A homozygous nonsense mutation in the alpha 3 chain gene of laminin 5 (LAMA3) in Herlitz junctional epidermolysis bullosa: prenatal exclusion in a fetus at risk.
Mutations in the three genes (LAMA3, LAMB3, and LAMC2) that encode the three chains (alpha 3, beta 3, and gamma 2, respectively) of laminin 5, a protein involved in epidermal-dermal adhesion, have been established as the genetic basis for the inherited blistering skin disorder, Herlitz junctional epidermolysis bullosa (H-JEB). In this study, we performed mutational analysis on genomic DNA from a child with H-JEB and identified a nonsense mutation in the alpha 3 chain gene (LAMA3) consisting of a homozygous C-to-T transition resulting in a premature termination codon (CGA-->TGA) on both alleles. The parents were shown to be heterozygous carriers of the same mutation. Direct mutation analysis was used to perform DNA-based prenatal diagnosis from a chorionic villus biopsy at 10 weeks' gestation in a subsequent pregnancy. The fetus was predicted to be genotypically normal with respect to the LAMA3 mutation.
McGrath
J A
JA
Department of Dermatology, Jefferson Medical College, Philadelphia, PA 19107, USA.
Kivirikko
S
S
Ciatti
S
S
Moss
C
C
Dunnill
G S
GS
Eady
R A
RA
Rodeck
C H
CH
Christiano
A M
AM
Uitto
J
J
D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002648:Child; D015193:Chorionic Villi Sampling; D004252:DNA Mutational Analysis; D017931:DNA Primers; D016109:Epidermolysis Bullosa, Junctional / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D046911:Macromolecular Substances; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011296:Prenatal Diagnosis; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D017931:DNA Primers; D046911:Macromolecular Substances; D000097794:Kalinin