Cone dystrophy associated with autoimmune polyglandular syndrome type 1

Area of Science:

• Genetics
• Ophthalmology
• Endocrinology

Background:

• Autoimmune Polyglandular Syndrome type 1 (APS1) is a rare autoimmune disorder.
• Cone dystrophy is a group of inherited retinal diseases affecting cone photoreceptors.
• Consanguineous families present unique challenges for genetic diagnosis.

Purpose of the Study:

• To investigate the association between APS1 and cone dystrophy in a large Saudi family.
• To identify the genetic basis for the co-occurrence of these conditions.

Main Methods:

• Retrospective chart review and prospective genetic testing.
• Ophthalmic examinations including visual field testing and electroretinogram (ERG).
• Whole Exome Sequencing (WES) to analyze genetic variants.

Main Results:

• Three family members were homozygous for both AIRE and PDE6C variants.
• All individuals homozygous for PDE6C variants exhibited cone dystrophy.
• All individuals homozygous for AIRE variants had APS1; two also showed reduced rod function.

Conclusions:

• The study reports the co-inheritance of APS1 and PDE6C-related cone dystrophy in a consanguineous family.
• Dual molecular diagnoses should be considered in ophthalmological practice, especially in families with unusual presentations.
• This case illustrates an unusual coincidence of two independent recessive conditions within a single family.