Abstract
Limb girdle muscular dystrophies (LGMD) are a large group of muscular disorders, with progressive shoulder and pelvic muscle weakness as the most relevant feature. They are classified as autosomal dominant (LGMD1) and autosomal recessive (LGMD2) forms. Up to now, eight genetically defined LGMD1 subtypes (LGMD1 A-H) have been identified [1, 9]. In 2001, the clinical and morphological phenotype of a novel form of LGMD type 1, affecting 32 subjects in a large Spanish family, was described [5]. According to subsequent molecular studies, the disease was demonstrated to be linked to the novel chromosomal locus 7q32.1–32.2. This genetically distinct form of autosomal dominant-LGMD was classified as LGMD1F [10] (OMIM #608423). Recently, using a whole genome sequencing approach, the causative mutation of the LGMD1F was identified in the termination codon of TNPO3, the gene coding for transportin 3. Molecular results at DNA, RNA and protein levels as well as morphological findings supported the pathogenic role of this mutation in LGMD1F [8]. Investigation by next-generation sequencing in further 4 members of the Spanish family, originating from Italy, confirmed the mutation in TNPO3 [13]. Up to now, beside this Italo-Spanish family, only one sporadic LGMD patient has been identified with a heterozygous point mutation in the TNPO3 gene [13]. In this patient we now report the long term clinical and radiological follow-up, morphological and immunochemical studies on patient muscle biopsy, and molecular studies by Real Time PCR and by cell transfection with the mutant cDNA.
Highlights
Limb girdle muscular dystrophies (LGMD) are a large group of muscular disorders, with progressive shoulder and pelvic muscle weakness as the most relevant feature
Western blot analysis of muscle homogenate using antibodies against transportin 3 showed that the band corresponding to the protein was of greatly reduced intensity in the patient compared to a control subject (Fig. 2)
Other aspects of the clinical phenotype considered as specific indicators of LGMD1F are dysphagia, arachnodactyly with or without finger contractures, and dysarthria [11]
Summary
Limb girdle muscular dystrophies (LGMD) are a large group of muscular disorders, with progressive shoulder and pelvic muscle weakness as the most relevant feature. In this patient we report the long term clinical and radiological follow-up, morphological and immunochemical studies on patient muscle biopsy, and Case report The patient was investigated at our institute when he was 38 years old because of slowly progressive difficulty in walking and climbing stairs presenting since the age of 35 years.
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