A novel pathogenic variant in LCAT causing FLD. A case report

Area of Science:

• Genetics
• Biochemistry
• Ophthalmology

Background:

• Familial lecithin-cholesterol acyltransferase deficiency (FLD) and Fish-eye disease (FED) are rare, autosomal recessive genetic disorders.
• Both conditions result from partial or complete lecithin-cholesterol acyltransferase (LCAT) deficiency.
• Clinical manifestations include low HDL cholesterol, corneal opacity, and, in FLD, kidney damage.

Observation:

• A 63-year-old male presented with dyslipidemia, chronic kidney disease, and corneal disorders.
• Genetic counseling was sought due to decreased visual acuity from corneal opacity, prompting investigation for LCAT deficiency.
• Massive DNA sequencing utilized a multigene panel for lipid metabolism disorders.

Findings:

• Two likely pathogenic missense variants (c.491 G>A and c.496 G>A) in the LCAT gene were identified.
• These variants result in amino acid substitutions, altering the protein sequence and 3D structure.
• Genetic confirmation was achieved through Sanger sequencing.

Implications:

• Accurate diagnosis of FLD and FED is crucial for patient management and access to therapies.
• Understanding the genetic basis of these rare diseases aids in differential diagnosis.
• This case contributes to the literature on FLD and FED, enhancing knowledge of their genetic and clinical profiles.