Alternative titles; symbols
SNOMEDCT: 726615005; ORPHA: 254361; DO: 0110285;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 8q24.3 | Muscular dystrophy, limb-girdle, autosomal recessive 17 | 613723 | Autosomal recessive | 3 | PLEC1 | 601282 |
A number sign (#) is used with this entry because of evidence that autosomal recessive limb-girdle muscular dystrophy-17 (LGMDR17) is caused by homozygous mutation in the PLEC gene (601282) on chromosome 8q24.
Autosomal recessive limb-girdle muscular dystrophy-17 (LGMDR17) is characterized by early childhood onset of proximal muscle weakness and atrophy without skin involvement. One family has shown rapid progression of the disorder in adolescence (summary by Gundesli et al., 2010).
For a discussion of genetic heterogeneity of autosomal recessive limb-girdle muscular dystrophy, see LGMDR1 (253600).
At the 229th ENMC international workshop, Straub et al. (2018) reviewed, reclassified, and/or renamed forms of LGMD. The proposed naming formula was 'LGMD, inheritance (R or D), order of discovery (number), affected protein.' Under this formula, LGMD2Q was renamed LGMDR17.
Gundesli et al. (2010) reported a consanguineous Turkish family in which 4 individuals had autosomal recessive limb-girdle muscular dystrophy with onset in childhood and progression during the teenage years. The proband began walking at age 3 years and had occasional falls and difficulties in climbing stairs. He remained relatively stable until age 14 years, when he became progressively weak, with Gowers sign, generalized muscle weakness, and lumbar lordosis. Serum creatine kinase was increased, and muscle biopsy showed dystrophic features, with variation in fiber size, internal nuclei, scattered necrotic fibers, and predominance of type 2 fibers. There was no cardiac or respiratory involvement, and intelligence was normal. There were 3 additional deceased family members similarly affected. One had stopped walking at age 24, and died at age 36 after being bedridden with near total atrophy of the muscles and multiple contractures. Affected individuals from 2 additional Turkish families had a similar disorder with onset in early childhood. None of the patients from the 3 families had any evidence of a skin disorder.
The transmission pattern of limb-girdle muscular dystrophy in the families reported by Gundesli et al. (2010) was consistent with autosomal recessive inheritance.
By homozygosity mapping followed by candidate gene sequencing of a Turkish family with autosomal recessive LGMD, Gundesli et al. (2010) identified a homozygous 9-bp deletion in the PLEC1 gene (601282.0010) as causative of the disorder. Subsequently, affected members of 2 additional Turkish families were found to carry the same mutation, and haplotype analysis indicated a founder effect. The 9-bp deletion was found to affect only the 1f isoform of plectin. Muscle biopsy from an affected individual showed significantly (100-fold) decreased expression of plectin isoform 1f mRNA and a 3-fold decrease of the plectin protein. Electron microscopy of patient muscle showed empty spaces between the sarcolemma and the contractile elements of the sarcomere, separation of membranes, loss of myofibrillar organization in some areas, and misalignment of the Z lines. These findings suggested that PLEC1 isoform-1f is a sarcolemma-associated protein with a specific role in skeletal muscle, and that lack of this isoform results in disruption of the myofiber without affecting other tissues.
Gundesli, H., Talim, B., Korkusuz, P., Balci-Hayta, B., Cirak, S., Akarsu, N. A., Topaloglu, H., Dincer, P. Mutation in exon 1f of PLEC, leading to disruption of plectin isoform 1f, causes autosomal-recessive limb-girdle muscular dystrophy. Am. J. Hum. Genet. 87: 834-841, 2010. [PubMed: 21109228] [Full Text: https://doi.org/10.1016/j.ajhg.2010.10.017]
Straub, V., Murphy, A., Udd, B. 229th ENMC international workshop: limb girdle muscular dystrophies--nomenclature and reformed classification, Naarden, the Netherlands, 17-19 March 2017. Neuromusc. Disord. 28: 702-710, 2018. [PubMed: 30055862] [Full Text: https://doi.org/10.1016/j.nmd.2018.05.007]