Pathogenic mutations and sequence variants within mitofusin 2 gene in Polish patients with different hereditary...

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Mitochondrin-2 (MFN2) gene mutations were initially thought to be a primary cause of hereditary motor and sensory neuropathy type 2 (HMSN II).
• Recent findings indicate a lower-than-expected frequency of MFN2 mutations in HMSN II patients.
• No systematic studies on MFN2 gene mutations in Polish HMSN IIa patients have been conducted.

Purpose of the Study:

• To investigate the frequency and spectrum of MFN2 gene mutations in a Polish cohort of hereditary motor and sensory neuropathy type 2 patients.
• To assess the diagnostic utility of MFN2 gene analysis in Polish HMSN II patients with diverse clinical presentations.

Main Methods:

• Genetic analysis of the MFN2 gene was performed in 67 Polish patients diagnosed with hereditary motor and sensory neuropathy type 2.
• Sequencing and variant analysis were employed to identify mutations, sequence variants of unknown pathogenic status, rare variants, and common polymorphisms.

Main Results:

• Pathogenic MFN2 mutations were identified in 4.5% of the studied patients.
• Three pathogenic mutations, three variants of unknown significance, nine rare variants, and six common polymorphisms were detected.
• The presence of multiple MFN2 sequence variants in individual patients suggests a potential cumulative effect on the HMSN II phenotype.

Conclusions:

• The MFN2 gene should be considered in the molecular diagnostics of hereditary motor and sensory neuropathy type 2 in Poland.
• The exact position of MFN2 gene analysis in the routine diagnostic algorithm for HMSN II remains undetermined due to the observed variant frequencies and unknown significance of some findings.