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At least 1,207 records · Page 67Linked to original sources
PubMed2001

Role of the serotonin transporter gene in the behavioral expression of autism.

The promoter polymorphism of the serotonin transporter gene (HTT, locus SLC6A4) is of special interest in autism given the well-replicated platelet hyperserotonemia of autism, treatment effects of serotonin reuptake inhibitors, and the role of serotonin in limbic functioning and neurodevelopment. Parent-offspring transmission of the long (l) and short (s) alleles of the deletion/insertion polymorphism in the HTT promoter region was examined in families of 71 children with autism using the transmission test for linkage disequilibrium (TDT). Transmission of HTT promoter alleles did not differ between probands with autism and their unaffected siblings. However, allelic transmission in probands was dependent upon severity of impairments in the social and communication domains, with greater s allele transmission in severely impaired individuals and greater l transmission in mild/moderately impaired individuals. This relationship between HTT promoter alleles and severity of autistic impairment was also seen when ratings of social and communication behaviors were compared across genotypes. The data indicate that HTT promoter alleles by themselves do not convey risk for autism, but, rather, modify the severity of autistic behaviors in the social and communication domains. The results require replication and, given the size of the groups and subgroups examined, must be considered still preliminary. The results suggest that future research on the genetics of autism should carefully assess each of the major behavioral domains and seriously consider the possible role of modifying loci.

Adolescent↗
PubMed2004

Targeted disruption of Nrf2 causes regenerative immune-mediated hemolytic anemia.

A basic leucine zipper transcription factor, NF-E2-related factor 2 (Nrf2), plays a critical role in the cellular defense mechanism by mediating a coordinate up-regulation of antioxidant responsive element-driven detoxification and antioxidant genes. Here, we report that targeted disruption of Nrf2 causes regenerative immune-mediated hemolytic anemia due to increased sequestration of damaged erythrocytes. Splenomegaly and spleen toxicity in Nrf2(-/-) mice raised a possibility of hemolytic anemia and splenic extramedullary hematopoiesis in Nrf2(-/-) mice. In support of this, hematology analysis revealed that Nrf2(-/-) mice suffer from anemia with abnormal red cell morphologies (i.e., Howell-Jolly bodies, acantocytes, and schistocytes). In addition, Nrf2(-/-) erythrocytes were more sensitive to H(2)O(2)-induced hemolysis, and erythrocyte-bound IgG levels were markedly increased in Nrf2(-/-) mice compared with Nrf2(+/+) mice. Because IgG bound to erythrocytes in the presence of oxidative damage in erythrocytes (regardless of Nrf2 genotype), these data support that Nrf2(-/-) erythrocytes have higher levels of damage compared with Nrf2(+/+) cells. Finally, Nrf2(-/-) mice showed increased levels of erythrocyte-bound IgG compared with Nrf2(+/+) mice after H(2)O(2) injection in vivo, suggesting that the decreased glutathione and increased H(2)O(2) render the Nrf2(-/-) mice more susceptible to toxicity. Taken together, these observations indicate that a chronic increase in oxidative stress due to decreased antioxidant capacity sensitizes erythrocytes and causes hemolytic anemia in Nrf2(-/-) mice, suggesting a pivotal role of Nrf2-antioxidant responsive element pathway in the cellular antioxidant defense system.

Anemia, Hemolytic, Autoimmune↗
PubMed2024

Age-induced changes in skeletal muscle mitochondrial DNA synthesis, quantity, and quality in genetically unique rats.

Mitochondrial genomic integrity is a key element of physiological processes and health. Changes in the half-life of the mitochondrial genome are implicated in the generation and accumulation of age-induced mitochondrial DNA (mtDNA) mutations, which are implicated in skeletal muscle aging and sarcopenia. There are conflicting data on the half-life of mtDNA, and there is limited information on how aging affects half-life in skeletal muscle. We hypothesized that skeletal muscle mtDNA synthesis rates would decrease with age in both female and male rats concomitant with changes in mtDNA integrity reflected in mtDNA copy number and mutation frequency. We measured mitochondrial genome half-life using stable isotope labeling over a period of 14 days and assessed mtDNA copy number and deletion mutation frequency using digital PCR in the quadriceps muscle of 9-month-old and 26-month-old male and female OKC-HET rats. We found a significant age-related increase in mtDNA half-life, from 132 days at 9 months to 216 days at 26 months of age in OKC-HET quadriceps. Concomitant with the increase in mtDNA half-life, we found an age-related increase in mtDNA deletion mutation frequency in both male and female rats. Notably, 26-month-old female rats had a lower mutation frequency than male rats, and there were no changes in mtDNA copy number with sex, age, or mitochondrial genotype. These data reveal several key findings: (1) mtDNA turnover in rat skeletal muscle decreases with age, (2) mtDNA half-lives in skeletal muscle are approximately an order of magnitude longer than what is reported for other tissues, and (3) muscle mtDNA turnover differs significantly from the turnover of other mitochondrial macromolecules including components of the mitochondrial nucleoid. These findings provide insight into the factors driving age-induced mtDNA mutation accumulation, which contribute to losses of mitochondrial genomic integrity and may play a role in skeletal muscle dysfunction.

Animals↗
PubMed2000

Genotype/phenotype correlation in carnitine palmitoyl transferase II deficiency: lessons from a compound heterozygous patient.

