1. ^*Department of Dermatology and Cutaneous Biology, Jefferson Medical College, and The Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A.
2. ^†Department of Dermatology, Keio University School of Medicine, Tokyo, Japan
3. ^‡Department of Pediatrics, Sano Kose General Hospital, Sano, Japan

Correspondence: Dr Jouni Uitto, Department of Dermatology and Cutaneous Biology, Jefferson Medical College, 233 S. 10th Street, Suite 450 BLSB, Philadelphia, PA 10107

¹Permanent address: Division of Diagnostic Services, Chromosome and DNA Laboratory, Kuopio University Hospital, Kuopio, Finland.

Received 8 November 1997; Revised 30 December 1997; Accepted 20 January 1998.

Abstract

Herlitz junctional epidermolysis bullosa (OMIM#226700) is a lethal, autosomal recessive blistering disorder caused by mutations in one of the three genes LAMA3, LAMB3, or LAMC2, encoding the constitutive polypeptide subunits of laminin 5. In this study, we describe a patient homozygous for a novel nonsense mutation Q936X in exon 19 of LAMB3, which has been mapped to chromosome 1q32. The patient was born with extensive blistering and demonstrated negative immunofluorescence staining for laminin 5, and transmission electron microscopy revealed tissue separation within lamina lucida of the dermal–epidermal junction, diagnostic of Herlitz junctional epidermolysis bullosa. The mother of the proband was found to be a heterozygous carrier for this mutation, whereas the father demonstrated the wild-type LAMB3 allele only. Nonpaternity was excluded by 13 microsatellite markers in six different chromosomes. Genotype analysis using 28 microsatellite markers spanning chromosome 1 revealed that the patient had maternal primary heterodisomy, as well as meroisodisomy within two regions of chromosome 1, one on 1p and the other one on 1q, the latter region containing the maternal LAMB3 mutation. These results suggest that Herlitz junctional epidermolysis bullosa in this patient developed as a result of reduction to homozygosity of the maternal LAMB3 mutation on chromosome 1q32.