High Myopia

Importance of comprehensive and up-to-date gene-phenotype data

History

  • Family from Lebanon
    originally seen in clinic in 1977
  • Parents reported as cousins
    homozygous variation up-ranked by our algorithms
  • Three brothers with cataracts and early onset retinal detachment
    carried a tentative diagnosis of “atypical Stickler syndrome”

ACE Clinical Exome Test was performed on two of the affected siblings

 

Case Study 1

Results

  • Novel, homozygous variant in LEPREL1 was identified.
  • One case report in the literature of another family with early-onset cataracts and vitreo-retinal degeneration due to a different homozygous variant in LEPREL1.
  • This case represents only the second ever described case of LEPREL1 variants in association with this phenotype.
  • There currently is no clinical genetic testing available for LEPREL1.
  • Demonstrates the importance of our comprehensive, up-to-date gene-phenotype information for interpretation.

Retinitis Pigmentosa

Prior panel test was negative but ACE Exome Test was positive

History

  • Identical twin brothers
    no family history
  • Infantile onset rod-cone demonstrated retinitis pigmentosa
  • High myopia
  • Prior testing of the proband with a 13 gene autosomal recessive retinitis pigmentosa panel was negative

ACE Clinical Exome Test was performed on one of the identical twins

Case Study 2Results

  • The ACE Clinical Exome Test identified a frameshift variant (p.Glu809Glyfs*25) inRPGR within exon ORF15, where most other pathogenic RPGR variants are found. The genetic location of this variant is not well covered by a standard exome platform and would have been missed with standard exome sequencing. The ACE Exome Clinical Exome Test provides high levels of gene finishing for biomedically important genes, improving sensitivity to detect variants.
  • The ACE Clinical Exome Test data is interpreted and can be reinterpreted in an up-to-date fashion as compared to gene panel tests that may become outdated as new genes are discovered.