Mutations in the ciliary transport gene IFT140 cause syndromic congenital retinal dystrophy

J AAPOS. 2024 Oct;28(5):104007. doi: 10.1016/j.jaapos.2024.104007. Epub 2024 Sep 19.

Abstract

Early-onset, severe retinal dystrophy can be isolated or syndromic, presenting as part of an underlying systemic disease. Mainzer-Saldino syndrome, a rare systemic ciliopathy characterized by skeletal and renal disease, is caused by recessive mutations in the intraflagellar transport 140 chlamydomonas homologue (IFT140) gene. We present a series of 13 cases of early-onset retinal dysfunction with confirmed IFT140 mutations from 8 unrelated Saudi families belonging to 3 well-known tribes. All carried the same homozygous missense IFT140 mutation (c.1990G>A; p.Glu664Lys) except for a single family, which included 4 affected subjects, 3 of whom were aborted fetuses, with compound heterozygous pathogenic IFT140 variants (c.1525-1G>A and c.1990G>A; p.Glu664Lys). Severe retinal dystrophy was present in all living subjects, phenotypically apparent as hyperopia, nystagmus, nyctalopia, poor vision and nonrecordable full-field electroretinography. All affected individuals had skeletal abnormalities, and neurological abnormalities were common, but there was no evidence of chronic renal failure.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Carrier Proteins* / genetics
  • Cerebellar Ataxia
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Electroretinography*
  • Female
  • Humans
  • Infant
  • Kidney Diseases, Cystic / congenital
  • Kidney Diseases, Cystic / genetics
  • Male
  • Mutation, Missense / genetics
  • Pedigree*
  • Retinal Dystrophies* / diagnosis
  • Retinal Dystrophies* / genetics
  • Retinitis Pigmentosa

Substances

  • IFT140 protein, human
  • Carrier Proteins

Supplementary concepts

  • Mainzer-Saldino Disease