Author/Editor		Meznarič, M; Gonzalez-Quereda, L; Gallardo, E; de Luna, N; Gallano, P; Fanin, M; Angelini, C; Peterlin, B; Zidar, J
Title		Abnormal expression of dysferlin in skeletal muscle and monocytes supports primary dysferlinopathy in patients with one mutated allele
Type		članek
Source		Eur J Neurol
Vol. and No.		Letnik 18, št. 7
Publication year		2011
Volume		str. 1021-3
Language		eng
Abstract		Background: In some cases, a definitive confirmation of dysferlinopathy cannot be achieved by DNA test, because the mutation is detected in one allele only. Patients and methods: Dysferlin expression in skeletal muscle and peripheral blood monocytes (PBM) was studied by Western blot in two unrelated adult patients. The comparative C(T) method (DeltaDeltaC(T) ) was used to calculate relative changes in dysferlin mRNA determined from real-time quantitative PCR experiments. The dysferlin gene was studied by direct sequencing of cDNA and genomic DNA and by Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. Results: A comparable severe reduction in dysferlin was demonstrated in both skeletal muscle and PBM. The expression of dysferlin mRNA was significantly reduced. A novel mutation in exon 47 (c.5289G>C) of the dysferlin gene in the heterozygous state, causing an amino acid change (p.Glu1763Asp), was detected in both patients. The MLPA analysis did not reveal any deletion or duplication. Conclusions: Dysferlin and/or dysferlin mRNA abnormalities are diagnostic for dysferlinopathy when mutational analysis detects a mutation in one allele only. Analysis of dysferlin mRNA can be helpful for distinguishing symptomatic heterozygotes from such patients.
Descriptors		MUSCULAR DYSTROPHY MUSCLE, SKELETAL MUSCLE PROTEINS HETEROZYGOTE RNA, MESSENGER DNA MUTATIONAL ANALYSIS MONOCYTES BLOTTING, WESTERN