title: The first COL7A1 mutation survey in a large Spanish dystrophic epidermolysis bullosa cohort: c.6527insC disclosed as an unusually recurrent mutation.
abstract: BACKGROUND
  Dystrophic epidermolysis bullosa (DEB) is a genodermatosis caused by mutations in COL7A1. The clinical manifestations are highly variable from nail dystrophy to life-threatening blistering, making early molecular diagnosis and prognosis of utmost importance for the affected families. Mutation identification is mandatory for prenatal testing.
  
  
  OBJECTIVE
  To conduct the first mutational analysis of COL7A1 in a Spanish cohort, to assess mutation consequences at protein/mRNA level and to establish genotype-phenotype correlations.
  
  
  METHODS
  Forty-nine Spanish patients with DEB were studied. Antigen mapping was performed on patient skin biopsies. COL7A1 mutation screening in genomic DNA was performed by polymerase chain reaction (PCR) and direct sequencing. Mutation consequences were determined by reverse transcriptase-PCR.
  
  
  RESULTS
  Eight patients belonged to three unrelated families with dominant DEB. Forty-one were affected with recessive DEB (RDEB). Specifically, 27 displayed the severe generalized subtype, eight the other generalized subtype and six a localized phenotype (two pretibial, three acral and one inversa). Thirty-five mutations were identified, 20 of which are novel. The pathogenic mutation c.6527insC accounted for 46.3% of Spanish RDEB alleles. A consistent genotype-phenotype correlation was established.
  
  
  CONCLUSIONS
  Although the COL7A1 database indicates that most DEB mutations are family specific, the pathogenic mutation c.6527insC was highly recurrent in our cohort. This level of recurrence for a single genetic defect has never previously been reported for COL7A1. Our findings are essential to the clinicians caring for patients with DEB in Spain and in the large population of Spanish descendants in Latin America. They also provide geneticists a molecular clue for a priority mutation screening strategy.
authors.affiliation: Basic Research Department, Epithelial Biomedicine Division, Regenerative Medicine Unit, CIEMAT-CIBERER U714, Av. Complutense 22, 28040 Madrid, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Escámez
authors.forename: M
authors.initials: M
authors.lastname: García
authors.forename: N
authors.initials: N
authors.lastname: Cuadrado-Corrales
authors.forename: S G
authors.initials: SG
authors.lastname: Llames
authors.forename: A
authors.initials: A
authors.lastname: Charlesworth
authors.forename: N
authors.initials: N
authors.lastname: De Luca
authors.forename: N
authors.initials: N
authors.lastname: Illera
authors.forename: C
authors.initials: C
authors.lastname: Sánchez-Jimeno
authors.forename: A
authors.initials: A
authors.lastname: Holguín
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authors.initials: B
authors.lastname: Duarte
authors.forename: M J
authors.initials: MJ
authors.lastname: Trujillo-Tiebas
authors.forename: J L
authors.initials: JL
authors.lastname: Vicario
authors.forename: J L
authors.initials: JL
authors.lastname: Santiago
authors.forename: A
authors.initials: A
authors.lastname: Hernández-Martín
authors.forename: A
authors.initials: A
authors.lastname: Torrelo
authors.forename: D
authors.initials: D
authors.lastname: Castiglia
authors.forename: C
authors.initials: C
authors.lastname: Ayuso
authors.forename: F
authors.initials: F
authors.lastname: Larcher
authors.forename: J L
authors.initials: JL
authors.lastname: Jorcano
authors.forename: A
authors.initials: A
authors.lastname: Meana
authors.forename: G
authors.initials: G
authors.lastname: Meneguzzi
authors.forename: G
authors.initials: G
authors.lastname: Zambruno
authors.forename: M
authors.initials: M
authors.lastname: Del Rio
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D024143:Collagen Type VII / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D013030:Spain; D055815:Young Adult
chemical_list: D024143:Collagen Type VII