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Biomedical subjects

J Burn

Publications and source records attributed to J Burn.

At least 91 records · Page 5Linked to original sources
PubMed1996

Natural history of trisomy 18.

It has been suggested that survival in babies with trisomy 18 may be better than previously recognised, and that cardiac surgery may be justified. A population based study spanning seven years in one English health region is presented. The fetal prevalence at 18 weeks was 1 in 4274 and birth prevalence 1 in 8333 live births. Trisomy 18 was detected antenatally in 43% of cases, but almost 90% of those born without a diagnosis were known to be growth retarded in utero. More than 50% of liveborn infants were delivered by caesarean section. The median survival of those born alive was 3 days with no babies living longer than one year. Cardiac malformations were not universal but were present in more than 87% of those for whom there were data. However, in only three cases were cardiac problems implicated in the death of the infants. Cardiac surgery is not likely to improve the survival of infants with trisomy 18 and at present cannot be justified. The most common mode of death was central apnoea.

Adult↗
PubMed1996

Audit of maternal serum screening: strategies to augment counselling in response to women's views.

Women's opinion on the maternal serum screening programme offered at one maternity unit in East Northumberland (1991-1992) was evaluated. The responses from 1,774/2,633 women showed a general acceptance of the test but 722/1,774 (40%) wanted more information and a third, more explanation. Recommendations, which included a 'gold standard' protocol, a video to complement revised patient information literature and a coordinator to facilitate interdisciplinary communication and training with support for midwives, were introduced. The audit cycle was completed by a repeat questionnaire survey of 2,489 women from the postnatal ward (1992-1994) with a 67.3% response. An overall improvement in levels of satisfaction with reduction in, but not eradication of, the need for more information and explanation had occurred. These findings have relevance to the current controversy surrounding the counselling implications of maternal serum screening and have led to the formation of a network of professionals to develop the programme in our region.

Down Syndrome↗
PubMed1996

PPM-X: a new X-linked mental retardation syndrome with psychosis, pyramidal signs, and macroorchidism maps to Xq28.

We report a three-generation family manifesting a previously undescribed X-linked mental retardation syndrome. Four of the six moderately retarded males have had episodes of manic-depressive psychosis. The phenotype also includes pyramidal signs, Parkinsonian features, and macroorchidism, but there are no characteristic dysmorphic facial features. Affected males do not show fragile sites at distal Xq on cytogenetic analysis, nor do they have expansions of the CGG repeats at the FRAXA, FRAXE, or FRAXF loci. Linkage analyses were undertaken, and a maximal LOD score of 3.311 at theta = .0 was observed with the microsatellite marker DXS1123 in Xq28. A recombination was detected in one of the affected males with DXS1691 (Xq28), which gives the proximal boundary of the localization. No distal recombination has been detected at any of the loci tested.

Adolescent↗
PubMed1996

Hereditary desmoid disease due to a frameshift mutation at codon 1924 of the APC gene.

Desmoid tumors are slowly growing fibrous tumors highly resistant to therapy and often fatal. Here, we report hereditary desmoid disease (HDD), a novel autosomal dominant trait with 100% penetrance affecting a three-generation kindred. Desmoid tumors are usually a complication of familial adenomatous polyposis, a predisposition to the early development of premalignant adenomatous polyps in the colorectum due to chain-terminating mutations of the APC gene. In general, one or more members in approximately 10% of the FAP families manifest desmoid tumors. Affected individuals from the HDD kindred are characterized by multifocal fibromatosis of the paraspinal muscles, breast, occiput, arms, lower ribs, abdominal wall, and mesentery. Osteomas, epidermal cysts, and other congenital features were also observed. We show that HDD segregates with an unusual germ-line chain-terminating mutation at the 3' end of the APC gene (codon 1924) with somatic loss of the wild-type allele leading to tumor development.

Adolescent↗
PubMed1995

Clinical and hematologic aspects of the X-linked alpha-thalassemia/mental retardation syndrome (ATR-X).

The hallmarks of the X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome are severe psychomotor retardation, minor facial anomalies, genital abnormalities, and an unusual form of alpha-thalassemia. The demonstration of HbH inclusions in red blood cells after incubation with brilliant cresyl blue confirms the diagnosis. We describe 15 previously unreported cases and analyse the phenotypic and hematologic findings in these subjects and compare them with previously published cases. This study demonstrates the consistency of the main characteristics of this syndrome and extends the phenotype. Developmental changes in phenotype, in particular the coarsening of the facial appearance, are illustrated. The hematologic findings are shown to vary widely; in some cases the manifestation of alpha-thalassemia may be subtle and missed without repeated examination.

Abnormalities, Multiple↗
PubMed1995

Structure of the human MLH1 locus and analysis of a large hereditary nonpolyposis colorectal carcinoma kindred for mlh1 mutations.

