title: Prenatal diagnosis of Ullrich congenital muscular dystrophy using haplotype analysis and collagen VI immunocytochemistry.
abstract: OBJECTIVE
  Ullrich congenital muscular dystrophy (UCMD) is a recessively inherited condition characterised by proximal joint contractures, marked distal joint hyperextensibility, rigidity of the spine and early respiratory failure. Recently, mutations in the genes encoding the subunits of collagen VI have been identified in this disease. We undertook two prenatal diagnoses for UCMD in a consanguineous family where the disease was consistent with linkage to the COL6A3 locus and immunolabelling of collagen VI in the proband's skeletal muscle was severely reduced.
  
  
  METHODS
  Both haplotype analysis and collagen VI immunolabelling were used to determine the status of the fetuses.
  
  
  RESULTS
  Haplotype analysis of DNA extracted from chorionic villus samples (CVS) from the initial at-risk pregnancy with markers encompassing COL6A3 demonstrated that this fetus had inherited the same haplotypes as the affected child, and immunolabelling of the at-risk CVS demonstrated the virtual absence of collagen VI. A second latter fetus inherited neither of the at-risk haplotypes and collagen VI expression in the CVS was normal. During the second pregnancy, a homozygous G > A change in the last nucleotide of exon 27 of COL6A3 was identified in the proband, substantiating the results obtained from haplotype analysis and collagen VI immunolabelling.
  
  
  CONCLUSIONS
  These findings demonstrate that haplotype analysis in combination with immunocytochemistry is a rapid and reliable method for prenatal diagnosis of UCMD, provided the family is genetically informative and reduced collagen VI expression in the proband has been demonstrated.
authors.affiliation: Dubowitz Neuromuscular Centre, Department of Pediatrics, Hammersmith Hospital, Imperial College London, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Brockington
authors.forename: Susan C
authors.initials: SC
authors.lastname: Brown
authors.forename: Anne
authors.initials: A
authors.lastname: Lampe
authors.forename: Yeliz
authors.initials: Y
authors.lastname: Yuva
authors.forename: Lucy
authors.initials: L
authors.lastname: Feng
authors.forename: Cecilia
authors.initials: C
authors.lastname: Jimenez-Mallebrera
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sewry
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Flanigan
authors.forename: Kate
authors.initials: K
authors.lastname: Bushby
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D015193:Chorionic Villi Sampling; D024142:Collagen Type VI / Q000032:analysis* / Q000235:genetics*; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D007150:Immunohistochemistry; D018482:Muscle, Skeletal / Q000737:chemistry*; D009136:Muscular Dystrophies / Q000235:genetics*; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*
chemical_list: D024142:Collagen Type VI