Gonorazky, HD;
Marshall, CR;
Al-Murshed, M;
Hazrati, L-N;
Thor, MG;
Hanna, MG;
Mannikko, R;
... Yoon, G; + view all
(2017)
Congenital myopathy with "corona" fibres, selective muscle atrophy, and craniosynostosis associated with novel recessive mutations in SCN4A.
Neuromuscular Disorders
, 27
(6)
pp. 574-580.
10.1016/j.nmd.2017.02.001.
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Abstract
We describe two brothers with lower facial weakness, highly arched palate, scaphocephaly due to synostosis of the sagittal and metopic sutures, axial hypotonia, proximal muscle weakness, and mild scoliosis. The muscle MRI of the younger sibling revealed a selective pattern of atrophy of the gluteus maximus, adductor magnus and soleus muscles. Muscle biopsy of the younger sibling revealed myofibres with internalized nuclei, myofibrillar disarray, and “corona” fibres. Both affected siblings were found to be compound heterozygous for c.3425G>A (p.Arg1142Gln) and c.1123T>C (p.Cys375Arg) mutations in SCN4A on exome sequencing, and the parents were confirmed carriers of one of the mutations. Electrophysiological characterization of the mutations revealed the Cys375Arg confers full and Arg1142Gln mild partial loss-of-function. Loss of function of the Nav1.4 channel leads to a decrement of the action potential and subsequent reduction of muscle contraction. The unusual muscle biopsy features suggest a more complex pathomechanism, and broaden the phenotype associated with SCN4A mutations.
| Type: | Article |
|---|---|
| Title: | Congenital myopathy with "corona" fibres, selective muscle atrophy, and craniosynostosis associated with novel recessive mutations in SCN4A |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.nmd.2017.02.001 |
| Publisher version: | http://doi.org/10.1016/j.nmd.2017.02.001 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Neurosciences, Neurosciences & Neurology, Congenital myopathy, SCN4A, Corona fibres, Channelopathies, NECKLACE FIBERS, CENTRONUCLEAR MYOPATHY, MYASTHENIC SYNDROME, PERIODIC PARALYSIS, NA(V)1.4, MARKER |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1544744 |
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