Isolated rod-cone dystrophy in homozygous IFT140 missense allele p.Tyr923Asp

IFT140 encodes a core intraflagellar transport protein essential for ciliary function. While biallelic IFT140 variants typically cause syndromic ciliopathies such as Mainzer-Saldino syndrome, isolated retinal phenotypes are increasingly recognized. We describe two affected siblings from a consanguineous Pakistani family with lifelong nyctalopia and progressive peripheral field loss associated with a homozygous IFT140 missense variant, c.2767T > G (p.Tyr923Asp) (NM_014714.3).

Detailed ophthalmic evaluation included multimodal retinal imaging, electrodiagnostics, and microperimetry. Systemic screening and segregation analysis were undertaken.

Both brothers exhibited classical rod-cone dystrophy with parafoveal hyperautofluorescent rings and parafoveal ellipsoid zone loss on OCT. Electroretinography confirmed reduced dark and light-adapted responses. Systemic evaluation at diagnosis and eight years later, including renal, skeletal, and auditory assessments, was normal. Segregation testing demonstrated autosomal-recessive inheritance, with both parents heterozygous and the unaffected sister a non-carrier. The variant, absent from gnomAD, now meets Association for Clinical Genomic Science (ACGS) criteria for Likely Pathogenic classification.

Homozygosity for the likely pathogenic IFT140 c.2767T > G (p.Tyr923Asp) causes isolated rod-cone dystrophy without systemic involvement. This report expands the IFT140 phenotypic spectrum, emphasizing the importance of precise molecular diagnosis for variant reclassification, genetic counseling, and gene therapy eligibility.