AI Article Synopsis

  • Genome sequencing at base pair resolution reveals genetic causes of atypical hereditary sensory and autonomic neuropathy, epilepsy, and developmental delays in a patient.
  • The patient was found to have rare variants in the RETREG1 gene linked to hereditary sensory and autonomic neuropathy and a de novo mutation in the DNM1L gene associated with dominant forms of encephalopathy and epilepsy.
  • This study highlights how comprehensive genome sequencing can improve diagnosis accuracy for complex genetic disorders.

Article Abstract

Background: Profiling the entire genome at base pair resolution in a single test offers novel insights into disease by means of dissection of genetic contributors to phenotypic features.

Methods: We performed genome sequencing for a patient who presented with atypical hereditary sensory and autonomic neuropathy, severe epileptic encephalopathy, global developmental delay, and growth hormone deficiency.

Results: Assessment of the variants detected by mapped sequencing reads followed by Sanger confirmation revealed that the proband is a compound heterozygote for rare variants within RETREG1 (FAM134B), a gene associated with a recessive form of hereditary sensory and autonomic neuropathy, but not with epileptic encephalopathy or global developmental delay. Further analysis of the data also revealed a heterozygous missense variant in DNM1L, a gene previously implicated in an autosomal dominant encephalopathy, epilepsy, and global developmental delay and confirmed by Sanger sequencing to be a de novo variant not present in parental genomes.

Conclusions: Our findings emphasize the importance of genome-wide sequencing in patients with a well-characterized genetic disease with atypical presentation. This approach reduces the potential for misdiagnoses.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785439PMC
http://dx.doi.org/10.1002/mgg3.961DOI Listing

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