title: Complete maternal isodisomy of chromosome 3 in a child with recessive dystrophic epidermolysis bullosa but no other phenotypic abnormalities.
abstract: The mechanobullous disease Hallopeau-Siemens recessive dystrophic epidermolysis bullosa (HS-RDEB) results from mutations in the type VII collagen gene (COL7A1) on chromosome 3p21.31. Typically, there are frameshift, splice site, or nonsense mutations on both alleles. In this report, we describe a patient with HS-RDEB, who was homozygous for a new frameshift mutation, 345insG, in exon 3 of COL7A1. However, sequencing of parental DNA showed that although the patient's mother was a heterozygous carrier of this mutation, the father's DNA contained only wild-type sequence. Microsatellite marker analysis confirmed paternity and genotyping of 28 microsatellites spanning chromosome 3 revealed that the affected child was homozygous for every marker tested with all alleles originating from a single maternal chromosome 3. Thus, the HS-RDEB phenotype in this patient is due to complete maternal isodisomy of chromosome 3 and reduction to homozygosity of the mutant COL7A1 gene locus. To our knowledge, there are no published reports of uniparental disomy (UPD) in HS-RDEB; moreover, this case represents only the third example of UPD of chromosome 3 to be reported. The severity of the HS-RDEB in this case was similar to other affected individuals and no additional phenotypic abnormalities were observed, suggesting an absence of maternally imprinted genes on chromosome 3.
authors.affiliation: Genetic Skin Disease Group, St John's Institute of Dermatology, King's College School of Medicine at Guy's, King's College and St Thomas' Hospitals, London, UK.
authors.forename: Hiva
authors.initials: H
authors.lastname: Fassihi
authors.forename: Liu
authors.initials: L
authors.lastname: Lu
authors.forename: Vesarat
authors.initials: V
authors.lastname: Wessagowit
authors.forename: Linda C
authors.initials: LC
authors.lastname: Ozoemena
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Jones
authors.forename: Patricia J C
authors.initials: PJ
authors.lastname: Dopping-Hepenstal
authors.forename: Lesley
authors.initials: L
authors.lastname: Foster
authors.forename: David J
authors.initials: DJ
authors.lastname: Atherton
authors.forename: Jemima E
authors.initials: JE
authors.lastname: Mellerio
authors.forename: John A
authors.initials: JA
authors.lastname: McGrath
mesh_terms: D000328:Adult; D001483:Base Sequence; D002893:Chromosomes, Human, Pair 3; D024143:Collagen Type VII / Q000235:genetics; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics* / Q000473:pathology*; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D010641:Phenotype; D024182:Uniparental Disomy
chemical_list: D024143:Collagen Type VII