PNPLA6 disorders: what's in a name?

Area of Science:

• Genetics
• Neurology
• Ophthalmology

Background:

• Patatin-like phospholipase domain containing 6 (PNPLA6) gene variants are linked to diverse neurological disorders.
• These disorders manifest with gait disturbance, visual impairment, hypopituitarism, and hair anomalies.
• This review synthesizes clinical, cellular, and biochemical data for five PNPLA6-related diseases.

Purpose of the Study:

• To review the clinical, cellular, and biochemical features of PNPLA6-related diseases.
• To identify future research directions for understanding these rare neurological conditions.

Main Methods:

• Comprehensive literature review of clinical reports on patients with PNPLA6 variants.
• Summary of in vitro and in vivo models studying the PNPLA6-encoded protein, Neuropathy Target Esterase (NTE).

Main Results:

• Biallelic pathogenic PNPLA6 variants cause five distinct neurological disorders.
• PNPLA6 encodes NTE, crucial for phospholipid homeostasis and neural trafficking.
• Ocular findings include a chorioretinal dystrophy resembling choroideremia and Leber congenital amaurosis.

Conclusions:

• Clinicians should recognize the choroideremia-like ocular presentation in patients with PNPLA6 variants, alongside other symptoms.
• Further research is needed to correlate genotype with retinopathy to enhance diagnosis and prognosis.