Novel large deletion in the ACTA1 gene in a child with autosomal recessive nemaline myopathy.
Nemaline myopathy (NM) is a genetically and clinically heterogeneous disorder resulting from a disruption of the thin filament proteins of the striated muscle sarcomere. The disorder is typically characterized by muscle weakness including the face, neck, respiratory, and limb muscles and is clinically classified based on the age of onset and severity. Mutations in the ACTA1 gene contribute to a significant proportion of NM cases. The majority of ACTA1 gene mutations are missense mutations causing autosomal dominant NM by producing an abnormal protein. However, approximately 10% of ACTA1 gene mutations are associated with autosomal recessive NM; these mutations are associated with loss of protein function. We report the first case of a large deletion in the ACTA1 gene contributing to autosomal recessive NM. This case illustrates the importance of understanding disease mechanisms at the molecular level to accurately infer the inheritance pattern and potentially aid with clinical management.
GeneDx, Gaithersburg, MD, USA.
Bethany
B
Friedman
Genetics and Metabolism, Children's National Medical Center, Washington, DC, USA.
Kara
K
Simpson
Neurology, Children's National Medical Center, Washington, DC, USA.
Carolina
C
Tesi-Rocha
Department of Pathology, University of Utah, Salt Lake City, UT, USA.
Delu
D
Zhou
Department of Pathology, University of Utah, Salt Lake City, UT, USA.
Cheryl A
CA
Palmer
GeneDx, Gaithersburg, MD, USA. Electronic address: ssuchy@genedx.com.
Sharon F
SF
Suchy
D000199:Actins / Q000235:genetics*; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D018482:Muscle, Skeletal / Q000473:pathology; D017696:Myopathies, Nemaline / Q000235:genetics* / Q000473:pathology; D017384:Sequence Deletion
D000199:Actins
ACTA1; Deletion; Dominant negative; Loss of function; Nemaline myopathy