Biomedical subjects

David O Sillence

Publications and source records attributed to David O Sillence.

4 recordsLinked to original sources

PubMed2006

Neonatal severe hyperparathyroidism: an important clue to the aetiology.

Neonatal severe hyperparathyroidism is a rare condition that presents as striking hyperparathyroidism, hypercalcaemia, and metabolic bone disease. The aetiology needs to be determined soon after diagnosis to direct appropriate management and to determine an accurate prognosis. Taking a family history is a valuable clinical tool in paediatric medicine. Presented here is the case of a neonate presenting with severe hyperparathyroidism. Obtaining the family history, coupled with basic parental studies, enabled a rapid aetiological diagnosis, which allowed for conservative management.

Birth Weight↗

PubMed2005

Three patients with terminal deletions within the subtelomeric region of chromosome 9q.

We report on three male infants with de novo terminal deletions of chromosome 9q34.3. The clinical features are compared to the nine cases described in the literature. Case 1 and 3 were ascertained following the use of subtelomeric FISH to screen for a chromosomal anomaly, case 2 was confirmed by FISH probe following detection of a 9q deletion on standard karyotyping. Deletions in this region result in severe developmental delay, a distinct facial phenotype, cardiac anomalies, obesity, and respiratory failure, which may result in premature death. The delineation of the 9q deletion phenotype will aid diagnosis and genetic counseling as subtelomere FISH screening becomes more widely available.

Abnormalities, Multiple↗

PubMed2003

Identification of PLOD2 as telopeptide lysyl hydroxylase, an important enzyme in fibrosis.

The hallmark of fibrotic processes is an excessive accumulation of collagen. The deposited collagen shows an increase in pyridinoline cross-links, which are derived from hydroxylated lysine residues within the telopeptides. This change in cross-linking is related to irreversible accumulation of collagen in fibrotic tissues. The increase in pyridinoline cross-links is likely to be the result of increased activity of the enzyme responsible for the hydroxylation of the telopeptides (telopeptide lysyl hydroxylase, or TLH). Although the existence of TLH has been postulated, the gene encoding TLH has not been identified. By analyzing the genetic defect of Bruck syndrome, which is characterized by a pyridinoline deficiency in bone collagen, we found two missense mutations in exon 17 of PLOD2, thereby identifying PLOD2 as a putative TLH gene. Subsequently, we investigated fibroblasts derived from fibrotic skin of systemic sclerosis (SSc) patients and found that PLOD2 mRNA is highly increased indeed. Furthermore, increased pyridinoline cross-link levels were found in the matrix deposited by SSc fibroblasts, demonstrating a clear link between mRNA levels of the putative TLH gene (PLOD2) and the hydroxylation of lysine residues within the telopeptides. These data underscore the significance of PLOD2 in fibrotic processes.

Amino Acid Sequence↗

PubMed2002

Gracile bone dysplasias.

Gracile bone dysplasias constitute a group of disorders characterised by extremely slender bones with or without fractures. We report four newborns, two of whom showed multiple fractures. Two babies had osteocraniostenosis and one had features of oligohydramnios sequence. The diagnosis in the fourth newborn, which showed thin long bones and clavicles and extremely thin, poorly ossified ribs, is uncertain. Exact diagnosis of a gracile bone dysplasia is important for genetic counselling and medico-legal reasons.

Bone Diseases, Developmental↗