[A Japanese family with POMT2-related limb girdle muscular dystrophy]

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Mutations in the O-mannosyl-transferase 2 (POMT2) gene cause autosomal recessive limb girdle muscular dystrophy type 14 (LGMDR14).
• No Japanese patients with LGMDR14 have been previously reported.
• LGMDR14 is a rare inherited neuromuscular disorder affecting muscle strength and function.

Purpose of the Study:

• To report the first cases of LGMDR14 in a Japanese family.
• To characterize the clinical and genetic features of LGMDR14 in these patients.
• To investigate potential novel phenotypes associated with POMT2 mutations.

Main Methods:

• Genetic analysis to identify mutations in the POMT2 gene.
• Clinical examination and assessment of neurological and muscular symptoms.
• Classification of identified mutations using established guidelines (e.g., ACMG).

Main Results:

• Three patients from one Japanese family were diagnosed with LGMDR14.
• Identified a novel homozygous POMT2 mutation (c.1568A>G) in two patients and compound heterozygous mutations (c.1568A>G and c.869C>T) in the third.
• Patients exhibited difficulty walking, cognitive impairment, and severe hamstring muscle involvement.
• Two patients presented with eye abnormalities, a less commonly reported feature.

Conclusions:

• This study expands the known spectrum of LGMDR14 by reporting the first Japanese cases.
• The novel POMT2 mutations identified are classified as likely pathogenic.
• Eye abnormalities may represent a significant, though previously underreported, phenotype in LGMDR14 patients due to POMT2's retinal enzymatic activity.