ObjectiveNext-generation sequencing (NGS) was applied in molecularly undiagnosed asymptomatic or paucisymptomatic hyperCKemia to investigate whether this technique might allow detection of the genetic basis of the condition.MethodsSixty-six patients with undiagnosed asymptomatic or paucisymptomatic hyperCKemia, referred to tertiary neuromuscular centers over an approximately 2-year period, were analyzed using a customized, targeted sequencing panel able to investigate the coding exons and flanking intronic regions of 78 genes associated with limb-girdle muscular dystrophies, rhabdomyolysis, and metabolic and distal myopathies.ResultsA molecular diagnosis was reached in 33 cases, corresponding to a positive diagnostic yield of 50%. Variants of unknown significance were found in 17 patients (26%), whereas 16 cases (24%) remained molecularly undefined. The major features of the diagnosed cases were mild proximal muscle weakness (found in 27%) and myalgia (in 24%). Fourteen patients with a molecular diagnosis and mild myopathic features on muscle biopsy remained asymptomatic at a 24-month follow-up.ConclusionsThis study of patients with undiagnosed hyperCKemia, highlighting the advantages of NGS used as a first-tier diagnostic approach in genetically heterogeneous conditions, illustrates the ongoing evolution of molecular diagnosis in the field of clinical neurology. Isolated hyperCKemia can be the sole feature alerting to a progressive muscular disorder requiring careful surveillance.

Rubegni, A., Malandrini, A., Dosi, C., Astrea, G., Baldacci, J., Battisti, C., et al. (2019). Next-generation sequencing approach to hyperCKemia: A 2-year cohort study. NEUROLOGY. GENETICS, 5(5), 1-11 [10.1212/NXG.0000000000000352].

Next-generation sequencing approach to hyperCKemia: A 2-year cohort study

Malandrini A.
Membro del Collaboration Group
;
Battisti C.
Membro del Collaboration Group
;
Dotti M. T.
Membro del Collaboration Group
;
Federico A.
Membro del Collaboration Group
;
Giannini F.
Membro del Collaboration Group
;
Grosso S.
Membro del Collaboration Group
;
Sacchini M.
Membro del Collaboration Group
;
Volpi N.
Membro del Collaboration Group
;
2019-01-01

Abstract

ObjectiveNext-generation sequencing (NGS) was applied in molecularly undiagnosed asymptomatic or paucisymptomatic hyperCKemia to investigate whether this technique might allow detection of the genetic basis of the condition.MethodsSixty-six patients with undiagnosed asymptomatic or paucisymptomatic hyperCKemia, referred to tertiary neuromuscular centers over an approximately 2-year period, were analyzed using a customized, targeted sequencing panel able to investigate the coding exons and flanking intronic regions of 78 genes associated with limb-girdle muscular dystrophies, rhabdomyolysis, and metabolic and distal myopathies.ResultsA molecular diagnosis was reached in 33 cases, corresponding to a positive diagnostic yield of 50%. Variants of unknown significance were found in 17 patients (26%), whereas 16 cases (24%) remained molecularly undefined. The major features of the diagnosed cases were mild proximal muscle weakness (found in 27%) and myalgia (in 24%). Fourteen patients with a molecular diagnosis and mild myopathic features on muscle biopsy remained asymptomatic at a 24-month follow-up.ConclusionsThis study of patients with undiagnosed hyperCKemia, highlighting the advantages of NGS used as a first-tier diagnostic approach in genetically heterogeneous conditions, illustrates the ongoing evolution of molecular diagnosis in the field of clinical neurology. Isolated hyperCKemia can be the sole feature alerting to a progressive muscular disorder requiring careful surveillance.
2019
Rubegni, A., Malandrini, A., Dosi, C., Astrea, G., Baldacci, J., Battisti, C., et al. (2019). Next-generation sequencing approach to hyperCKemia: A 2-year cohort study. NEUROLOGY. GENETICS, 5(5), 1-11 [10.1212/NXG.0000000000000352].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1095766