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

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.