LMNA相关肌营养不良患儿的表型-基因型分析与LMNA突变体功能分析.pdfVIP

Abstract progressing trunk and neck-axis muscle weakness, poor head control, joint contractureswith progression from distaljointsto proximaljoints, spinal deformity, hypotonia, hyporeflexia or abolition of tendon reflex; EDMD cases presented early childhood-onsent slowly progressing scapular and fibular muscle weakness and atrophy, joint contractures with progression from proximal joints to distal joints, spinal deformity, hypotonia, hyporeflexia or abolition of tendon reflex. Most cases had mild or moderate elevation of CK levels, myogenic injury examined by EMG, disordersofcardiacconductionontheelectrocardiogramandnormalbrainMRI. . 2 Pathologicalfeatures:musclebiopsieswereperformed on 12in 17casesfor 、 routinehistological stainsandobservationoftheultrastructureofmusclefibersunder electron microscopy. Dystrophic changes or myopathic changes associated with inflammation on early-onset L-CMD were observed by HE staining. The ultrastructure of fibers under electron microscopy showed focal or extended disruption of filament, indistinct sarcomeres, many vacuoles in the muscle fibers, increased adipose and connective tissue, abnormal nuclear morphology with heterochromatin condensation, focal loss of nuclear membrane, accumulation of mitochondriaaroundthenucleus,nuclearbands,andnucleolarholes. 3 Genotypefeatures:the 17casesweregeneticallyidentifiedbythedetectionof 、 LMNA mutations. The mutations including 13 missense mutations, 3 deletion mutations and 1 splicing mutation were all heterozygous. 16 kinds of mutations including 8novel mutationswere found.The sourcesofmutations on 14caseswere verified: 1 paternal mutation and 13 de novo mutations. Mutations(c.91GA 、 c.94_96delAAG c.