Hereditary nonpolyposis colorectal carcinoma is a major cancer susceptibility syndrome known to be caused by inheritance of mutations in at least four genes such as hMSH2, hMLH1, hPMS1, and hPMS2 which encode components of a DNA mismatch repair system. The hMLH1 genomic locus on chromosome 3p has been cloned and shown to cover approximately 58 kilobases of genomic DNA and contain 19 exons. The sequence of all of the intron-exon junctions has been determined and used to develop methods for analyzing each hMLH1 exon for mutations. Using these methods to analyze a 3p-linked hereditary nonpolyposis colorectal carcinoma kindred, we have demonstrated that cancer susceptibility in this family is due to the inheritance of a frame shift mutation in the hMLH1 gene.

Base Sequence↗
PubMed1995

Clinical impact of colonoscopic screening in first-degree relatives of patients with hereditary non-polyposis colorectal cancer.

Sixty-one asymptomatic individuals with an affected first-degree relative from five large hereditary non-polyposis colorectal cancer (HNPCC) kindreds were screened by colonoscopy. Neoplasms were found in nine (15 per cent) of 61 individuals on the first screen. Five subjects had a single adenoma while two had two adenomas each. There were two patients (3 per cent) with malignant neoplasms: one with a Dukes B adenocarcinoma and one with synchronous Dukes C adenocarcinomas in the caecum and ascending colon. These findings support the hypothesis that adenomas do not occur in large numbers in HNPCC families but, because of the high malignant conversion rate, biennial colonoscopy with removal of polyps seen is recommended.

Adenocarcinoma↗
PubMed1995

A gene for autosomal dominant sacral agenesis maps to the holoprosencephaly region at 7q36.

Sacral agenesis is a rare disorder of uncertain incidence that has been reported in diverse populations. Although usually sporadic and most commonly associated with maternal diabetes, there is a hereditary form which may occur in isolation or with a presacral mass (anterior meningocele and/or presacral teratoma) and anorectal abnormalities, which constitute the Currarino triad (MIM 176450). The radiological hallmark of hereditary sacral agenesis is a hemi-sacrum (sickle-shaped sacrum) with intact first sacral vertebra. Bowel obstruction is the usual neonatal presentation, but, unlike other neural tube defects, adult presentation is not uncommon. The major pathology is confined to the pelvic cavity and may present as a space-occupying lesion or meningitis due to ascending infection. All recurrences in families have been compatible with autosomal dominant inheritance except for those associated with the isomerism gene at Xq24-q27.1 (ref. 3). Several associated cytogenetic defects have been reported, including 7q deletions. Previous studies failed to detect linkage to HLA markers, but we now present evidence for a location on 7q36. The same region also contains a gene for holoprosencephaly, an early malformation of the extreme rostral end of the neural tube.

Abnormalities, Multiple↗
PubMed1995

Familial cylindromatosis (turban tumour syndrome) gene localised to chromosome 16q12-q13: evidence for its role as a tumour suppressor gene.

The human skin is a complex organ composed of the surface epidermis, the subjacent dermis (in which blood vessels, lymphatics and nerves are located) and the skin appendages. The latter include hair follicles, sebaceous glands (which secrete lipids that may serve as a permeability barrier, emollient or antimicrobial agent), apocrine glands (which secrete scents) and eccrine glands (which produce sweat for temperature control). Hereditary cylindromatosis (MIM 123850) is a rare autosomal dominant disease characterised by the development of multiple neoplasms originating from the skin appendages. These neoplasms have been termed cylindromas due to their characteristic microscopic architecture and are believed to exhibit apocrine or eccrine differentiation. We have carried out a genome search using two families with this disease, which has provided strong evidence for linkage of cylindromatosis to loci on chromosome 16q12-q13. Using markers close to the cylindromatosis gene, consistent loss of the wild-type allele was observed in 19 tumours from four individuals in the two families, indicating that the gene is likely to be a tumour suppressor gene.

Carcinoma, Adenoid Cystic↗
PubMed1995

Isolation of a gene encoding an integral membrane protein from the vicinity of a balanced translocation breakpoint associated with DiGeorge syndrome.

