Of 226 consecutive papillary carcinoma patients, 14 indicated that at least one other relative was similarly affected. Pathology confirmation was obtained in 8 of the 14 families. Of the eight families with documented familial papillary carcinoma, one had five members, another had four members, and yet another had three members affected. The remaining families had two members affected. In those families with two or more persons with confirmed papillary carcinomas of the thyroid, 20 first- and second-degree relatives were examined. Of those, one had a previously unidentified papillary carcinoma and 6 had a benign thyroid disease (4 primary hypothyroidism and 2 simple goiters). High-resolution chromosome studies of four patients from four different families were normal, and there was no increase in chromosome breakage in a fifth patient from yet another family. Autosomal dominant inheritance is possible. Although there was no family history of lipomas, osteomas, or intestinal polyposis to suggest Gardner syndrome, four parents of our familial papillary carcinoma patients had colon cancer. In addition, three other relatives died of unidentified intra-abdominal cancer. The apparently high frequency of colon cancer and other abdominal cancer in relatives was an additional concern. Based on our observations, three clinical recommendations can be made: obtain a family history of all patients with papillary carcinoma of the thyroid, since between 3.5 to 6.2% will have another affected relative; when two or more persons in a family have papillary carcinoma of the thyroid, all first- and second-degree relatives should have a neck palpation by an experienced examiner; and families with two or more persons with papillary carcinoma should be observed for possible colon cancer.

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Junctional epidermolysis bullosa (JEB) is an autosomal recessive disorder characterized by blister formation at the level of the lamina lucida within the cutaneous basement-membrane zone. Classic lethal JEB (Herlitz type [H-JEB]; OMIM 226700) is frequently associated with premature-termination-codon mutations in both alleles of one of the three genes (LAMA3, LAMC2, or LAMB3) encoding the subunit polypeptides (alpha3, beta3, and gamma2) of laminin 5. In this study, we describe a unique patient with H-JEB, who was homozygous for a nonsense mutation, Q243X, 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, whereas the father had two normal LAMB3 alleles. Nonpaternity was excluded by 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 uniparental meroisodisomy of a 35-cM region on 1q containing the maternal LAMB3 mutation and maternal uniparental heterodisomy of other regions of chromosome 1. Thus, the results suggested that reduction to homozygosity of the 1q region containing the maternal LAMB3 mutation caused the H-JEB phenotype. The patient was normally developed at term and did not show overt dysmorphisms or malformations. This is the first description of uniparental disomy of human chromosome 1.

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