PubMed Health⌕ Search

Biomedical subjects

J A Raeburn

Publications and source records attributed to J A Raeburn.

At least 19 recordsLinked to original sources
PubMed2000

The clinical genetics of hidradenitis suppurativa revisited.

A familial form of hidradenitis suppurativa (HS) with autosomal dominant inheritance was described in a study conducted 15 years ago in Nottingham but has not been systematically confirmed elsewhere. Prior to commencing molecular genetic studies, we wanted to test the validity of the previous study by assessing its reproducibility on the basis of a strict, newly devised disease definition for HS. We were also interested whether new cases of the disease had arisen meantime in the study group as should be expected for an autosomal dominant disease. We reviewed 14 surviving probands and their families. Seven of these probands had previously been noted to have a positive family history whereas the others had been classified as having a negative or possible family history. One hundred and thirty-two family members were assessed for their respective disease status. Participants were initially contacted by telephone or letter, and those who acknowledged a history of at least one previous boil were invited for a personal examination and interview. Only personally examined individuals were classified as a case. Twenty-eight relatives with HS were detected in total, and 27 of these were in the group previously labelled family history positive. Nine of these cases had not been detected in the previous study and in at least seven of these the disease had developed after the previous study had been conducted. Only twice did our criteria fail to confirm cases that had been labelled as HS in the previous study. Both times we classified the patients as 'possibly affected'. A further 16 relatives were judged to be possibly affected. In the group with positive family history we found 10 affected and nine possibly affected individuals among 37 surviving first-degree relatives of HS sufferers. Our findings support the concept of a familial form of HS with autosomal dominant inheritance. An insufficiently sensitive disease definition, a variable degree of gene penetrance and possibly a hormonal influence on gene expression may explain the reduced risk to first-degree relatives, which falls short of the expected 50% mark. Molecular genetic studies to clarify whether one or more gene(s) are involved in HS are now necessary and have been commenced.

Adult↗
PubMed1997

Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family.

Holt-Oram syndrome is a developmental disorder affecting the heart and upper limb, the gene for which was mapped to chromosome 12 two years ago. We have now identified a gene for this disorder (HOS1). The gene (TBX5) is a member of the Brachyury (T) family corresponding to the mouse Tbx5 gene. We have identified six mutations, three in HOS families and three in sporadic HOS cases. Each of the mutations introduces a premature stop codon in the TBX5 gene product. Tissue in situ hybridization studies on human embryos from days 26 to 52 of gestation reveal expression of TBX5 in heart and limb, consistent with a role in human embryonic development.

Abnormalities, Multiple↗
PubMed1996

Holt-Oram syndrome: a clinical genetic study.

A clinical and genetic study of the Holt-Oram syndrome (HOS) has been carried out in the United Kingdom involving 55 cases designated Holt-Oram syndrome, together with their parents and sibs. Data from the clinical assessment of both familial and isolated cases were used to define the HOS phenotype and to outline the spectrum of abnormalities, especially factors affecting severity. Skeletal defects affected the upper limbs exclusively and were bilateral and asymmetrical. They ranged from minor signs such as clinodactyly, limited supination, and sloping shoulders to severe reduction deformities of the upper arm (4.5%). The radial ray was predominantly affected than the right. All affected cases showed evidence of upper limb involvement. Cardiac defects were seen in 95% of familial cases and included both atrial septal defect (ASD, 34%) and ventricular septal defect (VSD, 25%); 39% had only ECG changes. Cardiac involvement ranged from asymptomatic conduction disturbances to multiple structural defects requiring surgery in infancy. Sudden death could be caused by heart block. Inheritance was autosomal dominant with 100% penetrance and no evidence of reduced fitness. Increasing severity occurred in succeeding generations consistent with anticipation.

Abnormalities, Multiple↗
PubMed1996

Familial autosomal dominant dopa responsive Parkinson's disease in three living generations showing extreme anticipation and childhood onset.

We describe a three generation family with Parkinson's disease showing autosomal dominant inheritance with extreme anticipation. Familial Parkinson's disease in three living generations is extremely rare, and anticipation is an unusual and interesting feature. Anticipation was shown in all generations and may have involved previous generations. Some cases of familial Parkinson's disease may therefore involve a trinucleotide repeat gene as part of the causal mechanism.

Age of Onset↗
PubMed1994

Holt-Oram syndrome is a genetically heterogeneous disease with one locus mapping to human chromosome 12q.

Holt-Oram syndrome (HOS) is an autosomal dominant condition affecting the heart and upper limbs. We have sought to identify the location of this gene using microsatellite DNA markers in a linkage study. Of seven families analysed, five show linkage between HOS and markers on chromosome 12q. But the two remaining families, phenotypically indistinguishable from the others, do not show this linkage. Analysis with the computer program HOMOG indicates that HOS is a heterogeneous disease. Our analysis places one HOS locus in a 21 cM interval in the distal region of chromosome 12q. The localization of a gene for HOS, reported here, represents an important step towards a better understanding of limb and cardiac development.

