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Biomedical subjects

I R Walpole

Publications and source records attributed to I R Walpole.

At least 19 recordsLinked to original sources
PubMed1999

Expanding the phenotype of Filippi syndrome: a report of three cases.

This report is of two brothers and a male singleton with clinical characteristics of Filippi syndrome, born to young, healthy, non-consanguineous parents. Their features, which include borderline to milder developmental delay, particularly of speech and language, primary microdontia and previously unreported radiological findings are described to further delineate and expand the clinical spectrum of the condition.

Abnormalities, Multiple↗
PubMed1998

Efficacy of gene testing for von Hippel-Lindau disease.

OBJECTIVE: To determine the efficacy of genetic testing of individuals presenting with features possibly indicative of von Hippel-Lindau (VHL) disease, regardless of other relevant family and clinical details. SETTING AND PARTICIPANTS: Between September 1994 and December 1997, 16 unrelated individuals were referred to Genetic Services of Western Australia by local clinicians and by similar genetic services in other States, for VHL gene mutation analysis because of clinical manifestations suggestive of the diagnosis. METHODS: The subjects were investigated by screening for mutations in the polymerase chain reaction products of the three VHL gene exons using single-stranded conformational polymorphism analysis (SSCP). If no mutations were detected the exons were sequenced, and if no variations were found DNA was examined by Southern analysis for germinal rearrangements. RESULTS: Mutations in the VHL gene were detected in eight of 16 individuals (50%), including 3 individuals with no family history suggestive of VHL disease. Five mutations were detected by SSCP, two by gene sequencing and one by Southern analysis. Each mutation occurred only in a single family and three had not been previously reported. CONCLUSION: Genetic screening of individuals presenting with clinical features suggestive of VHL facilitates confirmation of the diagnosis, accurate genetic counselling and surveillance of at-risk family members. The necessity for costly and time-consuming screening programs can be reduced and screening directed at those carrying the mutation. Our low stringency criteria are justified for screening for VHL mutations.

Genetic Testing↗
PubMed1997

The clinical correlates of a 3' truncating mutation (codons 1982-1983) in the adenomatous polyposis coli gene.

Familial adenomatous polyposis (FAP) is caused by mutations in the adenomatous polyposis coli (APC) gene, and different mutations may produce different clinical pictures. Most mutations occur in the 5' half of the gene, and mutations toward the 3' end are rare. The aim of this study was to document the phenotypes in a family with a truncating mutation at codons 1982-1983, one of the most 3' mutations on record. Colonic polyps in this family were much less numerous, and their growth was delayed compared with the classical FAP picture, and malignant degeneration occurred considerably later. Two individuals had sparse colonic but profuse gastric fundic gland polyposis. Gardner's syndrome stigmata were variable, and a desmoid tumor was recorded in 1 person.

Adenomatous Polyposis Coli↗
PubMed1997

Evaluation of a project to enhance knowledge of hereditary diseases and management.

During 1992 and 1993, in a designated suburban area of Perth, Western Australia, information on hereditary disease was provided for health professionals and the general community. This information was in the form of posters, pamphlets, postal flyers and return letter cards, a static display, newspaper articles, advertisements and radio broadcasts, and professional seminars. The aim of this project was to evaluate the effectiveness of combined strategies to convey practical information about hereditary disease to the community and health professionals. Multiple measures of response evaluation were used, which included structured questionnaire surveys of health professionals and members of the community before and after the project. In the community surveys, respondents who were female, married, middle aged, and parents, and had a higher level of education or were born in Australia, New Zealand, or the United Kingdom were generally better informed about hereditary diseases. This intervention resulted in only meagre changes in community knowledge about hereditary disease, even though promotional materials were shown to be appropriate. General Practitioners (GPs) and Child Health Nurses (CHNs) were supportive of clinical genetic services and recognised a need for continuation of education in this field. There is a rapidly increasing need for community and health professional comprehension of the applications of the new genetic technology. This project indicates that routine educational and health promotion strategies will not be enough to achieve desired levels of knowledge and attitude change.

Adult↗
PubMed1995

Genetic counselling and gene mutation analysis in familial adenomatous polyposis in Western Australia.

