Biomedical subjects

V Wessagowit

Publications and source records attributed to V Wessagowit.

7 recordsLinked to original sources

PubMed2002

EEC (Ectrodactyly, Ectodermal dysplasia, Clefting) syndrome: heterozygous mutation in the p63 gene (R279H) and DNA-based prenatal diagnosis.

BACKGROUND: Germline mis-sense mutations in the DNA-binding domain of the p63 gene have recently been established as the molecular basis for the autosomal dominant EEC (Ectrodactyly, Ectodermal dysplasia, Clefting) syndrome. OBJECTIVES: To examine genomic DNA from a 36-year-old woman, her 58-year-old father and her 11-year-old son, all with the EEC syndrome, to determine the inherent p63 mutation and, after genetic counselling, to use knowledge of the mutation to undertake a first-trimester DNA-based prenatal diagnosis in a subsequent pregnancy. METHODS: Fetal DNA was extracted from chorionic villi and used to amplify exon 7 of p63 containing the potential mutation. Direct sequencing and restriction endonuclease digestion (loss of AciI site on mutant allele) were used for DNA-based prenatal diagnosis. RESULTS: We identified a heterozygous arginine to histidine p63 mutation, R279H, in all three affected individuals. Prenatal diagnosis demonstrated a homozygous wild-type sequence predicting an unaffected child: a healthy boy was subsequently born at full-term. CONCLUSIONS: These data expand the p63 gene mutation database and provide the first example of a DNA-based prenatal test in this ectodermal dysplasia syndrome.

Abnormalities, Multiple↗

PubMed2002

Dermatological applications of DNA array technology.

The Human Genome Project and other large scale sequencing consortia continue to generate huge amounts of DNA sequence data. Despite the identification of specific disease-related genes and genetic markers, we still appear to know little about how diverse gene products actually interact with each other or respond to other chemical or biological stimuli. Such information is of course fundamental to understanding complex disease pathways and biochemical processes and, as such, has spawned new fields of investigative genetics, that of functional genomics and proteomics. DNA array technology is emerging as a powerful, high-throughput and versatile tool that can be applied to the study of functional genomics. This article reviews the methodology involved in array analysis and provides insight into how, as an investigative tool, DNA arrays are becoming increasingly useful in understanding fundamental abnormalities in dermatological disease and also in refining the management of patients with certain skin disorders.

Gene Expression Profiling↗

PubMed2001

Hay-Wells syndrome is caused by heterozygous missense mutations in the SAM domain of p63.

Hay-Wells syndrome, also known as ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome (OMIM 106260), is a rare autosomal dominant disorder characterized by congenital ectodermal dysplasia, including alopecia, scalp infections, dystrophic nails, hypodontia, ankyloblepharon and cleft lip and/or cleft palate. This constellation of clinical signs is unique, but some overlap can be recognized with other ectodermal dysplasia syndromes, for example ectrodactyly--ectodermal dysplasia--cleft lip/palate (EEC; OMIM 604292), limb--mammary syndrome (LMS; OMIM 603543), acro-dermato-ungual-lacrimal-tooth syndrome (ADULT; OMIM 103285) and recessive cleft lip/palate--ectodermal dysplasia (CLPED1; OMIM 225060). We have recently demonstrated that heterozygous mutations in the p63 gene are the major cause of EEC syndrome. Linkage studies suggest that the related LMS and ADULT syndromes are also caused by mutations in the p63 gene. Thus, it appears that p63 gene mutations have highly pleiotropic effects. We have analysed p63 in AEC syndrome patients and identified missense mutations in eight families. All mutations give rise to amino acid substitutions in the sterile alpha motif (SAM) domain, and are predicted to affect protein--protein interactions. In contrast, the vast majority of the mutations found in EEC syndrome are amino acid substitutions in the DNA-binding domain. Thus, a clear genotype--phenotype correlation can be recognized for EEC and AEC syndromes.

Abnormalities, Multiple↗

PubMed2001

Three cases of de novo dominant dystrophic epidermolysis bullosa associated with the mutation G2043R in COL7A1.

In the absence of a positive family history, it is often difficult to determine whether a single case of mild-to-moderately severe dystrophic epidermolysis bullosa (DEB) represents autosomal recessive or de novo dominant disease. Recent molecular analyses of the type VII collagen gene, COL7A1, have established that the vast majority of such cases are recessive in nature. Nevertheless, a small number of de novo dominant patients have been documented. In this report, we describe three further examples of de novo dominant disease. In each case the COL7A1 mutation comprised the same glycine substitution, G2043R. This mutation has previously been reported in both dominant DEB pedigrees and as a de novo phenomenon and is the most common COL7A1 mutation in dominant DEB throughout the world. These cases emphasize the importance of molecular analysis in providing accurate genetic counselling in this genodermatosis.

Adolescent↗

PubMed2000

Heterozygous germline missense mutation in the p63 gene underlying EEC syndrome.

Mutations in the p63 gene have recently been delineated as the molecular basis for some cases of the ectrodactyly, ectodermal dysplasia and cleft lip/palate (EEC) syndrome, an autosomal dominant disorder (MIM 129900). In this report, we describe a 35-year-old woman with EEC syndrome and document a heterozygous germline missense mutation, R304W, in exon 8 of the p63 gene. As with most other p63 mutations in EEC syndrome, this mutation has arisen de novo and is located within the core DNA-binding domain of p63. Identification of this mutation has implications for genetic counselling and the feasibility of future DNA-based prenatal diagnosis in this individual.

Abnormalities, Multiple↗

PubMed1998

The association of skin diseases with human herpesvirus 8 infection in HIV carriers.

The seroprevalence to Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus type 8 (HHV-8) was surveyed in human immunodeficiency virus type 1 (HIV-1) carriers with or without skin diseases, and also in HIV-1 negative individuals in Thailand. Using an immunofluorescence assay, the seropositive rates to lytic antigens of HHV-8 in HIV-1 carriers with or without skin diseases were 25% and 7.4%, respectively, but none of HIV-1 negative individuals had antibody. The seroprevalence to HHV-8 antigens was high in HIV positive individuals with low CD4/CD8 ratio, suggesting that HHV-8 is reactivated during the immunosuppressive state. Several polypeptides with apparent molecular weights of 34-38,000 and 40,000, which were specific to HHV-8, were identified by the immunoprecipitation test using the seropositive sera. Our results suggested that HHV-8 co-existed with HIV in HIV-1 carriers and the existence of HHV-8 may be associated with clinical features in the skin.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Clinical effect of dynorphin on heroin addicts.

This study assessed the clinical effectiveness, physiological responses and also adverse effects of dynorphin in heroin dependent detoxication. The subjects were randomly assigned into three groups and received intravenous injections of dynorphin at the dose of 180 (6 patients) or 60 (7 patients) or 0 (8 patients) micrograms/kg three times a day for 6 days. There was no statistical difference in withdrawal syndrome between each group. However, the drug craving feeling in the dynorphin groups was reduced when compared to the placebo group. There was no report of any adverse effects of the drug or abnormal laboratory results from the subjects during the study period.

Adult↗