TY - JOUR
T1 - Clinical and genetic characterization of an Italian family with slow-channel syndrome
AU - Angelini, Corrado
AU - Lispi, Ludovico
AU - Salvoro, Cecilia
AU - Mostacciuolo, Maria Luisa
AU - Vazza, Giovanni
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Introduction: The slow-channel congenital myasthenic syndrome (SCCMS) is a postsynaptic form of congenital myasthenic syndromes (CMSs), a clinically heterogeneous group of disorders caused by genetic defects leading to an abnormal signal transmission at the endplate. Methods: We report clinical and molecular data of a multigenerational family in which the presentation of a progressive proximal-distal weakness with ocular involvement led to a number of different clinical diagnoses. Results: A comprehensive genetic study which included whole-genome linkage analysis and whole-exome sequencing identified a heterozygous missense substitution (c.721C>T, p.L241F) in the ε subunit of the acetylcholine receptor (CHRNE) that was consistent with clinical weakness in all patients. Discussion: SCCMS is characterized by a broad and heterogeneous clinical phenotype in which disease onset, symptoms, severity, and progression can be highly variable even between family members. The identification of a CHRNE mutation allowed to make the definitive diagnosis of CMS in this family and contributed to define the clinical spectrum of this disease.
AB - Introduction: The slow-channel congenital myasthenic syndrome (SCCMS) is a postsynaptic form of congenital myasthenic syndromes (CMSs), a clinically heterogeneous group of disorders caused by genetic defects leading to an abnormal signal transmission at the endplate. Methods: We report clinical and molecular data of a multigenerational family in which the presentation of a progressive proximal-distal weakness with ocular involvement led to a number of different clinical diagnoses. Results: A comprehensive genetic study which included whole-genome linkage analysis and whole-exome sequencing identified a heterozygous missense substitution (c.721C>T, p.L241F) in the ε subunit of the acetylcholine receptor (CHRNE) that was consistent with clinical weakness in all patients. Discussion: SCCMS is characterized by a broad and heterogeneous clinical phenotype in which disease onset, symptoms, severity, and progression can be highly variable even between family members. The identification of a CHRNE mutation allowed to make the definitive diagnosis of CMS in this family and contributed to define the clinical spectrum of this disease.
KW - CHRNE mutation
KW - Congenital myasthenic syndrome
KW - Linkage analysis
KW - Slow-channel congenital myasthenic syndrome
KW - Whole-exome sequencing
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U2 - 10.1007/s10072-018-3645-2
DO - 10.1007/s10072-018-3645-2
M3 - Article
AN - SCOPUS:85058419466
JO - Neurological Sciences
JF - Neurological Sciences
SN - 1590-1874
ER -