Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Data Linkage”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 649 records · Page 36Linked to original sources
PubMed1992

Yeast artificial chromosomes spanning 8 megabases and 10-15 centimorgans of human cytogenetic band Xq26.

A successful test is reported to generate long-range contiguous coverage of DNA from a human cytogenetic band in overlapping yeast artificial chromosomes (YACs). Seed YACs in band Xq26 were recovered from a targeted library of clones from Xq24-q28 with 14 probes, including probes for the hypoxanthine guanine phosphoribosyltransferase- and coagulation factor IX-encoding genes and nine probes used in linkage mapping. Neighboring YACs were then identified by 25 "walking" steps with end-clones, and the content of 71 probes in cognate YACs was verified by further hybridization analyses. The resultant contig extends across 8 million base pairs, including most of band Xq26, with an order of markers consistent with linkage data. YAC-based mapping, thus, permits steps toward a fully integrated physical and genetic map and is probably adequate to sustain most of the human genome project.

Blotting, Southern↗
PubMed2006

A long-term population-based clinical and morbidity profile of Angelman syndrome in Western Australia: 1953-2003.

PURPOSE: To investigate the incidence, clinical presentation and associated comorbidities of Angelman syndrome (AS) in Western Australia, with establishment of an information database for the disorder. METHODS: Data were collected from Disability Services Commission files, supplemented by datasets provided by the Western Australian Data Linkage Unit. The analysis was retrospective and quantitative. RESULTS: Thirty-four individuals (two deceased) were identified (19 F, 15 M), with a mean age of 21.6 years; 52.9% had an IQ < 40, with the remainder of IQ 40-69. The incidence was one in 40,000 births and mean age at diagnosis was 5.8 years. The mean age of the 23 home residents was 20.2 years compared to 27.9 years in the nine individuals in sheltered accommodation. In general, the patients exhibited a typical AS clinical presentation. A median of 5.5 (range 0-20) hospital admissions was recorded per person, with epilepsy, gastrointestinal disorders, and dental work all common reasons for admission. CONCLUSIONS: The estimated incidence was low compared to other reports, as was the proportion of IQ < 40. AS cases required substantial levels of medical care, especially those who were epileptic. An increase in the future numbers of AS patients needing sheltered accommodation is predicted.

Adolescent↗
PubMed2003

Blood morphine levels in naltrexone-exposed compared to non-naltrexone-exposed fatal heroin overdoses.

The aim of this study was to investigate the association between prior exposure to naltrexone and increased risk of fatal heroin overdose using a review of toxicology reports for heroin-related fatalities between July 1997 to August 1999 for two groups: those treated with oral naltrexone and those who were not treated. Additional information for the oral naltrexone group was obtained from clinic files. Naltrexone-treated deaths were identified from the patient database at the Australian Medical Procedures Research Foundation (AMPRF), Perth, Western Australia (WA) through the Western Australian Department of Health, Data Linkage Project. Non-treated cases were identified from the database at the Forensic Science Laboratory, State Chemistry Centre (WA). We identified and investigated blood morphine concentrations following 21 fatal heroin overdoses with prior exposure to naltrexone and in 71 non-naltrexone-exposed cases over the same time period. The proportion of deaths where heroin use was a major contributing factor was little different in the non-naltrexone compared to the naltrexone-exposed group. Furthermore, in 'acute opiate toxicity' deaths, blood morphine levels were lower in non-naltrexone-exposed compared with naltrexone-exposed cases. Although there was a higher number of deaths designated as rapid (i.e. occurring within 20 minutes) in the naltrexone-exposed (89%) compared with the non-exposed group (72%) this was not statistically significant. Other drug use in relation to heroin-related fatalities is discussed. Findings do not support the hypothesis that prior exposure to naltrexone increases sensitivity to heroin toxicity.

Adult↗
PubMed1999

Epidemiology of tobacco use among US adolescents.

