FOXJ1 Variants Causing Primary Ciliary Dyskinesia with Hydrocephalus: A Case Report from Japan

Area of Science:

• Genetics
• Respiratory Medicine
• Rare Diseases

Background:

• Primary ciliary dyskinesia (PCD) is a genetic disorder impacting motile cilia function, typically inherited in autosomal recessive or X-linked patterns.
• The FOXJ1 gene plays a crucial role in ciliogenesis and is associated with autosomal-dominant PCD when mutated.

Observation:

• A 29-year-old Japanese woman presented with PCD, characterized by situs inversus, congenital heart disease, infertility, and hydrocephalus.
• Genetic analysis revealed a heterozygous frameshift mutation in exon 3 of the FOXJ1 gene, a novel finding in this patient.
• Notably, the patient exhibited normal nasal nitric oxide levels, a common biomarker for PCD.

Findings:

• This case represents the first report of PCD caused by a FOXJ1 variant in Japan.
• The patient's PCD was linked to a heterozygous de novo mutation in FOXJ1, expanding the known genetic spectrum of the disease.
• Long-term macrolide therapy demonstrated significant effectiveness in managing the patient's condition.

Implications:

• This case highlights the genetic heterogeneity of PCD and the potential for novel FOXJ1 mutations to cause the disease.
• The successful treatment with macrolides suggests this therapeutic approach may be beneficial for PCD patients with specific genetic underpinnings.
• Further research into FOXJ1 variants and their clinical manifestations is warranted for improved diagnosis and management of PCD.