TY - JOUR
T1 - The current status of molecular diagnosis of inherited retinal dystrophies
AU - Chiang, John Pei Wen
AU - Trzupek, Karmen
N1 - Publisher Copyright:
Copyright © 2015 Wolters Kluwer Health, Inc.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - Purpose of review We are witnessing lightning-fast advances in the molecular diagnosis of inherited retinal dystrophies, mainly due to the widespread use of next-generation sequencing technologies. The purpose of this review is to highlight the breadth of findings from this in-depth testing approach, and to propose changes to our traditional testing and diagnostic paradigms. Lessons learned from modern molecular testing suggest that the previous concept of inherited retinal dystrophies as a group of 'single gene diseases' may require a significant update. Recent findings All of the known retinal dystrophies genes can now be sequenced. In many cases, this nonhypothesis driven testing strategy is uncovering mutations in unsuspected genes, generating data that challenges established concepts of genetic mechanisms and provides insights regarding genes previously thought to be exclusively related to syndromic disease. Recent advances in testing have improved not only the breadth, but also the depth of genetic data. For example, deep intronic sequencing has uncovered many novel intronic mutations/variations in the ABCA4 gene. Summary Currently, in approximately 50-60% of patients with nonsyndromic retinal dystrophy, the disease mechanism can be identified. The presence of pathogenic alleles in more than one gene is not uncommon. Retinal dystrophy, with relatively defined clinical presentations and a large but limited number of genes involved, is becoming a model for the next-generation study of molecular disease mechanisms.
AB - Purpose of review We are witnessing lightning-fast advances in the molecular diagnosis of inherited retinal dystrophies, mainly due to the widespread use of next-generation sequencing technologies. The purpose of this review is to highlight the breadth of findings from this in-depth testing approach, and to propose changes to our traditional testing and diagnostic paradigms. Lessons learned from modern molecular testing suggest that the previous concept of inherited retinal dystrophies as a group of 'single gene diseases' may require a significant update. Recent findings All of the known retinal dystrophies genes can now be sequenced. In many cases, this nonhypothesis driven testing strategy is uncovering mutations in unsuspected genes, generating data that challenges established concepts of genetic mechanisms and provides insights regarding genes previously thought to be exclusively related to syndromic disease. Recent advances in testing have improved not only the breadth, but also the depth of genetic data. For example, deep intronic sequencing has uncovered many novel intronic mutations/variations in the ABCA4 gene. Summary Currently, in approximately 50-60% of patients with nonsyndromic retinal dystrophy, the disease mechanism can be identified. The presence of pathogenic alleles in more than one gene is not uncommon. Retinal dystrophy, with relatively defined clinical presentations and a large but limited number of genes involved, is becoming a model for the next-generation study of molecular disease mechanisms.
KW - Genetic testing
KW - Molecular diagnosis
KW - Mutation
KW - Retinal dystrophy
KW - Retinitis pigmentosa
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U2 - 10.1097/ICU.0000000000000185
DO - 10.1097/ICU.0000000000000185
M3 - Review article
C2 - 26214332
AN - SCOPUS:84942508621
SN - 1040-8738
VL - 26
SP - 346
EP - 351
JO - Current opinion in ophthalmology
JF - Current opinion in ophthalmology
IS - 5
ER -