Among persons in the United States under age 18 years, every day more than 6000 try cigarette smoking for the first time and more than 3000 become daily smokers. The overwhelming majority of adults who smoke began by age 18 years. Slightly more than one-third of US high school students were cigarette smokers in 1997. In recent years, males were about as likely as females to smoke. American Indians/Alaska Natives and whites were more likely to smoke than were Hispanics, African-Americans, and Asian-Americans/Pacific Islanders. Overall, cigarette smoking prevalence declined in the late 1970s or early 1980s, leveled off in the 1980s, and increased in the 1990s. The decline in prevalence among African-Americans was especially noteworthy. Among US high school students in 1997, the prevalence of cigar smoking was higher than that of smokeless tobacco use. Indicators of nicotine dependence are prevalent among adolescents who use tobacco products. Efforts to: (1) improve the validity of self-reported behaviors; (2) increase access to school dropouts and infrequent school attendees; and (3) improve school participation rates, data availability, and data linkage systems will benefit the field. Qualitative research can suggest variables to be added to survey questionnaires. Methods research should be conducted to better quantify and explain differences between survey estimates. Tracking relevant environmental variables and new tobacco products will expand the science base and facilitate appropriate public health action.

Adolescent↗
PubMed2004

Factors associated with higher levels of injury severity in occupants of motor vehicles that were severely damaged in traffic crashes in Kentucky, 2000-2001.

OBJECTIVES: The majority of motor vehicle occupants who were killed or hospitalized in crashes in Kentucky in 2000-2001 occupied vehicles that were severely damaged in the crash. Even so, overall only a small percentage of all severely damaged vehicle occupants were killed or hospitalized. The purpose was to identify occupant, vehicle, crash, and roadway/environmental factors that were associated with increased risk of severe injury in crashes where the occupant's vehicle was severely damaged. METHODS: This study probabilistically linked Kentucky's statewide motor vehicle crash and inpatient hospital discharge data files for 2000 and 2001, and selected cases representing occupants of vehicles that were reported by police as having either "severe" or "very severe" damage. For occupants who were identified through data linkage as having been hospitalized, the Injury Severity Score (ISS) was calculated using ICDMAP-90 software, and the scores were stratified into the following categories: critical (>24), severe (15-24), moderate (9-14), and mild (<9). We then created an outcome variable, injury severity level, with five levels: killed; hospitalized with at least moderate injuries (ISS = critical, severe, or moderate); hospitalized with mild injuries (ISS = mild); injured according to the police report but not hospitalized; and no apparent injury according to the police report. We performed a stepwise, ordinal logistic regression of injury severity, using independent variables identified from the existing crash literature. RESULTS: Occupant risk factors for higher levels of injury severity selected by the regression were age (risk increased with age, other factors being equal), female gender, restraint non-use, ejection from the vehicle, and driver impairment (by alcohol and/or drugs). Crash risk factors included head-on collision, collision with a fixed object, vehicle rollover, and vehicle fire. Roadway/environmental factors were federal- or state-maintained roadway and posted speed limit 89 kph (55 mph) or greater. CONCLUSIONS: Many of the identified risk factors are explicitly or implicitly mentioned in the strategic plans of key organizations involved in highway safety and injury prevention in Kentucky. Our analysis provides additional evidence of their importance, and confirms that their mitigation will reduce injury severity in crashes involving severe vehicle damage. Additionally, older occupants and female occupants showed increased risks of serious injury, but to our knowledge these factors are not currently addressed in any state plans. An opportunity exists to clarify the nature of these risks through further studies, which might lead to the identification of countermeasures specific to these populations.

Accidents, Traffic↗
PubMed2000

Allelic association of gene markers on chromosome 11q in Italian families with atopy.

UNLABELLED: In our study, the genetic linkage of the Fcepsilon RIbeta gene with atopy in 77 affected sibling pairs recruited from an Italian panel of 201 subjects has been examined. Atopy was defined by the presence of a positive skin prick test to one or more common aeroallergens, a positive RAST test to one or more common aeroallergens and an elevated circulating total IgE. Genotype analysis was performed by PCR amplification of Fcepsilon RIbeta CA and CI11-319 CA microsatellites. All the family members were also tested for the Ilepsilon 181 mutation with the ARMS method and for Leu181/Leu183 polymorphism. Seventy-two point five percent (72.5%) of the affected sibling pairs shared their maternal allele and 27.5% did not. Therefore, an increased maternal allele sharing was observed: chi2 = 8.10, p < 0.01. Comparing paternal versus maternal allele sharing, a significant difference was observed for the C1II-319 CA marker (chi2 = 4.32, p < 0.05). Atopy phenotype with positive skin prick test, RASTs, and high total serum IgE also showed greater sharing of maternal than paternal alleles in affected sibling pairs. Of the 201 subjects studied, 17 (8.4%) were positive for Leu181. Ten of these were children and seven (70%) had inherited the variant maternally. The seven children had maternally inherited Leu181/Leu183 and were atopic. Within this sample the maternal inheritance of Fcepsilon RIbeta Leu181/Leu183 was associated with an increased risk of IgE responses to common allergens, raised eosinophil counts and increased skin prick test reactions. Therefore, the variant identified a genetic risk factor for atopy. CONCLUSION: The central role of Fcepsilon RIbeta in atopy and the linkage data presented here point to the possibility that genetic variation in Fcepsilon RIbeta or its controlling element may cause differences in the extent of IgE responses between atopic and non-atopic subjects. A search for such mutations or polymorphisms will need to take into account some carriers of atopy among the normal population and genetic heterogeneity among atopic individuals.

