Copy number analysis reveals a novel multiexon deletion of theCOLQgene in congenital myasthenia.
Congenital myasthenic syndrome (CMS) is genetically and clinically heterogeneous.1Despite a considerable number of causal genes discovered, many patients are left without a specific diagnosis after genetic testing. The presumption is that novel genes yet to be discovered will account for the majority of such patients. However, it is also possible that we are neglecting a type of genetic variation: copy number changes (>50 bp) as causal for some of these patients. Next-generation sequencing (NGS) can simultaneously screen all known causal genes2and is increasingly being validated to have a potential to identify copy number changes.3We present a CMS case who did not receive a genetic diagnosis from previous Sanger sequencing, but through a novel copy number analysis algorithm integrated into our targeted NGS panel, we discovered a novel copy number mutation in theCOLQgene and made a genetic diagnosis. This discovery expands the genotype-phenotype correlation of CMS, leads to improved genetic counsel, and allows for specific pharmacologic treatment.1.
Department of Neurology (W.W., J.J.), China-Japan Friendship Hospital, Beijing, China; Department of Neurology (W.W., C.J.K.), Department of Laboratory Medicine and Pathology (Y.W.), Department of Health Sciences Research (C.W.), and Department of Medical Genetics (C.J.K.), Mayo Clinic, Rochester, MN.
Wei
W
Wang
Department of Neurology (W.W., J.J.), China-Japan Friendship Hospital, Beijing, China; Department of Neurology (W.W., C.J.K.), Department of Laboratory Medicine and Pathology (Y.W.), Department of Health Sciences Research (C.W.), and Department of Medical Genetics (C.J.K.), Mayo Clinic, Rochester, MN.
Yanhong
Y
Wu
Department of Neurology (W.W., J.J.), China-Japan Friendship Hospital, Beijing, China; Department of Neurology (W.W., C.J.K.), Department of Laboratory Medicine and Pathology (Y.W.), Department of Health Sciences Research (C.W.), and Department of Medical Genetics (C.J.K.), Mayo Clinic, Rochester, MN.
Chen
C
Wang
Department of Neurology (W.W., J.J.), China-Japan Friendship Hospital, Beijing, China; Department of Neurology (W.W., C.J.K.), Department of Laboratory Medicine and Pathology (Y.W.), Department of Health Sciences Research (C.W.), and Department of Medical Genetics (C.J.K.), Mayo Clinic, Rochester, MN.
Jinsong
J
Jiao
Department of Neurology (W.W., J.J.), China-Japan Friendship Hospital, Beijing, China; Department of Neurology (W.W., C.J.K.), Department of Laboratory Medicine and Pathology (Y.W.), Department of Health Sciences Research (C.W.), and Department of Medical Genetics (C.J.K.), Mayo Clinic, Rochester, MN.
Christopher J
CJ
Klein