Generation of two isogenic induced pluripotent stem cell lines from a 4-month-old severe nemaline myopathy patient with a heterozygous dominant c.553C > A (p.Arg183Ser) variant in the ACTA1 gene

• DOI: 10.1016/j.scr.2021.102273
• Publication Date: 2021-02-26T18:11:02Z
• Authors: Joshua S. Clayton; Carolin K. Scriba; Norma B. Romero; Edoardo Malfatti; Safaa Saker; Thierry Larmonier; Kristen J. Nowak; Gianina Ravenscroft; Nigel G. Laing; Rhonda L. Taylor
• Keywords: 0301 basic medicine; MESH: Mutation ;; MESH: Mutation; QH301-705.5; MESH: Female ;; [SDV]Life Sciences [q-bio]; Induced Pluripotent Stem Cells; MESH: Actins / genetics; MESH: Infant ;; Myopathies, Nemaline; MESH: Induced Pluripotent Stem Cells*; 576; 03 medical and health sciences; 616; Humans; Biology (General); Muscle, Skeletal; MESH: Humans; MESH: Actins / genetics ;; MESH: Muscle; MESH: Induced Pluripotent Stem Cells* ;; Infant; Skeletal; MESH: Infant; Actins; MESH: Humans ;; [SDV] Life Sciences [q-bio]; MESH: Muscle, Skeletal ;; Mutation; MESH: Myopathies, Nemaline* / genetics; Female; Nemaline* / genetics; MESH: Myopathies; MESH: Female

Nemaline myopathy (NM) is a congenital myopathy typically characterized by skeletal muscle weakness and the presence of abnormal thread- or rod-like structures (nemaline bodies) in myofibres. Pathogenic variants in the skeletal muscle alpha actin gene, ACTA1, cause approximately 25% of all NM cases. We generated two induced pluripotent stem cell lines from lymphoblastoid cells of a 4-month-old female with severe NM harbouring a dominant variant in ACTA1 (c.553C > A). The isogenic lines displayed characteristic iPSC morphology, expressed pluripotency markers, differentiated into cells of all three germ layers, and possessed normal karyotypes. These lines could be useful models of human ACTA1 disease.