We performed dentofacial examination of patients with CMD and evaluated consequences of orthodontic movement in a mouse model carrying a CMD knock-in (KI) mutation (Phe377del) in the Ank gene.
ANKH, the human homolog of the mutated gene in the ank/ank mouse, has been implicated in familial autosomal-dominant chondrocalcinosis and autosomal-dominant craniometaphyseal dysplasia.
To identify the rate of change of clinical outcome measures in children with 2 types of congenital muscular dystrophy (CMD), COL6-related dystrophies (COL6-RDs) and LAMA2-related dystrophies (LAMA2-RDs).
We have previously employed profiling techniques to elucidate molecular patterns and demonstrated significant metabolic impairment in skeletal muscle from LAMA2-CMD patients and mouse models.
Forty-one patients with CMD, either collagen 6 related disorders (COL6-RD; n = 21) or laminin α-2-related disorders (LAMA2-RD; n = 20), and 21 healthy pediatric controls underwent 2 yearly EIM exams.
Potential therapies are currently under development for two congenital muscular dystrophy (CMD) subtypes: collagen VI-related muscular dystrophy (COL6-RD) and laminin alpha 2-related dystrophy (LAMA2-RD).
In this study, we assessed 43 CMD patients with typical white matter abnormality and laminin-α2 deficiency (complete or partial) diagnosed by immunohistochemistry to determine the clinical and molecular genetic characteristics of laminin-α2 deficient CMD.
Molecular genetics revealed 2 pathogenic LAMA2 mutations in 5 of 18 CMD and 3 of 128 LGMD patients, corresponding to a LAMA2-mutation frequency of 28% in the CMD and 2.3% in the LGMD cohorts, respectively.
Mutation analysis revealed two distinct mutations: a c.8005delT frameshift deletion in exon 56 of the LAMA2 (laminin-α2) gene (MDC1A) was found in the CMD patient and a new homozygous mutation c.1536+1G>T in the donor splice site of intron 12 of the CAPN3 (calpain3) gene (LGMD2A) was found in the LGMD patients.
Deficiency of laminin alpha2 chain caused by mutations of the LAMA2 gene on chromosome 6q2 account for approximately 50% of cases of congenital muscular dystrophy (CMD) in white patients.
Approximately half the cases of classical congenital muscular dystrophy (CMD) have a pronounced deficiency or absence of the laminin alpha 2 chain of laminin-2 (merosin).
In the 'merosin-deficient' subgroup, which represents about half of the cases, more definite evidence of the involvement of the laminin alpha2-chain has recently been reported with the identification of mutations in the gene encoding the alpha2-chain of laminin 2 (LAMA2) in CMD patients.