OBJECTIVE: To assess the provision of accurate pre-symptomatic genetic testing with DNA analysis and appropriate counselling for individuals and families known to be at high risk of developing familial adenomatous polyposis coli (FAP). PATIENTS AND METHODS: Thirty-one families with clinically and pathologically documented FAP were ascertained from the Western Australian Polyposis Registry. DNA was collected from over 200 individuals in these families to establish their genetic risk status for FAP, either by direct mutation analysis, or by linkage analysis. Individuals undergoing DNA testing were given intensive psychosocial support and counselling. RESULTS: In 19 families DNA-based counselling could not be offered because either the adenomatous polyposis coli (APC) gene mutation could not be detected or there were insufficient family members for linkage analysis. Gene testing yielded mutations of the APC gene in 87 individuals from 12 families; by gene tracking (or linkage analysis) in three families and by mutation analysis in the remaining nine (four of which had only one affected individual). DNA results conformed with a definite clinicopathological diagnosis in 27 FAP patients and, of the remaining 60 high-risk subjects tested, 14 had inherited the mutated APC gene. CONCLUSIONS: DNA analysis allowed accurate genetic counselling for 12 of 31 families affected by FAP, thus improving the medical and personal management in asymptomatic people who would otherwise be subjected to the uncertainty of long term surveillance and repeated colonic examinations. In future a superior biomolecular approach to gene mutation analysis, such as the protein truncation test, will facilitate management for most FAP individuals and families.

Adenomatous Polyposis Coli↗
PubMed1995

Mutation analysis of Western Australian families affected by cystic fibrosis.

OBJECTIVE: To document the results of mutation analysis on 160 individuals with cystic fibrosis and 31 obligate carriers of the cystic fibrosis gene in 191 Western Australian families to facilitate accurate genetic counselling. METHODS: We tested for 17 mutations of the cystic fibrosis gene by either a variation of the polymerase chain reaction amplification refractory mutation system (PCR-ARMS) or with a series of restriction enzyme cuts and dot blots using chemiluminescent probes. RESULTS: At least one of the two intragenic mutations causing cystic fibrosis was identified in 98% of affected individuals and both were detected in 68%. The delta F508 deletion occurred in 89.8% of patients: 51% were homozygous for this defect. In carriers, 85% of the mutations were detected with a panel of 16 probes, identifying 17 intragenic defects: the delta F508 deletion occurred in 72.4%. Both cystic fibrosis mutations were detected in 68% of cystic fibrosis families. CONCLUSIONS: By analysis with 16 intragenic cystic fibrosis genomic probes, we have documented the frequencies of various mutations in the Western Australian population. These data will be useful in accurate genetic counselling for affected families and carrier screening for the general population.

Adult↗
PubMed1994

Improving diagnosis of Huntington's disease by analysis of an intragenic trinucleotide repeat expansion.

OBJECTIVE: To develop an accurate presymptomatic test for Huntington's disease. METHOD: An improved polymerase chain reaction method was used to investigate the pattern of expansions of a CAG repeat sequence located in the 5' region of a gene recently found to produce the protein called Huntingtin. We documented the range of trinucleotide repeat expansions in the responsible gene in 82 affected individuals compared with 80 control subjects from a Western Australian population. RESULTS: The number of expanded repeats ranged from 40 to 73 in affected individuals and from 13 to 38 in normal controls. CONCLUSIONS: Polymerase chain reaction analysis of a CAG repeat sequence in the Huntington's disease gene clearly differentiated between normal and mutated alleles, providing an accurate diagnostic test for the disorder in individuals at risk. This predictive test has met with greater acceptance and demand than methods using family based linkage studies.

Base Sequence↗
PubMed1993

The limitation of referral level fetal ultrasound examination in the detection of spina bifida in Western Australia, 1990-1991.

OBJECTIVE: To ascertain babies born with spina bifida that was not detected by prenatal ultrasound examination performed after 16 weeks' gestational age at Western Australian referral centres, 1990-1991. DESIGN: A retrospective study of the antenatal ultrasound details of those infants born with spina bifida in Western Australia during the 24-month period, 1990 and 1991. Data were collected by interviewing parents, clinically assessing affected individuals and reviewing genetic, clinical and investigative records, and from the Birth Defects Registry of Western Australia. SETTING: Western Australia, which has a relatively high spina bifida birth prevalence of 1 in 1000, has centralised neonatal medical, surgical and genetic services, and a Birth Defects Registry. This enabled us to ascertain all Western Australian neonates with spina bifida for the purposes of this study. There is no universal maternal serum alpha-fetoprotein (MSAFP) screening program and the performance of ultrasonography at referral level is of variable quality. PARTICIPANTS: Newborns with spina bifida and their parents. MAIN OUTCOME MEASURES: Ultrasound screening for spina bifida was deemed to have failed when referral to a specialist imaging centre for the specific purpose of detecting anatomical abnormality after 16 weeks' gestational age gave a falsely negative result. RESULTS: Of the 47 infants born with spina bifida in 1990 and 1991, ultrasound screening at more than 16 weeks' gestational age was documented and was falsely negative in 14. Six of the 14 had a relevant family or medical history for the condition. Five of the lesions were covered and eight of the patients still survive. CONCLUSION: Ad-hoc fetal ultrasound examination via existing referral centres had obvious limitations in detecting spina bifida in a population at low risk. MSAFP screening has a well documented role in detecting neural tube defects, as eight to 10 of the 14 lesions missed by the referral ultrasonography would have been ascertained in a program of this nature. The study indicated that adequate pre-screening clinical histories were not sought, thus limiting the antenatal testing options offered to at-risk couples. This study emphasised the importance of a statewide review of the specificity and sensitivity of the anatomical fetal ultrasound examination, in view of the expansion of this procedure and its variable quality depending on operator experience and equipment quality.