Deletions within 22q11 have been associated with a wide variety of birth defects embraced by the acronym CATCH22 and including the DiGeorge syndrome, Shprintzen syndrome (velocardiofacial syndrome) and congenital heart disease. It is not known how many genes contribute to this phenotype. Previous studies have shown that a balanced translocation disrupts sequences within the shortest region of deletion overlap for DiGeorge syndrome. A P1 clone was isolated which spans this breakpoint and used to isolate a cDNA encoding a transmembrane protein expressed in a wide variety of tissues. This gene (called IDD) is not disrupted by the translocation, but maps within 10 kb of the breakpoint. Mutation analysis of five affected cases with no previously identified chromosome 22 deletion was negative, but a potential protein polymorphism was discovered. No deletions or rearrangements were detected in these patients following analysis with markers closely flanking the breakpoint, data which emphasize that large (i.e. over 1 Mb) interstitial deletions are the rule in DiGeorge syndrome. The proximity of IDD to the balanced translocation breakpoint and its position within the shortest region of deletion overlap indicate that this gene may have a role, along with other genes, in the CATCH22 haploinsufficiency syndromes.

Amino Acid Sequence↗
PubMed1995

Genetic variation in the COL6A1 region is associated with congenital heart defects in trisomy 21 (Down's syndrome).

Genetic variation in the COL6A1-COL6A2 gene cluster on chromosome 21 was studied in 113 controls and 58 European families (including control and family subgroups of British/Irish origin) having a child with trisomy 21. There were statistically significant differences among subgroups of trisomic children with and without congenital heart defects (CHD) in distributions of definitive, 3-RFLP haplotype classes received from their nondisjoining and disjoining parents. Haplotypes received by trisomic children with CHD from their disjoining parents were not a random sample of controls' haplotypes. Analysis of parental single-RFLP genotypes and linkage disequilibrium patterns confirmed this parent subgroup differed from a random sample of controls. There were no significant differences in parent subgroup genotype distribution at any of nine control loci distributed along chromosome 21q. This sample showed an association between genetic variation in the COL6A1 gene region and congenital heart defects in trisomy 21.

Adolescent↗
PubMed1995

Limb reduction defects in the northern region of England 1985-92.

STUDY OBJECTIVE: To test the hypothesis that children born to mothers living near the sea are at increased risk of limb reduction defects. DESIGN: Descriptive data analysis. SETTING: The northern health region of England. PATIENTS: All children born between 1 January 1985 and 31 December 1992 in the northern region of England with isolated limb reduction defects. MAIN RESULTS: The birth prevalence of isolated limb reduction defects was not affected by the distance the mother lived from the sea. There was some evidence of space-time clustering, but there was no evidence of statistically significant variation in the occurrence of the condition with sex, time of birth (monthly or yearly), or county of birth. CONCLUSIONS: There is no evidence that children born to mothers living near the sea are at increased risk of limb reduction defects.

Cluster Analysis↗
PubMed1995

Kabuki syndrome-like features in monozygotic twin boys with a pseudodicentric chromosome 13.

We present monozygotic twin boys with features of Kabuki syndrome. The twins were discordant for cleft palate and coarctation of the aorta. The occurrence of Kabuki syndrome in monozygotic twins has not been previously reported and reinforces the belief that this condition has a genetic basis. Chromosomal analysis on the boys showed a pseudodicentric chromosome 13 with an inactive centromere and satellite stalks at 13q12.11: 46,XY,psu dic(13)(13pter-->13q12.11::13p12-->13q11.00:: 13q12.11-->13qter). Their phenotypically normal mother appears to carry the same pseudodicentric chromosome 13.

Abnormalities, Multiple↗
PubMed1995

Monozygotic twins with chromosome 22q11 deletion and discordant phenotype.

We report monozygotic twins concordant for 22q11.2 deletion but discordant for clinical phenotype. Both boys show the typical dysmorphic features with short palpebral fissures, square nasal tip, small mouth, and both have nasal speech, but only one twin had a heart defect. They show that the phenotypic variability seen in this microdeletion syndrome cannot be explained on the basis of genotypic differences alone.

Abnormalities, Multiple↗
PubMed1995

Novel mutations and deletions of the KIT (steel factor receptor) gene in human piebaldism.

Piebaldism is an autosomal dominant genetic disorder of pigmentation characterized by white patches of skin and hair. Melanocytes are lacking in these hypopigmented regions, the result of mutations of the KIT gene, which encodes the cell surface receptor for steel factor (SLF). We describe the analysis of 26 unrelated patients with piebaldism-like hypopigmentation--17 typical patients, 5 with atypical clinical features or family histories, and 4 with other disorders that involve white spotting. We identified novel pathologic mutations or deletions of the KIT gene in 10 (59%) of the typical patients, and in 2 (40%) of the atypical patients. Overall, we have identified pathologic KIT gene mutations in 21 (75%) of 28 unrelated patients with typical piebaldism we have studied. Of the patients without apparent KIT mutations, none have apparent abnormalities of the gene encoding SLF itself (MGF), and genetic linkage analyses in two of these families are suggestive of linkage of the piebald phenotype to KIT. Thus, most patients with typical piebaldism appear to have abnormalities of the KIT gene.

Adolescent↗