p.S143F mutation in lamin A/C: a new phenotype combining myopathy and progeria

Area of Science:

• Genetics
• Molecular Biology
• Pediatrics

Background:

• Mutations in the LMNA gene are associated with Hutchinson-Gilford progeria syndrome and Emery-Dreifuss muscular dystrophy.
• These conditions present with distinct clinical features, including premature aging and muscle degeneration, respectively.

Purpose of the Study:

• To identify the genetic cause of a rare condition in a young girl exhibiting both myopathy and progeroid features.
• To characterize a novel mutation in the LMNA gene and its phenotypic consequences.

Main Methods:

• Clinical assessment of the patient, including detailed phenotyping.
• Genetic analysis to identify mutations in the LMNA gene.
• Comparison of the identified mutation with known pathogenic variants.

Main Results:

• The patient presented with early-onset myopathy and axial weakness within the first year of life.
• Later development of progeroid features including growth failure, sclerodermatous skin, and osteolytic lesions.
• Identification of a novel de novo missense mutation, S143F, in the LMNA gene.

Conclusions:

• This report describes the first patient with a combined phenotype of myopathy and progeria due to a single LMNA gene mutation.
• The S143F mutation in LMNA expands the known spectrum of laminopathies.
• This finding highlights the critical role of lamins A and C in nuclear envelope integrity and organismal development.