T. Geddedahl et al., JUNCTIONAL EPIDERMOLYSIS-BULLOSA INVERSA (LOCUS EBR2A) ASSIGNED TO 1Q31 BY LINKAGE AND ASSOCIATION TO LAMC1, Human molecular genetics, 3(8), 1994, pp. 1387-1391
Junctional epidermolysis bullosa inversa is an autosomal recessive bli
stering skin disease with an ultrastructural hemidesmosome defect simi
lar to that of the Herlitz disease, yet with a non-lethal and differen
t course of the disease. Its delineation is based on five geographical
ly associated Norwegian families where all parents are likely to carry
a mutant EBR2A allele identical in descent. Three informative familie
s show a lod score of +1.65 at zero recombination to a trinucleotide r
epeat marker in intron 20 of the laminin gamma 1 (LAMC1, previously LA
MBP) locus on 1q31. The four patients of these families are all homozy
gous for the 146 bp LAMC1 allele present only on 5% of random Norwegia
n chromosomes. The daughter of a deceased patient in a fourth family c
arries the same 146 bp allele. This extreme association confirms that
the disease locus, EBR2A, is at or closely linked to LAMC1. Localized
and generalized Mitis types as well as the majority of tested families
with the Herlitz type of junctional epidermolysis bullosa appeared no
t to be similarly linked or associated to LAMC1. The Mspl and Alul RFL
Ps of LAMC1 showed absolute allelic association. Each of the two RFLP
haplotypes showed association to either 'long' or 'short' intron 20 ST
R alleles.