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Macular Dystrophy Panel

The Macular Dystrophy Panel is a comprehensive next-generation sequencing (NGS) panel that can be used to confirm a clinical diagnosis of macular dystrophy or identify at-risk individuals.

Macular dystrophies are a group of heterogeneous disorders affecting the macula, which is the central area of the retina. The macula is involved in central vision, and individuals with macular dystrophy typically have reduced visual acuity, and difficulties with tasks like driving or recognizing faces. The age of onset, rate of progression, and severity of vision loss varies based on the specific type of macular dystrophy.

Included Disorders

This panel includes genes associated with:

  • Juvenile macular degeneration
  • Stargardt disease
  • Retinitis pigmentosa
  • Senior-Loken syndrome
  • Vitelliform macular dystrophy
  • Cone-rod dystrophy
  • Retinoschisis
  • Retinitis punctata albescens
  • Leber congenital amaurosis
  • Newfoundland Rod-cone dystrophy
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    Prevalence

    The prevalence of macular dystrophy varies by disorder, although the prevalence of Stargardt disease, one of the most common macular dystrophies, is 1 in 8,000 individuals (Molday and Zhang, 2010).

    Inheritance and Penetrance

    Macular dystrophy may be inherited in autosomal dominant, autosomal recessive, or X-linked fashions, and is typically fully penetrant.

    Clinical Sensitivity

    Clinical sensitivity varies based on patient’s phenotype. Disease causing variants can be identified in approximately 80% of Stargardt disease cases and >95% of Best vitelliform macular dystrophy cases with a positive family history (Shroyer et al, 2001; Kramer et al, 2000). The Macular Dystrophy Panel includes all of the common genetic causes related to these diseases.

    Methodology and Analytical Sensitivity

    Next-generation sequencing technology is used to test clinically relevant portions of each gene, including coding exons, adjacent flanking bases, and selected introns/noncoding variants. Pathogenic and likely pathogenic variants are confirmed by orthogonal methods. Copy number variants, including intragenic deletions and duplications are detected to a resolution of a single exon. To request analysis of a specific single exon copy number variant, please contact our Client Services team prior to ordering. Analytical sensitivity and specificity of the assay is >99%.

    Indications for Testing

    • Confirmation of a clinical diagnosis
    • Risk assessment for asymptomatic family members of proband with molecular diagnosis of macular dystrophy

    Included genes (21)

    ABCA4 CERKL EFEMP1 IMPG1 RAX2 RDH5 RPGR
    BEST1 CNGB3 ELOVL4 PROM1 RBP4 RLBP1 RS1
    CDH3 CRB1 FBLN5 PRPH2 RDH12 RP1L1 TIMP3

     

    Additions to the Macular Dystrophy Panel

    Emerging evidence genes can also be added to the Macular Dystrophy Panel. These genes do not have a clear association with macular dystrophy, but emerging evidence suggests that they may play a role in disease pathogenesis:

    Emerging Evidence Genes (3)

    FSCN2 GUCA1B PRDM13

     

    References

    1. Krämer F, White K, Pauleikhoff D, et al. Mutations in the VMD2 gene are associated with juvenile-onset vitelliform macular dystrophy (Best disease) and adult vitelliform macular dystrophy but not age-related macular degeneration. Eur J Hum Genet. 2000;8(4):286-92.
    2. Molday RS, Zhang K. Defective lipid transport and biosynthesis in recessive and dominant Stargardt macular degeneration. Prog Lipid Res. 2010;49(4):476-92.
    3. Shroyer NF, Lewis RA, Yatsenko AN, Wensel TG, Lupski JR. Cosegregation and functional analysis of mutant ABCR (ABCA4) alleles in families that manifest both Stargardt disease and age-related macular degeneration. Hum Mol Genet. 2001;10(23):2671-8.