Jaka Oihane, Azpitarte Margarita, Paisán-Ruiz Coro, Zulaika Miren, Casas-Fraile Leire, Sanz Raúl, Trevisiol Nathalie, Levy Nicolas, Bartoli Marc, Krahn Martin, López de Munain Adolfo, Sáenz Amets
Neurosciences Area, Biodonostia Institute, Hospital Universitario Donostia, 20014, San Sebastián, Spain.
Muscle Nerve. 2014 Sep;50(3):448-53. doi: 10.1002/mus.24263. Epub 2014 Aug 5.
Limb-girdle muscular dystrophy type 2A (LGMD2A) due to mutations in the CAPN3 gene is one of the most common of autosomal recessive limb-girdle muscular dystrophies. We describe a patient who had a typical LGMD2A phenotype and posterior compartment involvement on MRI. Different genetic analyses were performed, including microarray analysis. There was an apparently homozygous mutation in exon 24, c.2465G>T, p.(822Leuext62), and a lack of correlation in the disease segregation analyses. This suggested the presence of a genomic rearrangement. In fact, a heterozygous deletion of the entire CAPN3 gene was found. This novel deletion comprised the terminal region of the GANC gene and the entire CAPN3 gene. This finding points out the need to reconsider and adapt our current strategy of molecular diagnosis in order to detect these types of genomic rearrangements that escape standard mutation screening procedures.
由钙蛋白酶3（CAPN3）基因突变引起的2A型肢带型肌营养不良（LGMD2A）是常染色体隐性肢带型肌营养不良中最常见的类型之一。我们描述了一名具有典型LGMD2A表型且MRI显示后肌群受累的患者。进行了不同的基因分析，包括微阵列分析。在第24外显子中存在一个明显的纯合突变，即c.2465G>T，p.（822Leuext62），并且在疾病分离分析中缺乏相关性。这提示存在基因组重排。事实上，发现了整个CAPN3基因的杂合缺失。这个新的缺失包括GAN C基因的末端区域和整个CAPN3基因。这一发现指出有必要重新考虑并调整我们当前的分子诊断策略，以便检测出这些逃避标准突变筛查程序的基因组重排类型。
