Clinical and molecular findings of FRMD7 related congenital nystagmus as adifferential diagnosis of ocular albinism

Ophthalmic Genet. 2019 Apr;40(2):161-164. doi: 10.1080/13816810.2019.1592201. Epub 2019 Apr 3.

Abstract

Background: Congenital nystagmus is one of the most common neuro-ophthalmological disorders. X chromosome-linked forms are associated with pathogenic variants of the GPR143 and FRMD7 genes.

Materials and methods: Patients' DNA was analyzed using a next-generation sequencing (NGS) panel of genes involved in albinism and related pathologies (TYR, OCA2, TYRP1, SLC45A2, SLC24A5, C10ORF11, GPR143, SLC38A8, HPS 1 to 10, LYST, MITF, FRMD7) Results: We report a 4 generation family with 5 affected members initially referred for molecular diagnosis of ocular albinism. A missense variant of FRMD7 was found in 3 affected cases and one female carrier. We show that the disease in the affected girl is due to skewed inactivation of the X chromosome.

Conclusions: By compiling all the published cases we discuss the variable penetrance among females due to different types of mutation and to X-inactivation.

Keywords: Congenital nystagmus; albinism; molecular genetics; next-generation sequencing.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albinism, Ocular / diagnosis
  • Albinism, Ocular / genetics*
  • Child
  • Cytoskeletal Proteins / genetics*
  • Diagnosis, Differential
  • Female
  • Genetic Diseases, X-Linked / genetics*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infant
  • Male
  • Membrane Proteins / genetics*
  • Mutation, Missense*
  • Nystagmus, Congenital / diagnosis
  • Nystagmus, Congenital / genetics*
  • Pedigree
  • Slit Lamp Microscopy
  • Tomography, Optical Coherence
  • X Chromosome Inactivation / genetics*

Substances

  • Cytoskeletal Proteins
  • FRMD7 protein, human
  • Membrane Proteins