PanelSure - NGS >> Ent Panels >> Eye Disorders: Comprehensive Sequencing Panel

Eye Disorders: Comprehensive Sequencing Panel

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Condition Description Indications
Detection Specimen Requirements

 

Condition Description

The Eye Disorder Comprehensive Sequencing Panel is an analysis of almost all clinically relevant genes identified as causing syndromic and non- syndromic inherited retinal and choroidal dystrophies, as well as ocular developmental disorders. There is a wide range of genetic and phenotypic heterogeneity in retinal and choroidal disorders making accurate clinical diagnosis difficult especially during early phases of the disease onset.

Retinal disorders can be congenital and present at birth (as in Leber congenital amaurosis), present in early childhood (as in early onset retinitis pigmentosa), or present in mid life (as in pattern dystrophy). The clinical features of retinal disorders include vision loss, vision distortion, loss of peripheral vision, and night blindness. Fundus exam findings can range from almost normal appearance of the retina (as in Leber congenital amaurosis) to pale optic nerve, narrowed arterioles, bone spicules, photo receptor loss, retinal pigment epithelial changes, and chorioretinal atrophy. The fundus appearance in the end stage of many retinal disorders, such as pattern dystrophy and cone-rod dystrophy, may be similar to that of macular dystrophy or chorioretinal atrophy. Electroretinogram (ERG) findings can range from non-recordable ERG to loss of rod or cone responses and be non-specific. Rarely, characteristic findings in ERG as in congenital stationary night blindness may help in arriving at a more accurate diagnosis. Detailed history and clinical examination, optical coherence tomography (OCT), pattern of visual field loss and ERG may help narrow the selection of disease causing genes or groups of genes.

Genes

ABCA4, ABHD12, ADAM9, ADGRV1, AHI1, AIPL1, ALMS1, ARL13B, ARL6, ATP13A2, B3GLCT, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, BCOR, BEST1, BMP4, C10orf11, C1QTNF5, C2orf71, C5orf42, C8orf37, CA4, CABP4, CACNA1F, CACNA2D4, CC2D2A, CDH23, CDH3, CDHR1, CEP290, CEP41, CERKL, CHM, CIB2, CLN3, CLN5, CLN6, CLN8, CLRN1, CNGA1, CNGA3, CNGB1, CNGB3, CNNM4, COL11A1, COL11A2, COL2A1, COL4A1, COL9A1, COL9A2, CRB1, CRX, CTSD, CYP1B1, CYP27A1, CYP4V2, DHDDS, EFEMP1, ELOVL4, EYS, FAM161A, FLVCR1, FOXC1, FOXE3, FRAS1, FREM1, FREM2, FSCN2, FZD4, GNAT1, GNAT2, GPR143, GPR179, GRIP1, GRM6, GRN, GUCA1A, GUCA1B, GUCY2D, HARS, HCCS, IDH3B, IMPDH1, IMPG2, INVS, IQCB1, KCNJ13, KCNV2, KCTD7, KIF7, KLHL7, LCA5, LRAT, LRIT3, LRP5, LZTFL1, MAK, MERTK, MFN2, MFRP, MFSD8, MKKS, MKS1, MTTP, MYO7A, MYOC, NDP, NPHP1, NPHP3, NPHP4, NR2E3, NRL, NYX, OAT, OCA2, OFD1, OPA1, OPA3, OTX2, PAX6, PCDH15, PDE6A, PDE6B, PDE6C, PDE6G, PDE6H, PEX7, PHYH, PITPNM3, PITX2, PITX3, PLA2G5, PPT1, PRCD, PROM1, PRPF3, PRPF31, PRPF6, PRPF8, PRPH2, RAX2, RBP3, RBP4, RD3, RDH12, RDH5, RGR, RGS9, RGS9BP, RHO, RIMS1, RLBP1, ROM1, RP1, RP2, RP9, RPE65, RPGR, RPGRIP1, RPGRIP1L, RS1, SAG, SDCCAG8, SEMA4A, SLC24A1, SLC24A5, SLC45A2, SMOC1, SNRNP200, SOX2, SPATA7, STRA6, TCTN1, TCTN2, TCTN3, TIMM8A, TIMP3, TMEM126A, TMEM216, TMEM237, TMEM67, TOPORS, TPP1, TRIM32, TRPM1, TSPAN12, TTC21B, TTC8, TULP1, TYR, TYRP1, UNC119, USH1C, USH1G, USH2A, VAX1, VCAN, VSX2, WDPCP, WFS1, WHRN, WT1, ZNF423, ZNF513

Indications

This test is indicated for:

Confirmation of a clinical diagnosis of a syndromic and/or non-syndromic retinal and optic nerve disorders.

Carrier testing in adults with a family history of a syndromic and/or non-syndromic retinal and optic nerve disorders.

