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S Verhoef

Publications and source records attributed to S Verhoef.

24 records · Page 2Linked to original sources
PubMed1997

Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the widespread development of distinctive tumors termed hamartomas. TSC-determining loci have been mapped to chromosomes 9q34 (TSC1) and 16p13 (TSC2). The TSC1 gene was identified from a 900-kilobase region containing at least 30 genes. The 8.6-kilobase TSC1 transcript is widely expressed and encodes a protein of 130 kilodaltons (hamartin) that has homology to a putative yeast protein of unknown function. Thirty-two distinct mutations were identified in TSC1, 30 of which were truncating, and a single mutation (2105delAAAG) was seen in six apparently unrelated patients. In one of these six, a somatic mutation in the wild-type allele was found in a TSC-associated renal carcinoma, which suggests that hamartin acts as a tumor suppressor.

Amino Acid Sequence↗
PubMed1996

Identification of a nonsense mutation at the 5' end of the TSC2 gene in a family with a presumptive diagnosis of tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited disease with a high mutation rate. It is clinically a very variable disorder and hamartomas can occur in many different organs. TSC shows genetic heterogeneity; one gene, TSC1, is on chromosome 9q34, and the second gene, TSC2, on chromosome 16p13.3. Clinical criteria for diagnosis have been established, but diagnosis of patients with minimal expression of the disease can be very difficult. In children the phenotype is often incomplete or not fully assessable. Hence mildly affected subjects, at risk for severely affected offspring, may remain undiagnosed. The detection of (small) mutations in the tuberous sclerosis gene located on chromosome 16 (TSC2) has recently become possible and may be helpful in the diagnosis of ambiguous cases. To our knowledge, this is the first report of a point mutation in the TSC2 gene in a familial case of tuberous sclerosis. A nonsense mutation was detected in a family in which the father had only minor signs hinting at tuberous sclerosis. The son had multiple cardiac tumours and white patches, but full clinical investigation was impossible in this child. This case illustrates that mutation analysis can contribute to a diagnosis of tuberous sclerosis in families with an incomplete phenotype.

Adult↗
PubMed1994

Refined localization of TSC1 by combined analysis of 9q34 and 16p13 data in 14 tuberous sclerosis families.

Tuberous sclerosis (TSC) is a heterogeneous trait. Since 1990, linkage studies have yielded putative TSC loci on chromosomes 9, 11, 12 and 16. Our current analysis, performed on 14 Dutch and British families, reveals only evidence for loci on chromosome 9q34 (TSC1) and chromosome 16p13 (TSC2). We have found no indication for a third locus for TSC, linked or unlinked to either of these chromosomal regions. The majority of our families shows linkage to chromosome 9. We have refined the candidate region for TSC1 to a region of approximately 5 cM between ABL and ABO.

Chromosome Mapping↗
PubMed1994

The evolution of renal angiomyolipomas in patients with tuberous sclerosis.

In 1986, 23 patients with renal angiomyolipomas as part of tuberous sclerosis were assessed by ultrasonography. In 1991, 20 patients in this group were reexamined with special attention paid to the renal pathological condition. Ultrasonography was performed by the same radiologist who performed the examination in 1986. Of 20 patients 7 had severe hemorrhage necessitating hospital admission (5 had a renal lesion larger than 3.5 cm. in diameter). In 2 patients the exact diameter of the renal angiomyolipomas could not be determined and they underwent nephrectomy. Three patients underwent successful selective embolization of the bleeding angiomyolipoma. One patient died. The hemorrhage resolved spontaneously in 1 patient and treatment was not feasible. In 4 patients the lesions increased in size between 1986 and 1991. Based on these results there is a relationship between the size of the angiomyolipomas and the risk of bleeding. Renal angiomyolipomas larger than 3.5 cm. in diameter have a substantial risk for severe hemorrhage. Some angiomyolipomas show progression. Periodic followup is mandatory every 6 months. For angiomyolipomas larger than 3.5 cm. in diameter an aggressive approach is advised. Selective embolization is the initial method of choice.

Adult↗