A Disease-Causing FRMD7 Variant in a Chinese Family with Infantile Nystagmus

J Mol Neurosci. 2019 Mar;67(3):418-423. doi: 10.1007/s12031-018-1245-5. Epub 2019 Jan 8.

Abstract

In this report, we described a large Han-Chinese family which presents with various phenotypes from unaffected to manifested nystagmus in females. Infantile nystagmus (IN) is characterized by bilateral, involuntary, and periodic eyeball oscillation, occurring at birth or within the first 6 months. The most common inheritance pattern of IN is an X-linked form with incomplete penetrance among females, and the FERM domain containing 7 gene (FRMD7) is a main disease-causing gene. A combination of exome sequencing and Sanger sequencing, as well as detailed clinical examinations were performed on the Chinese IN family. An FRMD7 c.47T>C (p.Phe16Ser) variant was proposed as the disease-causing variant. Incomplete penetrance was found in females with the FRMD7 c.47T>C variant, and hemizygous male affected subjects presented more severe manifestations compared to heterozygous female affected subjects. These findings could enhance genetic counseling and antenatal diagnosis of IN.

Keywords: Disease-causing variant; FERM domain containing 7; Infantile nystagmus; Phenotype difference.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Cytoskeletal Proteins / chemistry
  • Cytoskeletal Proteins / genetics*
  • Female
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Diseases, X-Linked / pathology
  • Hemizygote
  • Humans
  • Male
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation, Missense
  • Nystagmus, Congenital / genetics*
  • Nystagmus, Congenital / pathology
  • Pedigree
  • Penetrance
  • Polymorphism, Single Nucleotide*

Substances

  • Cytoskeletal Proteins
  • FRMD7 protein, human
  • Membrane Proteins

Supplementary concepts

  • X-Linked Infantile Nystagmus