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Prenatal diagnosis of Ullrich congenital muscular dystrophy using haplotype analysis and collagen VI immunocytochemistry
Author(s) -
Brockington Martin,
Brown Susan C.,
Lampe Anne,
Yuva Yeliz,
Feng Lucy,
JimenezMallebrera Cecilia,
Sewry Caroline A.,
Flanigan Kevin M.,
Bushby Kate,
Muntoni Francesco
Publication year - 2004
Publication title -
prenatal diagnosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.956
H-Index - 97
eISSN - 1097-0223
pISSN - 0197-3851
DOI - 10.1002/pd.902
Subject(s) - collagen vi , proband , haplotype , prenatal diagnosis , chorionic villus sampling , pathology , fetus , amniocentesis , medicine , genetics , biology , pregnancy , mutation , extracellular matrix , gene , genotype
Objectives 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. Conclusion 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. Copyright © 2004 John Wiley & Sons, Ltd.