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

Area of Science:

• Genetics
• Ophthalmology
• Molecular Biology

Background:

• Infantile nystagmus (IN) is an involuntary eye movement disorder typically presenting within the first six months of life.
• The X-linked inheritance pattern with incomplete penetrance in females is common for IN.
• The FERM domain containing 7 (FRMD7) gene is a primary genetic cause of infantile nystagmus.

Observation:

• A large Han-Chinese family exhibited a spectrum of phenotypes, ranging from unaffected individuals to those with manifest nystagmus.
• Clinical examinations and genetic sequencing (exome and Sanger) were conducted on the family.
• A novel FRMD7 variant, c.47T>C (p.Phe16Ser), was identified as the likely cause of IN in this cohort.

Findings:

• The identified FRMD7 c.47T>C variant demonstrated incomplete penetrance in female carriers.
• Affected males (hemizygous) presented with more severe clinical manifestations than affected females (heterozygous).
• This genetic variant provides a specific molecular basis for infantile nystagmus within this family.

Implications:

• These results contribute to a deeper understanding of the genetic underpinnings of infantile nystagmus.
• The findings can improve the accuracy of genetic counseling for families affected by IN.
• Enhanced genetic knowledge facilitates better antenatal diagnostic strategies for X-linked nystagmus.