Adolescent↗
PubMed2004

Risk factors for suicide and other deaths following hospital treated self-poisoning in Australia.

OBJECTIVE: To analyze the risk factors for suicide, premature death and all-cause death in a representative population of hospital-treated deliberate self-poisoning patients. METHOD: A prospective cohort study using data-linkage between the Hunter Area Toxicology Service Database and the National Death Index of the Australian Institute of Health and Welfare, from January 1991 to December 2000. RESULTS: There were 4105 subjects, of whom 228 (5.6%) died, 122 (2.9%) by premature death and 58 (1.4%) by suicide. The probability of suicide after 10 years follow-up was 2%. The adjusted hazard ratios (95% CI) for suicide were: 'disorders usually diagnosed in infancy, childhood and adolescence', 5.28 (95% CI = 2.04-13.65): male gender, 4.25 (95% CI = 2.21-8.14); discharge to involuntary psychiatric hospital admission, 3.20 (95% CI = 1.78-5.76); and increasing age, 1.02 (95% CI = 1.01-1.04). Men and women showed different patterns of multivariate risks, although increased risk with increasing age and discharge to an involuntary psychiatric admission was true for both. The standardized all-cause mortality ratio (95% CI) was: for men, 6.42 (95% CI = 5.44-7.57), and for women 4.39 (95% CI = 3.56-5.41). The standardized suicide mortality ratio (95% CI) was: for men, 20.55 (95% CI = 15.24-27.73), and for women 22.95 (95% CI = 13.82-38.11). CONCLUSIONS: Men and women have different risk factors for subsequent suicide after self-poisoning. Hospital-treated self-poisoning patients have increased risk of subsequent suicide, premature and all-cause death. Psychiatric assessment, leading to discharge decisions, is worthwhile in identifying patients at long-term risk of suicide, premature and all-cause death.

Adolescent↗
PubMedDate not supplied

Non-suicidal deaths following hospital-treated self-poisoning.

OBJECTIVE: To quantify the non-suicidal mortality subsequent to hospital treated self-poisoning, and to identify risk factors for non-suicidal death. METHOD: A prospective longitudinal cohort design was used, with data-linkage between the Hunter Area Toxicology Service database and the National Death Index. All patients with deliberate self-poisoning for a 10-year period (1991-2000) were studied and the first episode in the period was used as the index episode. The outcomes were: accidental, 'natural' and non-suicidal death, with follow-up for the study duration. RESULTS: There were 4044 patients studied, and 170 (4.2%) of these had non-suicidal death; 64 were accidental and 106 were 'natural' cause deaths. The standardized mortality ratio (95% CI) for non-suicidal death for males, females and combined were 4.98 (4.08-6.07), 3.78 (3.0-4.75) and 4.20 (3.62-4.88), respectively. The increased mortality was apparent for both males and females, and was more marked in the younger age groups. For non-suicidal death the adjusted hazard ratio (95% CI) for increased risk were: increasing age 1.07 (1.06-1.08), male gender 1.77 (1.24-2.52), psychiatric diagnosis of substance related disorder 1.49 (1.03-2.16), prescription of a respiratory drug 2.69 (1.31-5.55), and prescription of an anti-diabetic drug 1.95 (0.93-4.07), while psychiatric diagnosis of adjustment disorder 0.64 (0.38-1.053) was associated with decreased risk. CONCLUSIONS: Patients who present with self-poisoning have increased mortality from accidental and 'natural' causes. Long-term treatment goals for these patients need to address non-suicide mortality in addition to suicide mortality.

Accidents↗
PubMed1999

Hyperparathyroidism-jaw tumor syndrome: the HRPT2 locus is within a 0.7-cM region on chromosome 1q.

Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is an autosomal dominant disease characterized by the development of multiple parathyroid adenomas and multiple fibro-osseous tumors of the maxilla and mandible. Some families have had affected members with involvement of the kidneys, variously reported as Wilms tumors, nephroblastomas, and hamartomas. The HPT-JT gene (HRPT2) maps to chromosome 1q25-q31. We describe further investigation of two HPT-JT families (K3304 and K3349) identified through the literature. These two expanded families and two previously reported families were investigated jointly for linkage with 21 new, closely linked markers. Multipoint linkage analysis resulted in a maximum LOD score of 7.83 (at recombination fraction 0) for markers D1S2848-D1S191. Recombination events in these families reduced the HRPT2 region to approximately 14.7 cM. In addition, two of these four study families (i.e., K3304 and K11687) share a 2.2-cM length of their (expanded) affected haplotype, indicating a possible common origin. Combining the linkage data and shared-haplotype data, we propose a 0.7-cM candidate region for HRPT2.

Adenoma↗
PubMed2001

Incidence of transitional cell carcinoma and arsenic in drinking water: a follow-up study of 8,102 residents in an arseniasis-endemic area in northeastern Taiwan.

A significant association between ingested arsenic and bladder cancer has been reported in an arseniasis-endemic area in southwestern Taiwan, where many households share only a few wells in their villages. In another arseniasis-endemic area in northeastern Taiwan, each household has its own well for obtaining drinking water. In 1991-1994, the authors examined risk of transitional cell carcinoma (TCC) in relation to ingested arsenic in a cohort of 8,102 residents in northeastern Taiwan. Estimation of each study subject's individual exposure to inorganic arsenic was based on the arsenic concentration in his or her own well water, which was determined by hydride generation combined with atomic absorption spectrometry. Information on duration of consumption of the well water was obtained through standardized questionnaire interviews. The occurrence of urinary tract cancers was ascertained by follow-up interview and by data linkage with community hospital records, the national death certification profile, and the cancer registry profile. Cox proportional hazards regression analysis was used to estimate multivariate-adjusted relative risks and 95% confidence intervals. There was a significantly increased incidence of urinary cancers for the study cohort compared with the general population in Taiwan (standardized incidence ratio = 2.05; 95% confidence interval (CI): 1.22, 3.24). A significant dose-response relation between risk of cancers of the urinary organs, especially TCC, and indices of arsenic exposure was observed after adjustment for age, sex, and cigarette smoking. The multivariate-adjusted relative risks of developing TCC were 1.9, 8.2, and 15.3 for arsenic concentrations of 10.1-50.0, 50.1-100, and >100 microg/liter, respectively, compared with the referent level of < or =10.0 microg/liter.

Adult↗
PubMed2001

Statistical modeling of interlocus interactions in a complex disease: rejection of the multiplicative model of epistasis in type 1 diabetes.

In general, common diseases do not follow a Mendelian inheritance pattern. To identify disease mechanisms and etiology, their genetic dissection may be assisted by evaluation of linkage in mouse models of human disease. Statistical modeling of multiple-locus linkage data from the nonobese diabetic (NOD) mouse model of type 1 diabetes has previously provided evidence for epistasis between alleles of several Idd (insulin-dependent diabetes) loci. The construction of NOD congenic strains containing selected segments of the diabetes-resistant strain genome allows analysis of the joint effects of alleles of different loci in isolation, without the complication of other segregating Idd loci. In this article, we analyze data from congenic strains carrying two chromosome intervals (a double congenic strain) for two pairs of loci: Idd3 and Idd10 and Idd3 and Idd5. The joint action of both pairs is consistent with models of additivity on either the log odds of the penetrance, or the liability scale, rather than with the previously proposed multiplicative model of epistasis. For Idd3 and Idd5 we would also not reject a model of additivity on the penetrance scale, which might indicate a disease model mediated by more than one pathway leading to beta-cell destruction and development of diabetes. However, there has been confusion between different definitions of interaction or epistasis as used in the biological, statistical, epidemiological, and quantitative and human genetics fields. The degree to which statistical analyses can elucidate underlying biologic mechanisms may be limited and may require prior knowledge of the underlying etiology.

Animals↗
PubMed1981

Genetics of aldehyde dehydrogenase isozymes in the mouse: evidence for multiple loci and localization of Ahd-2 on chromosome 19.

