MATERNAL UNIPARENTAL DISOMY OF CHROMOSOME-1 WITH REDUCTION TO HOMOZYGOSITY OF THE LAMB3 LOCUS IN A PATIENT WITH HERLITZ JUNCTIONAL EPIDERMOLYSIS-BULLOSA

Junctional epidermolysis bullosa (JEB) is an autosomal recessive disor der characterized by blister formation at the level of the lamina luci da within the cutaneous basement-membrane zone. Classic lethal JEB (He rlitz type [H-JEB]; OMIM 226700) is frequently associated with prematu re-termination-codon mutations in both alleles of one of the three gen es (LAMA3, LAMC2, or LAMB3) encoding the subunit polypeptides (alpha 3 , beta 3, and gamma 2) of laminin 5. In this study, we describe a uniq ue patient with H-JEB, who was homozygous for a nonsense mutation, Q24 3X, in the LAMB3 gene on chromosome 1 and who had normal karyotype 46, XY. The mother was found to be a carrier of the Q243X mutation, wherea s the father had two normal LAMB3 alleles. Nonpaternity was excluded b y use of 11 microsatellite markers from six different chromosomes. The use of 17 partly or fully informative microsatellite markers spanning the entire chromosome 1 revealed that the patient had both maternal u niparental meroisodisomy of a 35-cM region on Iq containing the matern al LAMB3 mutation and maternal uniparental heterodisomy of other regio ns of chromosome 1. Thus, the results suggested that reduction to homo zygosity of the Iq region containing the maternal LAMB3 mutation cause d the H-JEB phenotype. The patient was normally developed at term and did not show overt dysmorphisms or malformations. This is the first de scription of uniparental disomy of human chromosome 1.