Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.22.54 (
calpain 3
)
430
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We report on two siblings with late-onset, limb-girdle muscular dystrophy (LGMD) inherited in an autosomal recessive manner. The LGMD was characterized by many rimmed vacuoles and reduced expression of the laminin beta1 chain in skeletal muscle. Both patients developed a progressive wasting and weakness of limb-girdle muscles in the late forties or early fifties; their facial, ocular, bulbar, and cardiac muscles were not involved. Histopathology of skeletal muscles biopsies showed typical dystrophic changes with many rimmed vacuoles. The immunoreactivity of the laminin beta1 chain was reduced in the muscle fibers, while dystrophin, sarcoglycans, beta-dystroglycan, dysferlin, and other laminin components were normally expressed. A mutation search revealed that no mutation existed in the coding region of the
calpain 3
, telethonin and UDP-N-acetylglucosamine 2-epimerase/N-acetylmanosamine kinase (
GNE
) genes. We conclude that this autosomal recessive LGMD is unknown and characterized by its late onset, rimmed vacuoles and reduction of the laminin beta1 chain in muscle fibers.
...
PMID:Late-onset autosomal recessive limb-girdle muscular dystrophy with rimmed vacuoles. 1500 3
Inherited muscular disorders (IMDs) are clinically and genetically heterogeneous genetic disorders. We investigated the mutational spectrum and genotype-phenotype correlations in Korean patients with IMD. We developed a targeted panel of 69 known IMD genes and recruited a total of 209 Korean patients with IMD. Targeted capture sequencing identified 994 different variants. Among them, 98 variants were classified as pathogenic/likely pathogenic variants; 38 were novel variations. A total of 39 patients had the pathogenic/likely pathogenic variants. Among them, 75 (36%) patients were genetically confirmed, and 18 (9%) patients had one heterozygous variant of recessive myopathy. However, two genetically confirmed patients had an additional heterozygous variant of another recessive myopathy. Four patients with one heterozygous variant of a recessive myopathy showed different phenotypes, compared with the known phenotype of the identified gene. The major causative genes of Korean patients with IMDs were DMD (19 patients), COL6A1 (9), DYSF (9),
GNE
(7), LMNA (7),
CAPN3
(6), and RYR1 (5). This study showed the mutational and clinical spectra in Korean patients with IMD and confirmed the usefulness of strategies utilizing targeted sequencing.
...
PMID:Discovery of pathogenic variants in a large Korean cohort of inherited muscular disorders. 2736 42
Objective:
Inherited myopathies comprise more than 200 different individually rare disease-subtypes, but when combined together they have a high prevalence of 1 in 6,000 individuals across the world. Our goal was to determine for the first time the clinical- and gene-variant spectrum of genetic myopathies in a substantial cohort study of the Indian subcontinent.
Methods:
In this cohort study, we performed the first large clinical exome sequencing (ES) study with phenotype correlation on 207 clinically well-characterized inherited myopathy-suspected patients from the Indian subcontinent with diverse ethnicities.
Results:
Clinical-correlation driven definitive molecular diagnosis was established in 49% (101 cases; 95% CI, 42-56%) of patients with the major contributing pathogenicity in either of three genes,
GNE
(28%;
GNE
-myopathy),
DYSF
(25%; Dysferlinopathy), and
CAPN3
(19%; Calpainopathy). We identified 65 variant alleles comprising 37 unique variants in these three major genes. Seventy-eight percent of the
DYSF
patients were homozygous for the detected pathogenic variant, suggesting the need for carrier-testing for autosomal-recessive disorders like Dysferlinopathy that are common in India. We describe the observed clinical spectrum of myopathies including uncommon and rare subtypes in India: Sarcoglycanopathies (
SGCA/B/D/G
), Collagenopathy (
COL6A1/2/3
), Anoctaminopathy (
ANO5
), telethoninopathy (
TCAP
), Pompe-disease (
GAA
), Myoadenylate-deaminase-deficiency-myopathy (
AMPD1
), myotilinopathy (
MYOT
), laminopathy (
LMNA
), HSP40-proteinopathy (
DNAJB6
), Emery-Dreifuss-muscular-dystrophy (
EMD
), Filaminopathy (
FLNC
), TRIM32-proteinopathy (
TRIM32
), POMT1-proteinopathy (
POMT1
), and Merosin-deficiency-congenital-muscular-dystrophy-type-1 (
LAMA2
). Thirteen patients harbored pathogenic variants in >1 gene and had unusual clinical features suggesting a possible role of synergistic-heterozygosity/digenic-contribution to disease presentation and progression.
Conclusions:
Application of clinically correlated ES to myopathy diagnosis has improved our understanding of the clinical and genetic spectrum of different subtypes and their overlaps in Indian patients. This, in turn, will enhance the global gene-variant-disease databases by including data from developing countries/continents for more efficient clinically driven molecular diagnostics.
...
PMID:Clinical and Genomic Evaluation of 207 Genetic Myopathies in the Indian Subcontinent. 3325 Aug 42