Electrophoretic and activity variation of the cytoplasmic isozyme of aldehyde dehydrogenase (designated AHD-B4) was observed among inbred strains and Harwell linkage-testing stocks of Mus musculus. The phenotypes are inherited in a normal Mendelian fashion, with two alleles showing co-dominant expression at a single locus (Ahd-2). The locus was shown to segregate independently of Ahd-1 (encoding the mitochondrial AHD-A2 isozymes on chromosome 4; HOLMES 1978). Linkage data of Ahd-2 with ep (pale ears), ru (ruby eyes) and bm (brachymorphic) suggest that it is localized near the centromeric end of chromosome 19. Electrophoretic evidence for a third AHD isozyme (designated AHD-Cy), which is predominantly localized in the liver microsomal fraction, is also presented.

Aldehyde Dehydrogenase↗
PubMed1999

The structural heterogeneity of the lipooligosaccharide (LOS) expressed by pathogenic non-typeable Haemophilus influenzae strain NTHi 9274.

Nontypeable Haemophilus influenzae (NTHi) is an important pathogen responsible for otitis media in children and of pneumonitis in adults with depressed resistance. NTHi is acapsular and, therefore, capsular polysaccharide-based vaccines are ineffective for preventing infections by this pathogen. Recently it was found that a detoxified lipooligo-saccharide (LOS) conjugate from NTHi 9274 induced bactericidal antibodies effective against a large number of NTHi isolates, and conferred protection against NTHi otitis media in chinchillas (X.-X.Gu et al., 1996, Infect. Immun.,64, 4047-4053; X. -X.Gu et al., 1997., Infect. Immun.,65, 4488-4493). In this paper we report the chemical character-ization of the LOS from NTHi 9274 LOS. NTHi is capable of expressing a heterogenous population of LOS exhibited by multiple oligosaccharide (OS) epitopes. OSs released from the LOS of NTHi 9274 by mild acid hydrolysis were purified using Bio-Gel P4 gel permeation chromatography. The OSs were characterized by glycosyl composition analysis, glycosyl linkage analysis, nuclear magnetic resonance spectroscopy (NMR), fast atom bombardment mass spectro-metry (FAB-MS), matrix-assisted laser desorption time of flight mass spectro-metry (MALDITOF-MS), and tandem MS/MS. At least 17 different OS molecules were observed. These contained variable glycosyl residues, phosphate (P), and phospho-ethanolamine (PEA) substituents. These molecules contained either three, four, or five hexoses, and all contained four heptosyl residues. The four heptosyl residues consisted of one D,D-Hep and three L,D-Hep. Dephosphorylation of the OSs with aqueous 48% hydrofluoric acid (HF) reduced the number of molecules to about to seven; Hex(1)-(7)Hep(4)Kdo(1). Of these seven, Hex(2)Hep(4)Kdo(1), Hex(3)Hep(4)Kdo(1), and Hex(4)Hep(4)Kdo(1)were the major constituents. Thus, this NTHi LOS preparation is very heterogeneous, and contains structures different from those previously published for Haemophilus influenzae. The tandem MS/MS analysis and glycosyl linkage data suggest that the LOS oligosaccharides have the following structures where Hex is either a Glc or Gal residue.

Antigens, Bacterial↗
PubMed1995

Analysis of the OA1 gene reveals mutations in only one-third of patients with X-linked ocular albinism.

The locus for ocular albinism type 1 (OA1) has been assigned to the Xp22.3 region through both linkage and deletion mapping. The disorder was found to be genetically homogeneous, as all informative families showed convincing linkage data with markers on Xp22.3 and all identified deletions involved in the same region. The OA1 gene recently was cloned and several intragenic deletions were identified in affected individuals. We have characterized the genomic structure of the OA1 gene, which spans approximately 40 kb of genomic DNA and contains nine exons. A highly polymorphic dinucleotide repeat was identified in intron 1, that provides a useful tool for molecular diagnosis. Knowledge of the intron/exon boundaries allowed us to search for point mutations in patients' genomic DNA. All nine exons of the OA1 gene, as well as the 5' and 3' untranslated regions, were scanned for point mutations in PCR-amplified DNA from 60 OA1 patients. The mutations identified include: two frameshifts and a splice site mutation leading to truncated OA1 proteins; a deletion of a threonine codon at position 290; and four missense mutations,two of which involve amino acids located within putative transmembrane domains. Two of the mutations each occur in three apparently unrelated families, consistent with previous observations of a founder effect in OA1. Surprisingly, mutations were detected in only one-third of the patients (21 of 60) ascertained. We postulate that mutations not yet identified in either regulatory elements of the OA1 gene, or in other gene(s) located within the same chromosomal region, may be common cause of X-linked ocular albinism.

