Congenital muscular dystrophy with integrin alpha 7 deficiency is an extremely rare autosomal recessive CMD that has been reported in only a few patients. Reported symptoms include proximal weakness, congenital torticollis, congenital hip dislocation, multiple joint contractures, and motor delays characteristic of a congenital myopathy. One patient was reported to have mental retardation without brain MRI changes.
Affected individuals have mildly elevated serum creatine kinase levels and immunohistochemistry can reveal absent integrin alpha 7 with normal laminin alpha 2 (merosin). Muscle biopsy is consistent with congenital myopathy. Mutations in the ITGA7 gene (12q13), including deletions, splice-site mutations, and missense mutations, have been found in affected individuals.
For patients with suspected CMD with integrin alpha 7 deficiency, sequence analysis is recommended as the first step in mutation identification. For patients in whom mutations are not identified by full gene sequencing, deletion/duplication analysis is appropriate.
- Bonnemann, Carsten. Personal communication. July 8, 2009.
- Conti Reed, U. Congenital muscular dystrophy part I: A review of phenotypical and diagnostic aspects. Arq Neuropsiquiatr. 2009; 67:144-168.
- GeneTests: Congenital Muscular Dystrophy Overview. http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene∂=cmd-overview
- Mendell, JR et al. The congenital muscular dystrophies: Recent advances and molecular insights. Ped and Dev Pathology. 2006; 9:427-443.
This test is indicated for:
- Confirmation of a clinical diagnosis of CMD with integrin alpha 7 deficiency
- Carrier testing in adults with a family history of CMD with integrin alpha 7 deficiency
Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient's biochemical phenotype.
Analytical Sensitivity: ~99%
Orangene™ Saliva Collection Kit used according to manufacturer instructions. Please contact EGL for a Saliva Collection Kit for patients that cannot provide a blood sample.
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Submit copies of diagnostic biochemical test results with the sample, if appropriate. Contact the laboratory if further information is needed.
Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of EGL Genetics, please submit a copy of the sequencing report with the test requisition.
- Deletion/duplication analysis of the ITGA7 gene by CGH array is available for those individuals in whom sequence analysis is negative.
- Familial mutation testing is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.
- Prenatal testing is available to couples who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.