Rothmund‐Thomson syndrome (RTS) is an autosomal recessive disorder characterized by skin abnormalities that appear in infancy, skeletal abnormalities, juvenile cataracts and other manifestations of premature aging, and a predisposition to malignancy. The diagnosis is made on clinical grounds as no consistent laboratory test has been identified. Chromosome studies have been reported for only three patients with RTS and in two of these three, trisomy 8 mosaicism was found. We performed a variety of cytogenetic and molecular genetic studies on two siblings with RTS and on their phenotypically normal parents. Two chromosomally abnormal clones involving either trisomy 8 or i(8q) were found in both patients with RTS. These clones were present in vivo, as they were seen in interphase buccal smears and lymphocytes from unstimulated preparations using both conventional cytogenetic studies and fluorescence in situ hybridization (FISH) with a centromere probe for chromosome 8. These results suggest that RTS is associated with in vivo clonal chromosomal rearrangements causing an acquired somatic mosaicism.

Familial hemophagocytic lymphohistiocytosis (FHLH) is an autosomal recessive disease with features similar to those of the murine motheaten phenotype resulting from mutations of protein tyrosine phosphatase SHP-1. This has raised the possibility that defects in SHP-1 or SHP-1-regulated signaling molecules may be present in FHLH. In this study, we examined SHP-1 protein and transcript in the peripheral blood mononuclear cells (PBMC) of an FHLH family. Our results show that the FHLH patient and the parents express comparable levels of a single SHP-1 protein and that the SHP-1 cDNA clone from the patient contains no mutation in the coding region. Interestingly, a reduced association of SHP-1 with the Jak family kinase Tyk2 was detected in the patient and the defect appears to have been inherited from one of the parents. This reduced SHP-1/Tyk2 association is likely due to a defect in Tyk2 or in cellular factors regulating Tyk2, because we found no abnormalities in SHP-1 or in SHP-1 association with the other Jak kinases. These data demonstrate that the SHP-1 gene is intact in FHLH and that the defect in some cases with this disease may involve signaling molecules regulated by SHP-1.

Radiological studiesFig. 1. Anteroposterior roentgenogram of right knee and proximal tibia showing a sclerotic and lytic destructive lesionFig. 2. Anteroposterior roentgenogram of proximal end of the right humerus shows a sclerotic destructive lesion Fig. 3. Anteroposterior roentgenogram of left ankle shows a sclerotic lesion of the distal end of the fibula Clinical informationA 15-year-old girl with a 3-month history of pain in her right knee was first seen in June 1990. Clinical examination revealed a soft-tissue mass over the medial aspect of the proximal end of the tibia. She was short of stature and had atrophic skin changes with hyperpigmentation and aplastic thumbs.Roentgenograms showed a destructive lesion in the proximal area of the right tibia, with a mixed sclerotic and lytic appearance (Fig. 1). The results of a chest roentgenogram and computed tomography (CT) scan of the lungs were normal. However, a bone scan showed increased uptake in the proximal area of the right humerus and the distal end of the left fibula. Roentgenograms showed a destructive sclerotic lesion in the proximal area of the right humerus and the distal end of the left fibula (Figs. 2, 3). A biopsy of the right proximal tibial lesion was performed.

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