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Nemaline myopathy is one of the major subtypes of congenital myopathy and is known to be caused by mutations in nine genes including cofilin-2 (CFL2).1 Typical nemaline myopathy presentations include proximal weakness, hypotonia, respiratory difficulties and facial weakness.1
This study was approved by The University of Western Australia Human Research Ethics Committee with written consent from patients.
After an uneventful birth the proband was admitted to the intensive care unit (ICU) with respiratory distress, although he did not require mechanical ventilation and was discharged after 5 days. A few weeks later he was readmitted following recurrent episodes of apnoea lasting seconds, associated with cyanosis. Most episodes presented after feeding and were aborted by stimulation. Upon admission to ICU, hypotension and respiratory acidosis were detected and orotracheal intubation and mechanical ventilation initiated. After correcting metabolic disturbances, the patient remained hypotonic, though fully awake and alert when taken off sedation. Extraocular movements were estimated to be normal and deep tendon reflexes were present. Head circumference was on the third centile. Extubation failed and the patient required 24-h continuous ventilation support before passing away at 12 months. Nerve conduction studies, MRI, EEG and echocardiography were normal. An electromyograph (EMG) showed apparent myotonic discharges and serum creatine kinase (CK) was mildly elevated.
The proband was Saudi Arabian and his parents were first cousins (figure 1A). Two cousins of the proband (figure 1A III:3 and III.4) had a similar disease, both requiring 24-h mechanical ventilation. One cousin (III:3) passed away at 14 months, while the 10-month-old brother (III:4) is still on 24-h ventilation. Due to the severity of the disease in the proband, diagnostic mutation analysis of SMN1 and ACTA1 was performed, but both were excluded.
Contributors RWO contributed to the drafting and revision of the manuscript and for its content, study concept and design, analysis and interpretation of data and performed the molecular analysis of the patient. AAlS was the clinician in charge of the patient, led the initial investigations and clinical analysis into the patient and oversaw the review of the clinical information on the patient. DS performed pathology analysis for the patient, contributed to writing the pathology section of the manuscript and interpretation of histological data. AA contributed to the drafting and revision of the manuscript, drafting/revising the manuscript for content and analysis or interpretation of data. KSY developed the next generation sequencing analysis pipeline and contributed to drafting/revising the manuscript for content. GR performed the molecular analysis of the patient, contributed to drafting the manuscript, drafting/revising the manuscript for content and analysis and/or interpretation of data. RMD assisted in conceptualising the study and contributed to drafting/revising the manuscript for content. VA was responsible for performing next generation sequencing of patient's DNA and contributed to drafting/revising the manuscript for content. RJA oversaw the process of next generation sequencing and contributed to drafting/revising the manuscript for content. NGL conceptualised the study, had overall responsibility for coordinating the study, assisted with drafting and revision of the manuscript and analysis of data, drafting/revising the manuscript for content, including medical writing for content, study concept or design, analysis or interpretation of data.
Funding This research was supported by the National Health and Medical Research Council of Australia (Fellowships APP1035955 to GR and APP1002147 to NGL, and project grant APP1022707 to NGL).
Competing interests None.
Ethics approval The University of Western Australia.
Provenance and peer review Not commissioned; externally peer reviewed.
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