% 613530

MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 1H; LGMD1H


Cytogenetic location: 3p25.1-p23     Genomic coordinates (GRCh38): 3:13,200,001-32,000,000


Gene-Phenotype Relationships
Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
3p25.1-p23 Muscular dystrophy, limb-girdle, type 1H 613530 AD 2
Clinical Synopsis
 
Phenotypic Series
 

INHERITANCE
- Autosomal dominant
MUSCLE, SOFT TISSUES
- Proximal muscle weakness, upper and lower limbs
- Hip girdle muscle atrophy
- Shoulder girdle muscle atrophy
- Calf hypertrophy
- EMG shows myopathic pattern
- Muscle biopsy shows abnormal fiber size and variation
- Increased connective tissue
- Centralized nuclei, rare
- Ragged red fibers
- Subsarcolemmal mitochondrial accumulation
- Cytochrome c oxidase-negative fibers
- Mitochondrial DNA deletions
NEUROLOGIC
Peripheral Nervous System
- Hyporeflexia
LABORATORY ABNORMALITIES
- Increased serum creatine kinase
MISCELLANEOUS
- Onset of muscle weakness in fifth decade
- Onset of calf hypotrophy may occur earlier
- Slowly progressive
- Incomplete penetrance
- Variable expressivity
- One family has been reported (as of August 2010)

TEXT

Description

Limb-girdle muscular dystrophy type 1H (LGMD1H) is an autosomal dominant disorder characterized by adult onset of progressive proximal muscle weakness affecting both the upper and lower limbs (Bisceglia et al., 2010).

For a phenotypic description and a discussion of genetic heterogeneity of autosomal dominant limb-girdle muscular dystrophy, see LGMDD1 (603511).


Clinical Features

Bisceglia et al. (2010) reported a 4-generation family from southern Italy segregating limb-girdle muscular dystrophy in an autosomal dominant pattern of inheritance. Five family members presented with slowly progressive muscle weakness, initially affecting the lower limbs and later involving the upper limbs, with onset between 39 and 50 years of age. There was hypotrophy of upper and lower limb-girdle muscles, hyporeflexia, calf hypertrophy, and increased serum creatine kinase. A second group of younger family members had a possibly less severe phenotype with calf hypertrophy, but no muscle weakness and normal serum creatine kinase when examined. These individuals were considered affected for linkage analysis. EMG studies in 2 older patients showed a myopathic pattern with decreased duration of motor unit potentials and no evidence of denervation. Skeletal muscle biopsies of 4 older affected individuals showed abnormal fiber type size and shape variation, increased connective tissues, and occasional centralized nuclei. One biopsy showed ragged-red fibers with subsarcolemmal accumulation of mitochondria, and 2 biopsies showed absence of cytochrome c oxidase staining as well as evidence of mtDNA deletions. Overall, the biopsy results suggested a defect in mitochondrial function.


Mapping

By genomewide linkage analysis, followed by haplotype analysis, of a 4-generation Italian family with LGMD, Bisceglia et al. (2010) identified a candidate disease locus, which the authors termed LGMD1H, within a 25-cM region on chromosome 3p25.1-p23 between markers D3S1263 and D3S1277 (2-point lod score of 3.23 at markers D3S3613 and D3S1286; nonparametric p value of 0.0004). Two unaffected individuals, aged 14 and 30 years, respectively, shared the disease haplotype. Four candidate genes in the region, CAV3 (601253), CAPN7 (606300), MGC15763, and CMYA1 (609777), were analyzed but no pathogenic mutations were found.


REFERENCES

  1. Bisceglia, L., Zoccolella, S., Torraco, A., Piemontese, M. R., Dell'Aglio, R., Amati, A., De Bonis, P., Artuso, L., Copetti, M., Santorelli, F. M., Serlenga, L., Zelante, L., Bertini, E., Petruzzella, V. A new locus on 3p23-p25 for an autosomal-dominant limb-girdle muscular dystrophy, LGMD1H. Europ. J. Hum. Genet. 18: 636-641, 2010. [PubMed: 20068593, images, related citations] [Full Text]


Creation Date:
Cassandra L. Kniffin : 8/18/2010
carol : 09/27/2018
terry : 12/10/2010
wwang : 8/20/2010
ckniffin : 8/19/2010

% 613530

MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 1H; LGMD1H


SNOMEDCT: 771334000;   DO: 0110303;  


Cytogenetic location: 3p25.1-p23     Genomic coordinates (GRCh38): 3:13,200,001-32,000,000


Gene-Phenotype Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
3p25.1-p23 Muscular dystrophy, limb-girdle, type 1H 613530 Autosomal dominant 2

TEXT

Description

Limb-girdle muscular dystrophy type 1H (LGMD1H) is an autosomal dominant disorder characterized by adult onset of progressive proximal muscle weakness affecting both the upper and lower limbs (Bisceglia et al., 2010).

For a phenotypic description and a discussion of genetic heterogeneity of autosomal dominant limb-girdle muscular dystrophy, see LGMDD1 (603511).


Clinical Features

Bisceglia et al. (2010) reported a 4-generation family from southern Italy segregating limb-girdle muscular dystrophy in an autosomal dominant pattern of inheritance. Five family members presented with slowly progressive muscle weakness, initially affecting the lower limbs and later involving the upper limbs, with onset between 39 and 50 years of age. There was hypotrophy of upper and lower limb-girdle muscles, hyporeflexia, calf hypertrophy, and increased serum creatine kinase. A second group of younger family members had a possibly less severe phenotype with calf hypertrophy, but no muscle weakness and normal serum creatine kinase when examined. These individuals were considered affected for linkage analysis. EMG studies in 2 older patients showed a myopathic pattern with decreased duration of motor unit potentials and no evidence of denervation. Skeletal muscle biopsies of 4 older affected individuals showed abnormal fiber type size and shape variation, increased connective tissues, and occasional centralized nuclei. One biopsy showed ragged-red fibers with subsarcolemmal accumulation of mitochondria, and 2 biopsies showed absence of cytochrome c oxidase staining as well as evidence of mtDNA deletions. Overall, the biopsy results suggested a defect in mitochondrial function.


Mapping

By genomewide linkage analysis, followed by haplotype analysis, of a 4-generation Italian family with LGMD, Bisceglia et al. (2010) identified a candidate disease locus, which the authors termed LGMD1H, within a 25-cM region on chromosome 3p25.1-p23 between markers D3S1263 and D3S1277 (2-point lod score of 3.23 at markers D3S3613 and D3S1286; nonparametric p value of 0.0004). Two unaffected individuals, aged 14 and 30 years, respectively, shared the disease haplotype. Four candidate genes in the region, CAV3 (601253), CAPN7 (606300), MGC15763, and CMYA1 (609777), were analyzed but no pathogenic mutations were found.


REFERENCES

  1. Bisceglia, L., Zoccolella, S., Torraco, A., Piemontese, M. R., Dell'Aglio, R., Amati, A., De Bonis, P., Artuso, L., Copetti, M., Santorelli, F. M., Serlenga, L., Zelante, L., Bertini, E., Petruzzella, V. A new locus on 3p23-p25 for an autosomal-dominant limb-girdle muscular dystrophy, LGMD1H. Europ. J. Hum. Genet. 18: 636-641, 2010. [PubMed: 20068593] [Full Text: https://doi.org/10.1038/ejhg.2009.235]


Creation Date:
Cassandra L. Kniffin : 8/18/2010

Edit History:
carol : 09/27/2018
terry : 12/10/2010
wwang : 8/20/2010
ckniffin : 8/19/2010