False Negative Reactions↗
PubMed1991

Congenital toxoplasmosis: a large survey in western Australia.

OBJECTIVE: To determine the birth prevalence of congenital toxoplasmosis in Western Australia. DESIGN: A prospective serological study of randomly selected pregnant women and their newborn infants. Paired sera collected from the mothers at their first antenatal visit and cord blood specimens taken from their infants were tested for toxoplasmosis by the direct agglutination test and Toxoplasma IgM-capture enzyme-linked immunosorbent assay. SETTING: A major Perth metropolitan obstetric teaching hospital where approximately one-quarter of infants born in Western Australia during January 1986 to December 1989 inclusive were delivered. PARTICIPANTS: Sera were obtained from 10,207 pregnant women presenting for routine clinical evaluation at their first antenatal visit. Cord blood specimens were taken from 18,908 infants; 7523 of these could be paired to maternal specimens. MAIN OUTCOME MEASURES: Maternal infection was indicated in cases where Toxoplasma specific IgM antibody was present or where an initial maternal specimen gave negative results for Toxoplasma antibody but the paired cord blood specimen gave positive results. Toxoplasma specific IgM antibody in a cord blood specimen indicated fetal infection. RESULTS: Of the 10,207 women 3544 (35%) were Toxoplasma immune at their first antenatal visit; in 11 Toxoplasma specific IgM antibody was detected. There was no serological or clinical evidence of congenital toxoplasmosis in any of the offspring of these 11 mothers. The rate of maternal infection in susceptible pregnancies was 1.6 per 1000; the maternal-fetal transmission rate was estimated to be no greater than 24%. Three of the 18,908 cord blood specimens tested gave positive results for Toxoplasma specific IgM antibody giving a birth prevalence of congenital infection of 0.23 per 1000 births to non-immune mothers. There were no clinical features of congenital infection in these three infants but they will require long-term follow-up. Thirteen of the 14 mothers infected during pregnancy were interviewed retrospectively and in only three was a known risk factor for infection present. CONCLUSIONS: a toxoplasmosis screening programme for pregnant mothers is not justifiable in Western Australia. A public education programme is also likely to have limitations.

Agglutination Tests↗
PubMed1991

Dandy-Walker malformation (variant), cystic dysplastic kidneys, and hepatic fibrosis: a distinct entity or Meckel syndrome?

Dandy-Walker malformation is an unusual finding in Meckel syndrome, which characteristically presents with encephalocele, polydactyly, and cystic renal disease. We report on a family in which three nonviable brothers had Dandy-Walker malformations (variant) with associated enlarged cystic dysplastic kidneys and hepatic fibrosis. The consistent segregation of these abnormalities in all three sibs in the absence of polydactyly and encephalocele suggested the possibility of a distinct syndrome. The clinicopathological findings of the disorder are described and discussed in the context of the phenotypic spectrum of Meckel syndrome.

Adult↗
PubMed1991

Rapp-Hodgkin hypohidrotic ectodermal dysplasia syndrome.

Four members in three generations of a family had Rapp-Hodgkin hypohidrotic ectodermal dysplasia syndrome with variable involvement of teeth, hair, nails and palate, characteristic facies and mild heat tolerance problems. In addition, the proband had a high sweat sodium, hypogenitalism, hypothelia and marked cicatricial scalp atrophy and scarring. Inheritance of the condition was consistent with an autosomal dominant mode and the manifestations are described to delineate further this rare phenotype.

Adult↗
PubMed1990

Clinical considerations in Buschke-Ollendorff syndrome.

This brief report describes a mother and two daughters with the rare Buschke-Ollendorff syndrome. That the typical dermal connective tissue naevi lesions may become less obvious with time and that the condition is not always so "benign" are important clinical features not well recognised. Incorrect diagnosis may lead to embarkation upon hazardous management.

Adult↗
PubMed1990

Autosomal dominant osteopetrosis type II with "malignant" presentation: further support for heterogeneity?

The osteopetroses are a heterogeneous group of disorders characterised by generalised bony sclerosis. The autosomal dominant form usually has a "benign" prognosis, in contrast to the "malignant" course of the autosomal recessive variety. In this paper we describe a kindred in which the phenotypic spectrum varied from an asymptomatic condition in adults to a severely affected infant, presenting with anaemia, hepatosplenomegaly, hydrocephalus and blindness. The findings in this family are reported and discussed to elucidate further the possible genetic heterogeneity in autosomal dominant osteopetrosis.

Adult↗