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Biomedical subjects

J Goldblatt

Publications and source records attributed to J Goldblatt.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1995

Peroxisomal assembly defects: clinical, pathologic, and biochemical findings in two patients in a newly identified complementation group.

We describe the clinical, pathologic, and biochemical findings for two peroxisome-deficient patients in a newly identified complementation group. Both patients had biochemical findings typical of patients with peroxisome biogenesis disorders. However, whereas one patient had the typical clinicopathologic features of Zellweger syndrome, the other patient's phenotype was atypical.

Catalase↗
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↗
PubMed1994

Familial hemifacial microsomia due to autosomal dominant inheritance. Case reports.

Hemifacial microsomia is a rare dentofacial anomaly which is regarded as a separate entity to Goldenhar syndrome and primarily affects the structures of the first branchial arch. It has a heterogeneous aetiology and tends to occur sporadically, though positive family histories have been reported. This paper reports on individuals in two generations of a family that has overlapping features of hemifacial microsomia and Goldenhar syndrome segregating as an autosomal dominant condition.

Adolescent↗
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↗
PubMed1993

Verification of carrier status for Becker muscular dystrophy from analysis of a blighted ovum.

The polymerase chain reaction (PCR) was used on material from a blighted ovum to confirm indirectly the carrier status of a woman with a family history of Becker muscular dystrophy. Conventional testing including creatine kinase levels, muscle biopsy, and EMG had been inconclusive, and on the basis of one elevated creatine kinase level, the woman had been designated a possible carrier. Ultrasound examination at 10 weeks of pregnancy indicated a blighted ovum, from which DNA was subsequently extracted and subjected to PCR testing for determination of sex and genotypic status with respect to the known familial deletion of the dystrophin gene. The blighted ovum was found to have a Y chromosome and also to be deleted for at least exon 6 of the dystrophin gene, indirectly indicating that the mother most likely carried the family mutation for Becker muscular dystrophy.

Adult↗
PubMed1993

Hereditary gingival fibromatosis with a recessive mode of inheritance. Case reports.

Hereditary gingival fibromatosis is characterized by varying degrees of attached gingival hyperplasia and may in rare cases present as a feature of a generalized syndrome. It is usually inherited as an autosomal dominant condition though recessive forms are described. The dental and genetic features of an affected brother and sister with a probably unique autosomal recessive hereditary fibromatosis syndrome are presented.

Adolescent↗
PubMed1992

Ellis-van Creveld syndrome in a Western Australian aboriginal community. Postaxial polydactyly as a heterozygous manifestation?

OBJECTIVE: To report two children with Ellis-van Creveld syndrome in an extended kindred of Western Australian Aboriginal descent. Furthermore, to document two family members with isolated postaxial polydactyly of the feet as probable heterozygous manifestations of the Ellis-van Creveld gene. CLINICAL FEATURES: Male and female second cousins with short limbs, postaxial polydactyly and cardiac malformations are described. CONCLUSIONS: It is proposed that founder effect and random genetic drift resulted in a relatively high frequency of the Ellis-van Creveld gene in the Aboriginal people of Western Australia. In addition, further evidence is provided for the postulate that isolated postaxial polydactyly is a heterozygous manifestation of the gene.

Ellis-Van Creveld Syndrome↗
PubMed1992

Two distinct mutations in a single dystrophin gene: chance occurrence or premutation?

We report on a kindred segregating 2 distinct mutations of a dystrophin gene. DNA analysis showed that the second mutation, a deletion, arose in the same gene carrying the primary defect which produced a Becker phenotype in the affected males. The DNA data for this family are reported and the alternative explanations of chance occurrence and premutation are discussed to explain these unusual findings.

Child↗
PubMed1992

Autosomal recessive gingival fibromatosis with distinctive facies.

Hereditary gingival fibromatosis is a rare condition occurring as an isolated anomaly or as part of a genetic syndrome. The isolated or syndromic disorders are usually inherited in an autosomal dominant manner, but an autosomal recessive form has been suggested. We report on male and female siblings who have gingival fibromatosis in association with specific facial dysmorphism. Their phenotype is depicted and described to document this hitherto unreported autosomal recessive gingival fibromatosis syndrome.

Adolescent↗
PubMed1992

A new form of X-linked, high-frequency, sensorineural deafness.

A kindred is described in which five male members over three generations manifested a high-frequency deafness. Their isolated sensorineural hearing loss was non-progressive and only in the 1500-8000 Hz range. The pattern of inheritance and nature of the auditory deficit would suggest it is a previously undescribed X-linked form of deafness.

Aged↗
PubMed1991

Clinical phenotype of Gaucher disease in relation to properties of mutant glucocerebrosidase in cultured fibroblasts.

We have investigated several parameters of glucocerebrosidase in cultured skin fibroblasts from patients with various clinical phenotypes of Gaucher disease. In this study no strict correlation was found between the clinical manifestations of Gaucher disease and the parameters investigated in fibroblasts. These parameters included the specific activity of the enzyme in extracts towards natural lipid and artificial substrate in the presence of different activators; the enzymic activity per unit of glucocerebrosidase protein; the rate of synthesis of the enzyme and its stability; and the post-translational processing of the enzyme. In addition, the activity in situ of glucocerebrosidase in fibroblasts was investigated using a novel method by analysis of the catabolism of NBD-glucosylceramide in cells that were loaded with bovine serum albumin-lipid complexes. Again, no complete correlation with the clinical phenotype of patients was detectable. Glucocerebrosidase in fibroblasts from most non-neuronopathic (type 1) Gaucher disease patients differs in some aspects from enzyme in cells from patients with neurological forms (types 2 and 3). The stimulation by activator protein and phospholipid is clearly more pronounced in type 1 than in types 2 and 3; the enzymic activity per unit of glucocerebrosidase protein in type 1 is severely reduced in the presence of taurocholate and the amount of glucocerebrosidase appears (near) normal in contrast to the situation in types 2 and 3 Gaucher fibroblasts. However, this distinction was not always consistent; glucocerebrosidase in fibroblasts from some type 1 Gaucher patients, particularly some South African cases, was comparable in properties to enzyme in type 2 and 3 patients.

Cathepsin D↗
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↗