title: Sarcoglycanopathies and the risk of undetected deletion alleles in diagnosis.
abstract: We have designed Multiplex Amplifiable Probe Hybridization (MAPH) probes for 28 exons of the sarcoglycan genes SGCA, SGCB, SGCG, and SGCD. The set was used to screen DNA from limb-girdle muscular dystrophy (LGMD) patients for the presence of pathogenic deletion or duplication mutations. An unexpected heterozygous deletion of SGCG exon 7 was detected in a patient from a consanguineous family in which a known c.525delT mutation segregates. The exon 7 deletion was inherited from the father, who was part of the consanguineous c.525delT branch of the family but who did not carry the c.525delT mutation. A similar, homozygous deletion had been identified in two unrelated LGMD patients from southern Italy. The deletion breakpoints were mapped, isolated, and sequenced, and were identical in all cases. Haplotype analysis showed the same alleles segregating with the mutation in all three patients, suggesting a common ancestor. Exonic deletions in sarcoglycanopathies appear to be rare events. However, we recommend screening for exonic deletions/duplications in patients where a mutation has not been identified in both alleles, as well as in seemingly homozygous cases where segregation of the mutations can not be confirmed in the parents.
authors.affiliation: Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: White
authors.forename: Shirley
authors.initials: S
authors.lastname: Uitte de Willige
authors.forename: Dennis
authors.initials: D
authors.lastname: Verbove
authors.forename: Luisa
authors.initials: L
authors.lastname: Politano
authors.forename: Ieke
authors.initials: I
authors.lastname: Ginjaar
authors.forename: Martijn H
authors.initials: MH
authors.lastname: Breuning
authors.forename: Johan T
authors.initials: JT
authors.lastname: den Dunnen
mesh_terms: D000483:Alleles; D001483:Base Sequence; D003241:Consanguinity; D005091:Exons / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D006239:Haplotypes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D016133:Polymerase Chain Reaction; D049031:Sarcoglycans / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D049031:Sarcoglycans