Abnormalities, Multiple↗
PubMed1994

Genetic analysis of a kindred with X-linked mental handicap and retinitis pigmentosa.

A kindred is described in which X-linked nonspecific mental handicap segregates together with retinitis pigmentosa. Carrier females are mentally normal but may show signs of the X-linked retinitis pigmentosa carrier state and become symptomatic in their later years. Analysis of polymorphic DNA markers at nine loci on the short arm of the X chromosome shows that no crossing-over occurs between the disease and Xp11 markers DXS255, TIMP, DXS426, MAOA, and DXS228. The 90% confidence limits show that the locus is in the Xp21-q21 region. Haplotype analysis is consistent with the causal gene being located proximal to the Xp21 loci DXS538 and 5'-dystrophin on the short arm of the X chromosome. The posterior probability of linkage to the RP2 region of the X chromosome short arm (Xp11.4-p11.23) is .727, suggesting the possibility of a contiguous-gene-deletion syndrome. No cytogenetic abnormality has been identified.

Adolescent↗
PubMed1992

Tightly linked polymorphic markers for fragile X syndrome and prenatal cytogenetic diagnostic experience.

Linkage analysis using the polymorphic loci DXS369, DXS296, DXS297 and DXS306 was carried out on a cohort of 17 families segregating for fragile X syndrome. The observed recombination fractions at: DXS369 (Zmax = 3.02; theta = 0.06), DXS297 (Zmax = 2.92; theta = 0.0), DXS296 (Zmax = 3.82; theta = 0.0), DXA306 (Zmax = 4.55; theta = 0.05) confirm that these loci are tightly linked to FRAXA. Our experience in the cytogenetic analysis of 58 at risk pregnancies by chorionic villus or fetal blood sample examination documents a false negative rate in obligate carrier male pregnancies for CVS of 11% and for FBS of 3%.

Cytogenetics↗
PubMed1992

Delivery of genetic screening services.

This paper describes the genetic services in the United Kingdom and how the evolution of genetic screening services is taking place. Since these Community Genetic Services depend on the offer of a screening test that affects the whole population, it is essential that the community is given genetic education and an opportunity to discuss the issues before services are initiated. In this way, the differing beliefs and needs of individual communities are appropriately taken into account. The development of screening services for cystic fibrosis will show whether this community-orientated model can be successful.

Community Health Services↗
PubMed1991

What do young people think about screening for cystic fibrosis?

We investigated the knowledge of cystic fibrosis and the views about neonatal and carrier screening in 216 school students aged 14 to 16 years. This work was completed before the published identification of the cystic fibrosis gene in September 1989. Although initial knowledge of cystic fibrosis was low (only 17% of the students knew that the disease affected the lungs), there was good recall of basic information about cystic fibrosis and of recessive inheritance after a brief lecture. A total of 86% considered that carrier detection should be offered routinely and 88% felt that an offer of prenatal diagnosis for cystic fibrosis should be made if both prospective parents were known to be carriers. We believe that pilot studies of cystic fibrosis carrier screening in schools should be undertaken.

Adolescent↗
PubMed1989

Predictive testing for Huntington's disease with linked DNA markers.

Availability of new DNA markers, more tightly linked to the Huntington's disease (HD) locus than the original G8 (D4S10) probes, has improved predictive accuracy for both presymptomatic and prenatal exclusion testing. 50 predictive tests were carried out on high-risk individuals. 6 of these were on first-trimester chorionic villus biopsy specimens; in 2 cases the HD gene was not transmitted to the fetus while in 4 cases no exclusion could be made. The remaining 44 tests were on adults with either 25 or 50% risk of manifesting the disease; 19 had a greatly increased risk and 25 a substantially decreased risk of HD. Family structures in Scotland are suitable for testing about 75% of potentially affected individuals, and the new generation of DNA markers makes virtually all families fully informative.

Adult↗
PubMed1989

Presymptomatic testing for Huntington's disease. A case complicated by recombination within the D4S10 locus.

Presymptomatic testing for Huntington's disease (HD) is possible through the use of restriction fragment length polymorphisms (RFLPs) at the closely linked D4S10 locus. Recombination between the HD and D4S10 loci will occur in 4%-5% of meioses, and is a well-recognised complication of predictive testing. Recombination between RFLPs within the D4S10 locus is a rare event and can usually be ignored. We report a case where such an intra-locus recombination frustrated attempts to predict the chance of a high-risk individual inheriting the HD gene.

Adult↗