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Greig cephalopolysyndactyly (GCPS) (OMIM 175700) is an autosomal dominant disorder characterized by a distinct combination of craniofacial, hand and foot malformations. In this report, clinical and radiological findings of 12 patients with GCPS derived from 4 independent families and 3 sporadic cases with documented GLI3 mutations are presented with particular emphasis on inter- and intrafamilial variability. In a particularly instructive family in which 9 members of 4 generations could be studied clinically and molecularly, a missense mutation (R625W) is transmitted and shows a partially penetrant pattern. In a branch of the family, the GCPS phenotype skips a generation via a normal female carrier without clinical signs providing evidence that GCPS does not always manifest full penetrance as generally supposed. © 2003 Wiley-Liss, Inc.

We describe a three-generation family with clinical and radiological findings of osteopoikilosis in five and melorheostosis in one individual. The co-occurrence of both rare bone disorders suggests that both conditions might be related as suggested previously by Butkus et al. [1997: Am J Med Genet 72:43–46] and Nevin et al. [1999: Am J Med Genet 82:409–414]. The findings in this family strengthen the hypothesis that osteopoikilosis is an autosomal dominant condition and that an early postzygotic second hit mutation in the second allele results in melorheostosis. © 2003 Wiley-Liss, Inc.

The precise etiology of hydronephrosis caused by pelvi-ureteric junction obstruction is not yet known but there is convincing evidence for a genetic cause, with linkage analysis predicting a hereditary hydronephrosis locus on chromosome 6p. In previous studies, a patient was described with ade novoautosomal t(6;19)(p21;q13.1) translocation and suffering from bilateral multicystic renal dysplasia (MRD) caused by a bilateral complete pelvi-ureteric junction obstruction. In an effort to elucidate a possible correlation between this translocation and hereditary hydronephrosis, we have carried out an extensive molecular characterization of a chromosome 19 cosmid clone previously identified as spanning the translocation in this unique index case. DNA sequencing across a 9.2-kbBamHI fragment that straddles the translocation indicates the presence of DNA sequences with a high degree of similarity to theUSF2gene that encodes the transcription factor USF2 (upstream stimulator factor 2). The genomic structure ofUSF2consists of 10 exons distributed over a DNA region of about 11 kb. The putative promoter region is GC-rich and lacks TATA and CCAAT boxes, suggesting that expression of theUSF2gene may be controlled by a typical housekeeping gene promoter. The chromosome 19 breakpoint in the MRD patient appeared to have occurred in intron 7 of theUSF2gene. Northern blot analysis of a variety of human tissues revealed that theUSF2gene is ubiquitously expressed. Furthermore, Northern blot and 3′-RACE analysis of mRNA isolated from lung fibroblasts of the MRD patient failed to detect a fusion transcript involvingUSF2sequences, suggesting gene disruption rather than the generation of a fusion gene as a possible underlying mechanism.

We describe an 8-year-old girl who developed a posttraumatic pseudarthrosis of the right clavicle. Despite the great periosteal regenerative potential in children, the fracture did not heal at 12 months with a classic conservative treatment. As a result of pain and functional limitations, surgical treatment was required. Excess bone of the hypertrophic nonunion was removed and an open reduction and internal fixation with a compression plate were performed. Cancellous bone chips from the iliac crest were packed into the fracture site. Good remodelling and consolidation was achieved 10 months after the operation. At that stage, the functional outcome was satisfactory.

We describe two siblings with carpal and tarsal synostoses associated with transverse deficiencies of the toes. Mutation analysis of the NOG gene revealed a double missense mutation in both boys resulting in Pro42Ala and Pro50Arg. The parents were clinically unaffected, and these two mutations were not detected in their white blood cells or buccal mucosa. This indicates the presence of gonadal mosaicism or a low level of somatic mosaicism in one of the parents. © 2005 Wiley‐Liss, Inc.