TMEM5-associated dystroglycanopathy presenting with CMD and mild limb-girdle muscle involvement

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Dystroglycanopathies are neurodegenerative disorders resulting from impaired alpha-dystroglycan glycosylation.
• Mutations in the TMEM5 gene have recently been associated with severe forms of these conditions.

Observation:

• A case study of an Italian boy with delayed development, mild muscle weakness, and specific brain malformations (polymicrogyria) was analyzed.
• The patient presented with moderate intellectual disability, cochlear dysplasia, and a known TMEM5 mutation (p.A47Rfs*42).

Findings:

• Targeted next-generation sequencing confirmed the TMEM5 mutation.
• The patient exhibited a milder muscular phenotype and unique structural brain abnormalities compared to previously reported severe cases.

Implications:

• This case expands the clinical and genetic spectrum of TMEM5-associated disorders.
• Understanding these variations is crucial for accurate diagnosis and potential therapeutic strategies in dystroglycanopathies.