Skip to main content

Table 6 Patients with unsolved genotype and unlikely disease causing mutations

From: Development and application of a next-generation-sequencing (NGS) approach to detect known and novel gene defects underlying retinal diseases

Index Phenotype Pre-screening Gene Mutation Allele State Read reference NGS Read variant NGS Mutation verified by Sanger and co-segregation Comment
CIC03282,
F1388
Stargardt ABCA4 microarray ABCA4 c.1268A > G
p.H423R
het 77 61 yes but reported as polymorphism
[71]
     c.6764G > T
p.S2255I
no additional variants in lower covered exons
het 2 7 yes but reported as polymorphism
[72]
    CFH c.3482C > A
p.P1161Q
het 77 52 yes conserved, probably damaging
     c.1204C > T
p.H402Y
het 94 87 yes AMD
CIC01269, F761 adRP - RP1L1 c.5959C > T
p.Q1987X
het 145 150 yes, did not co-segregate pass to whole exome sequencing
CIC01312,
F795
adCD with post-receptoral defects RHO, PDE6B,
GNAT1 adRP chip
CUBN c.127C > T
p.R43X
het 139 102 yes, did not co-segregate pass to whole exome sequencing
    CUBN c.9340G > A
p.G3114S
het 61 44 yes, did not co-segregate  
    GUCY2D c.1499C > T
p.P500L
het 41 34 yes, did not co-segregate  
    TRPM1 c.3904T > C
p.C1302R
het 102 99 yes, did not co-segregate  
CIC03225,
F1362
arRP consang. arRP chip PROM1 c.314A > G
p.Y105C
het 120 115 yes, but no additional mutation no homo, no compound hets, pass to whole exome sequencing
    GUCY2D c.2917G > A
p.V973L
het 6 2 false positive, not found by Sanger  
    DSCAML1 c.592C > T
p.R198C
het 70 81 yes, but no additional mutation  
    TBC1D24 c.641G > A
p.R214H
het 27 12 yes, but no additional mutation  
    TMEM67 c.1700A > G
p.Y567C
het 80 58 yes, but no additional mutation  
CIC04757
F2364
Index and affected sister early onset arCD, macro-cephaly and mental retardation in affected sister consang. - IMPG2 c.3439C > T
p.P1147S
homo 0 140 no Polyphen and Sift benign, not conserved
    PKD2L1 c.1027C > T
p.R343C
het 63 68   
     c.1202T > G
p.V401G
het 25 19   appeared also het in 11 of our samples
appeared also het in affected sister but no other mutation in less covered exons
    DFNB31 c.1943C > A p.S648Y het 7 7 yes affected sister also both variants but both come from father, no other variant in lower covered region.
     c.2644C > A
p.R882S
het 27 14 yes  
    EYS c.7597A > G
p.K2533E
het 151 149 yes Affected sister does not carry this variant
    RPGRIP1 c.2417C > T
p.T806I
het 138 132 no not conserved
CIC04152, F1955 male x-linked cCSNB, has affected nephew NYX TRPM1 c.470C > T
p.S157F
het 118 130 yes, no other het mutation. x-linked inheritance and phenotype verification
  1. Index patients and respective gene defect are highlighted in bold. In some cases also family members were used for NGS.