Open AccessRYR1 causing distal myopathy
Author(s) -
Laughlin Ruple S.,
Niu Zhiyv,
Wieben Eric,
Milone Margherita
Publication year - 2017
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.338
Subject(s) - ryr1 , muscle biopsy , medicine , weakness , compound heterozygosity , myopathy , central core disease , exome sequencing , congenital myopathy , muscle contracture , missense mutation , muscle weakness , proximal muscle weakness , malignant hyperthermia , ryanodine receptor , biopsy , phenotype , pathology , anatomy , genetics , biology , gene , receptor
Background Congenital myopathies due to ryanodine receptor ( RYR 1 ) mutations are increasingly identified and correlate with a wide range of phenotypes, most commonly that of malignant hyperthermia susceptibility and central cores on muscle biopsy with rare reports of distal muscle weakness, but in the setting of early onset global weakness. Methods We report a case of a patient presenting with childhood onset hand stiffness and adult onset progressive hand weakness and jaw contractures discovered to have two variants in the RYR 1 gene. Results The patient manifested with distal upper limb weakness which progressed to involve the distal lower limb, proximal upper limb, as well as the face in addition to limited jaw opening. Creatine kinase was mildly elevated with EMG findings supporting a myopathy. Muscle biopsy showed features consistent with centronuclear myopathy. Whole exome sequencing revealed a novel heterozygous pathogenic variant in RYR 1 (c.12315_12328del AGAAATCCAGTTCC , p.Glu4106Alafs*8), and a heterozygous missense variant (c.10648C>T, p.Arg3550Trp) of unknown significance in compound heterozygous state. Conclusion We expand the spectrum of RYR 1 ‐related myopathy with the description of a novel phenotype in an adult patient presenting with hand weakness and suggest considering RYR 1 analysis in the diagnosis of distal myopathies.