The first COL7A1 mutation survey in a large Spanish dystrophic epidermolysis bullosa cohort: c.6527insC disclosed as an unusually recurrent mutation.
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.
Escámez
M J
MJ
Basic Research Department, Epithelial Biomedicine Division, Regenerative Medicine Unit, CIEMAT-CIBERER U714, Av. Complutense 22, 28040 Madrid, Spain.
García
M
M
Cuadrado-Corrales
N
N
Llames
S G
SG
Charlesworth
A
A
De Luca
N
N
Illera
N
N
Sánchez-Jimeno
C
C
Holguín
A
A
Duarte
B
B
Trujillo-Tiebas
M J
MJ
Vicario
J L
JL
Santiago
J L
JL
Hernández-Martín
A
A
Torrelo
A
A
Castiglia
D
D
Ayuso
C
C
Larcher
F
F
Jorcano
J L
JL
Meana
A
A
Meneguzzi
G
G
Zambruno
G
G
Del Rio
M
M
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
D024143:Collagen Type VII