Sui
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D002648:Child; D002681:China; D015331:Cohort Studies; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009154:Mutation; D012174:Retinitis Pigmentosa / Q000175:diagnosis* / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods*; D055815:Young Adult
keywords: Chinese population; molecular diagnosis; next-generation sequencing; retinitis pigmentosa
references: Eur J Hum Genet. 2013 Mar;21(3):274-80
references: 22968130
references: Genome Res. 2010 Sep;20(9):1297-303
references: 20644199
references: Hum Mutat. 2011 Aug;32(8):894-9
references: 21520341
references: Am J Ophthalmol. 2005 May;139(5):894-9
references: 15860296
references: Orphanet J Rare Dis. 2006 Oct 11;1:40
references: 17032466
references: J Med Genet. 2005 Jul;42(7):e47
references: 15994872
references: Orphanet J Rare Dis. 2012 Jan 25;7:8
references: 22277662
references: Mol Vis. 2008;14:2067-75
references: 19023448
references: Hum Mutat. 2003 Jun;21(6):577-81
references: 12754702
references: J Med Genet. 2012 May;49(5):322-6
references: 22581970
references: Bioinformatics. 2009 Jul 15;25(14):1754-60
references: 19451168
references: Am J Hum Genet. 2004 May;74(5):817-26
references: 15042513
references: PLoS One. 2012;7(9):e45464
references: 23029027
references: Methods Mol Biol. 2000;132:365-86
references: 10547847
references: PLoS One. 2012;7(2):e31036
references: 22363543
references: Nucleic Acids Res. 2003 Jul 1;31(13):3812-4
references: 12824425
references: Nature. 2010 Oct 28;467(7319):1061-73
references: 20981092
references: Biochem Biophys Res Commun. 2010 Oct 8;401(1):42-7
references: 20832389
references: J Med Genet. 1987 Oct;24(10):584-8
references: 3500313
references: J Med Genet. 2012 Jan;49(1):27-36
references: 22135276
references: Br J Ophthalmol. 2001 Sep;85(9):1046-8
references: 11520753
references: Mol Vis. 2012;18:744-50
references: 22509104
references: Mol Vis. 2011;17:1537-52
references: 21686329
references: Nucleic Acids Res. 2010 Sep;38(16):e164
references: 20601685
references: Mol Vis. 2012;18:1478-83
references: 22736939
references: Mol Vis. 2011;17:2706-16
references: 22065924
references: Nucleic Acids Res. 2010 Jun;38(10):e116
references: 20164091
references: Lancet. 2006 Nov 18;368(9549):1795-809
references: 17113430
references: PLoS One. 2012;7(5):e33673
references: 22693542
references: Am J Hum Genet. 2007 Sep;81(3):559-75
references: 17701901
references: Invest Ophthalmol Vis Sci. 2006 Jul;47(7):3052-64
references: 16799052
references: Mol Vis. 2010 Dec 03;16:2550-8
references: 21151602
references: Hum Mutat. 2012 Jun;33(6):963-72
references: 22334370
references: BMC Bioinformatics. 2012 Jan 12;13:8
references: 22239737
references: Mol Vis. 2009 Nov 24;15:2464-9
references: 19956407
references: Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9370-4
references: 1833777
references: Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6481-5
references: 1862076
references: Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3249-53
references: 7724547
references: Genet Test. 2000;4(1):1-7
references: 10794354