Genomic changes within chromosome band 11p13 appear to have a role in the initiation of Wilms' tumour. The human Harvey ras oncogene, c-Ha-ras 1, has been located by Jhanwar et al. immediately adjacent to this region at band 11p14 .1, although several groups have assigned the gene more distally at band 11p15 . We have examined tumour DNA from two cases of sporadic Wilms' tumour, and report here that in both cases one of the two constitutional c-Ha-ras 1 alleles was absent. One tumour had a reciprocal translocation between the short arm of chromosome 11 (at band 11p13), and the long arm of chromosome 12, with no visible loss of chromosomal material. The loss of a c-Ha-ras 1 allele in association with this translocation indicates that a submicroscopic deletion had occurred. The resulting hemizygosity may have had a role in tumour initiation. Our results indicate that the c-Ha-ras 1 gene and the 'Wilms' tumour locus' may be in close proximity. It would, therefore, be premature to exclude the possibility that these two sites are functionally related.

Alleles↗

PubMedDate not supplied

Transient neonatal diabetes mellitus in a child with paternal uniparental disomy of chromosome 6.

We report a male infant with transient neonatal diabetes mellitus (TNDM; MIM 601410), macroglossia, hypertelorism, umbilical hernia, inguinoscrotal hernia and onychomycosis. Diabetes mellitus was diagnosed 10 days after birth and resolved after 6.5 months of treatment. Genetic investigation indicated the presence of paternal uniparental disomy of chromosome 6 (UPD 6). The finding of paternal UPD 6 allows prediction of a transient, rather than permanent NDM, and no increased recurrence risk of TNDM in subsequent pregnancies. Therefore, finding of NDM should be a strong indicator for genetic testing.

Blood Glucose↗

PubMedDate not supplied

Central precocious puberty in a girl with triple X syndrome and neonatal diabetes mellitus associated with paternal isodisomy of chromosome 6.

We describe a girl with triple X syndrome and paternal isodisomy of chromosome 6 (UPD6), who developed neonatal diabetes mellitus (NDM) and precocious puberty. At birth she presented growth retardation and congenital anomalies (ventricular septal defect, macroglossia, umbilical hernia). Diabetes mellitus (DM) was diagnosed at 31 days of life and treated with insulin for 13 months. DM recurred at 4 years of age and since that time it required insulin, in spite of preserved beta-cell function. Tall stature was present from early childhood. At 7 years of age the girl presented central precocious puberty, height velocity further increased, but her near-final height was normal. This patient is unique in that precocious puberty has never been described in triple X females. Moreover it is a further example of paternal UPD6 causing NDM with a predisposition to type 2 DM in later life.

DNA↗