Albinism, Ocular↗
PubMed2006

Genetic variation in DTNBP1 influences general cognitive ability.

Human intelligence is a trait that is known to be significantly influenced by genetic factors, and recent linkage data provide positional evidence to suggest that a region on chromosome 6p, previously associated with schizophrenia, may be linked to variation in intelligence. The gene for dysbindin-1 (DTNBP1) is located at 6p and has also been implicated in schizophrenia, a neuropsychiatric disorder characterized by cognitive dysfunction. We report an association between DTNBP1 genotype and general cognitive ability (g) in two independent cohorts, including 213 patients with schizophrenia or schizo-affective disorder and 126 healthy volunteers. These data suggest that DTNBP1 genetic variation influences human intelligence.

Adult↗
PubMed1996

Declining induced abortion rate in Finland: data quality of the Finnish abortion register.

BACKGROUND: Induced abortion rates have declined in Finland since 1973. A possible explanation offered has been that of deteriorating data collection. METHODS: To assess the completeness of the Register, we compared the information from a consecutive sample of hospital records (N = 482) to the Finnish Abortion Register in 18 hospitals in three counties. A smaller consecutive sample (N = 345) was collected from the same hospitals to assess the validity of the Register information. RESULTS: Only five abortions (1 percent) found in the hospitals were not reported in the Abortion Register. A total of 95 percent of all the length of pregnancy (definition problems), the classification of the abortion procedure, and social class (out-of-date classifications). Furthermore, early complications were poorly reported. CONCLUSIONS: The data from the Finnish Abortion Register are a reliable source for monitoring trends in the abortion rate and its variation by subgroups, but are an unreliable source for the study of the medical aspects of induced abortion.

Abortion, Induced↗
PubMed2006

Structural effects of a covalent linkage between antithrombin and heparin: covalent N-terminus attachment of heparin enhances the maintenance of antithrombin's activated state.

We have produced a molecule comprising of permanently-activated covalently linked antithrombin and heparin (ATH). This study was designed to elucidate the covalent linkage point(s) for heparin on antithrombin and conformational properties of the ATH molecule. ATH was produced using Schiff base/Amadori rearrangement by incubating antithrombin with unfractionated heparin for 14 d at 40 degrees C. ATH was then digested using Proteinase K, and the heparin-peptide was reacted with NaIO4/NaBH4/mild acid to degrade the heparin moiety. Sequencing of the remaining peptide was performed by Edman degradation with linkage point confirmation by LC-MS. The degree of insertion of the reactive center loop (RCL) of antithrombin into the A-sheet of ATH was examined using synthesized antithrombin RCL peptides. Binding between the peptides and ATH, and the formation of ATH in the presence of the peptides were tested. CD was used to further examine the secondary and tertiary structures of ATH. The results suggest that heparin is conjugated to the amino terminal of antithrombin in the majority of ATH molecules, proximal to the previously determined heparin binding domain of antithrombin. From the linkage data, a model is proposed for the structure of ATH. Studies using the RCL peptides and CD analysis of ATH support this model.

Heparin↗
PubMed2006

A whole MEN1 gene deletion flanked by Alu repeats in a family with multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 is an autosomal dominant cancer syndrome characterized by pituitary, parathyroid and enteropancreatic endocrine tumors, which is caused by germline mutations of the tumor suppressor gene MEN1. In the case reported here, the patient had family with this disease whose germline MEN1 mutation was undetectable by conventional sequencing analysis. Further investigations involving polymorphism analyses, gene dose assay and nucleotide sequencing identified a large germline deletion of approximately 29 kilobase pairs spanning the whole MEN1 gene. The deletion was flanked by Alu repetitive sequences, suggesting unequal homologous recombination as the deletion mechanism. The polymorphism linkage data suggested that an asymptomatic son of the proband did not carry the family mutation. More direct evidence was obtained by gene dose assay and deletion-specific polymerase chain reaction, which demonstrated the normal MEN1 gene dosage and the absence of the deletion breakpoints in this asymptomatic subject and thus definitely excluded the possibility of disease predisposition.

Alu Elements↗