Genotype-phenotype correlation in a novel ABHD12 mutation underlying PHARC syndrome

Area of Science:

• Genetics
• Neuroscience
• Ophthalmology

Background:

• PHARC syndrome is a rare, genetically heterogeneous neurodegenerative disorder.
• Characterized by demyelinating polyneuropathy, hearing loss, cerebellar ataxia, retinitis pigmentosa, and early-onset cataracts.
• Often misdiagnosed as Charcot-Marie-Tooth disease or Refsum disease due to overlapping clinical features.

Observation:

• Two siblings with PHARC syndrome were analyzed.
• Next-generation sequencing identified a novel homozygous point mutation (c.784C>T, p.Arg262*) in the ABHD12 gene in both siblings.
• Clinical evaluation included history, examination, nerve conduction studies (NCS), brain imaging, and optical coherence tomography.

Findings:

• The identified ABHD12 mutation correlated with PHARC syndrome symptoms in both siblings.
• Symptoms included bilateral hearing loss, cataracts, cerebellar ataxia, and demyelinating neuropathy.
• Retinitis pigmentosa was present in one sibling.

Implications:

• Highlights the importance of molecular genetic testing for PHARC syndrome diagnosis.
• Emphasizes the need for an interdisciplinary approach to differentiate PHARC syndrome from similar neurological disorders.
• Contributes to understanding genotype-phenotype correlations in PHARC syndrome.