A founder COL17A1 splice site mutation leading to generalized atrophic benign epidermolysis bullosa in an extended inbred Palestinian family from Israel.
OBJECTIVE
Generalized atrophic benign epidermolysis bullosa is a nonlethal form of junctional EB with an autosomal recessive inheritance. There is generalized cutaneous blister formation at sites of trauma, atrophic alopecia affecting scalp, eyelash and eyebrow, dystrophic nail changes, and tooth abnormalities. In this study, we have studied a five-generation Palestinian family affected with generalized atrophic benign epidermolysis bullosa.


METHODS
We have performed linkage analysis to genes that are mutated in generalized atrophic benign epidermolysis bullosa, followed by direct sequencing of patient genomic DNA.


RESULTS
We have shown that the disease is caused by a newly detected homozygous donor splice site mutation, IVS51+1G>A, in the type XVII collagen gene, COL17A1.


CONCLUSIONS
The effect of a founder mutation introduced 3 to 4 generations before a disease appearance is demonstrated in this inbred family.
Whittock
Neil Vincent
NV
Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom.
Sher
Carron
C
Gold
Isaac
I
Libman
Vitalia
V
Reish
Orit
O
D001324:Autoantigens / Q000235:genetics*; D002352:Carrier Proteins; D003094:Collagen / Q000235:genetics*; D003241:Consanguinity; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D000071821:Dystonin; D016109:Epidermolysis Bullosa, Junctional / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D010375:Pedigree; D017422:Sequence Analysis, DNA; D000097805:Collagen Type XVII
D001324:Autoantigens; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D000071821:Dystonin; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII; C486268:DST protein, human