Methodology

Next Generation Sequencing: In-solution hybridization of all coding exons is performed on the patient's genomic DNA. Although some deep intronic regions may also be analyzed, this assay is not meant to interrogate most promoter regions, deep intronic regions, or other regulatory elements, and does not detect single or multi-exon deletions or duplications. Direct sequencing of the captured regions is performed using next generation sequencing. The patient's gene sequences are then compared to a standard reference sequence. Potentially causative variants and areas of low coverage are Sanger-sequenced. Sequence variations are classified as pathogenic, likely pathogenic, benign, likely benign, or variants of unknown significance. Variants of unknown significance may require further studies of the patient and/or family members.

Detection

Clinical Sensitivity: Unknown. Pathogenic variants in the promoter region, some pathogenic variants in the introns and other regulatory element pathogenic variants cannot be detected by this analysis. Large deletions will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient's clinical and/or biochemical phenotype.

Analytical Sensitivity:~99%.

Seven targeted mtDNA pathogenic variants: Leber Hereditary Optic Neuropathy(LHON)

Four pathogenic variants (that account for 90% of cases of LHON) will be detected by this assay: 11778G>A, 3460G>A, 14459G>A, &14484T>C.

Retinitis Pigmentosa and Ataxia(NARP)

Two pathogenic variants (that account for 50% of cases of NARP) will be detected by this assay: 8993T>G and 8993T>C.

Chronic Progressive External Ophthalmoplegia (CPEO)

One pathogenic variant  will be detected by this assay:3243A>G.

Note: These mtDNA variants will be detected down to approximately 15-20% heteroplasmy.

Specimen Requirements

Submit only 1 of the following specimen types

Type: EDTA Whole Blood; Infants (2 years): 3-5 ml; Older Children & Adults: 5-10 ml.

Type: Isolated DNA: In microtainer: (20-30 ug high Quality Genomic DNA, shipped at 2-4 oC). Isolation using the QiagenTM  Puregene kit for DNA extraction is recommended.

Specimen Collection and Shipping: Refrigerate until time of shipment in 100 ng/ul of TE buffer. Ship sample at room temperature with overnight delivery.

ABCA4, ABHD12, ADAM9, ADGRV1, AHI1, AIPL1, ALMS1, ARL13B, ARL6, ATP13A2, B3GLCT, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, BCOR, BEST1, BMP4, C10orf11, C1QTNF5, C2orf71, C5orf42, C8orf37, CA4, CABP4, CACNA1F, CACNA2D4, CC2D2A, CDH23, CDH3, CDHR1, CEP290, CEP41, CERKL, CHM, CIB2, CLN3, CLN5, CLN6, CLN8, CLRN1, CNGA1, CNGA3, CNGB1, CNGB3, CNNM4, COL11A1, COL11A2, COL2A1, COL4A1, COL9A1, COL9A2, CRB1, CRX, CTSD, CYP1B1, CYP27A1, CYP4V2, DHDDS, EFEMP1, ELOVL4, EYS, FAM161A, FLVCR1, FOXC1, FOXE3, FRAS1, FREM1, FREM2, FSCN2, FZD4, GNAT1, GNAT2, GPR143, GPR179, GRIP1, GRM6, GRN, GUCA1A, GUCA1B, GUCY2D, HARS, HCCS, IDH3B, IMPDH1, IMPG2, INVS, IQCB1, KCNJ13, KCNV2, KCTD7, KIF7, KLHL7, LCA5, LRAT, LRIT3, LRP5, LZTFL1, MAK, MERTK, MFN2, MFRP, MFSD8, MKKS, MKS1, MTTP, MYO7A, MYOC, NDP, NPHP1, NPHP3, NPHP4, NR2E3, NRL, NYX, OAT, OCA2, OFD1, OPA1, OPA3, OTX2, PAX6, PCDH15, PDE6A, PDE6B, PDE6C, PDE6G, PDE6H, PEX7, PHYH, PITPNM3, PITX2, PITX3, PLA2G5, PPT1, PRCD, PROM1, PRPF3, PRPF31, PRPF6, PRPF8, PRPH2, RAX2, RBP3, RBP4, RD3, RDH12, RDH5, RGR, RGS9, RGS9BP, RHO, RIMS1, RLBP1, ROM1, RP1, RP2, RP9, RPE65, RPGR, RPGRIP1, RPGRIP1L, RS1, SAG, SDCCAG8, SEMA4A, SLC24A1, SLC24A5, SLC45A2, SMOC1, SNRNP200, SOX2, SPATA7, STRA6, TCTN1, TCTN2, TCTN3, TIMM8A, TIMP3, TMEM126A, TMEM216, TMEM237, TMEM67, TOPORS, TPP1, TRIM32, TRPM1, TSPAN12, TTC21B, TTC8, TULP1, TYR, TYRP1, UNC119, USH1C, USH1G, USH2A, VAX1, VCAN, VSX2, WDPCP, WFS1, WHRN, WT1, ZNF423, ZNF513