Carnitine palmitoyl transferase II deficiency, an inherited disorder of long-chain fatty acid oxidation, may result in either a mild form (muscle disease in adults) or a severe form (hepatocardiomuscular syndrome in infants). The difference in severity between these two forms is related to a difference in levels of residual carnitine palmitoyl transferase II activity and long-chain fatty acid oxidation and in genotypes. Few data are, however, available regarding compound heterozygotes for a 'mild' and a 'severe' carnitine palmitoyl transferase II mutation. We report on such a patient carrying both the 'mild' S113L substitution and the 'severe' Y628S mutation. The patient's clinical picture (cardiac arrest at 6 years) was markedly more serious than usually observed in S113L homozygotes, and suggested that 'mild'/'severe' compound heterozygosity makes patients at risk from life-threatening events. Palmitate oxidation and carnitine palmitoyl transferase II activity were lower in lymphocytes from the S113L/Y628S patient than in those from a S113L homozygote. Thus, assessment of carnitine palmitoyl transferase II mutations, long-chain fatty acid oxidation, and carnitine palmitoyl transferase II activity, may help in predicting the potential severity of the muscular form of carnitine palmitoyl transferase II deficiency.

Carnitine O-Palmitoyltransferase↗
PubMed2006

Does Pseudomonas aeruginosa colonization influence morbidity and mortality in the intensive care unit patient? Experience from an outbreak caused by contaminated oral swabs.

BACKGROUND: Contaminated oral swabs caused a nationwide monoclonal Pseudomonas aeruginosa outbreak involving 27 Norwegian hospitals. The aim of the study was to study the consequences on mortality and morbidity of the introduction of this P. aeruginosa strain to intensive care unit (ICU) patients. METHODS: Forty-four out of 96 patients admitted to the general ICU of Akershus University Hospital during the outbreak, ventilated for more than 24 h and with at least one microbiological sample, were included and followed until death or hospital discharge. All isolated P. aeruginosa strains were genotyped. Demographic data, admission diagnosis, Simplified Acute Physiology Score II (SAPS II), Sequential Organ Failure Assessment (SOFA) score, comorbidities, and antibiotics used in the first week were recorded. RESULTS: The outbreak strain was found in 18 patients (41%) of whom seven became infected. Median time to the first positive culture was 4 days. These 18 patients spent a significantly longer time on mechanical ventilation (P =0.03) and had a significantly higher hospital mortality, 55.5% vs. 19.2% (P =0.03), than non-colonized patients. The number of patients with severe underlying disease was significantly higher (P =0.01) and the decline in SOFA score was significantly slower in the pseudomonas group (P =0.02). Irrespective of colonization status, patients with severe underlying disease had a significantly higher mortality (58%) than those without (16%) (P =0.009). CONCLUSION: Use of contaminated oral swabs led to a high rate of early airways colonization. Patients with severe underlying disease were more likely to become colonized, but whether colonization has any influence on hospital mortality requires further study.

APACHE↗
PubMed2003

Exact test of Hardy-Weinberg equilibrium by Markov chain Monte Carlo.

The assumption of Hardy-Weinberg equilibrium (HWE) among alleles is of fundamental importance in genetic studies. There are numerous testing methods for it using genotype counts data. The exact test is used when the sample size is not large enough for asymptotic approximations. There are several numerical methods to carry out this test, such as complete enumeration, Monte Carlo and Markov chain Monte Carlo simulations. Complete enumeration is impractical in many applications, especially when the table counts are large. The Monte Carlo method is simple to use but still difficult when the table counts become large. The Markov chain Monte Carlo method, by sampling a sub-table each time, is suitable for this latter situation. Based on switches among a few (no more than four) cells, the existing Markov chain samplers are highly dependent and inefficient for large tables. Here we consider a new Markov chain sampling, in which a sub-table of user-specified size is updated at each iteration. The resulting chain is less dependent, and the sampling is flexible and efficient. The conventional test for HWE is based on a few test statistics, such as the likelihood and the chi-squared statistic. To expand the family of test statistics, we consider a class of divergence measures for the departure of HWE. Examples are given as illustrations.

Alleles↗
PubMed2004

Physiological cost of tolerance to toxicants in the European flounder Platichthys flesus, along the French Atlantic Coast.

Physiological and genetic responses of flounder Platichthys flesus populations were investigated along the French Atlantic Coast in one moderately contaminated estuary (Ster) and three contaminated estuaries (Seine, Loire and Gironde). The focus of this study was to explore the relationship between stress resistance and energetic trade-offs, in order to detect possible differential physiological capacities or performances between individuals carrying particular alleles or genotypes (allozyme data) characterised as "tolerant" or "sensitive". A general reduction of the relative fecundity, the growth rate and the condition factor was highlighted in contaminated fish populations, suggesting that survival in such polluted systems implies energetic costs for fish thus reducing the energy available for particular functions. A lower observed heterozygosity was also detected in contaminated populations with respect to the Ster, suggesting a general decrease in genetic variability in response to chemical stress (with an exception for the Seine estuary). This study confirmed the previously detected relationship between PGM 85, AAT1 95 alleles and reduced DNA damage in contaminated fish [Marchand, J., Tanguy, A., Laroche, J., Quiniou, L., Moraga, D., 2003. Responses of European flounder Platichthys flesus populations to contamination in different estuaries along the Atlantic coast of France. Mar. Ecol. Prog. Ser. 260, 273-284] and furthermore suggested that, reduced fecundity and condition factor associated to the individuals carrying the previous alleles, were also reflecting the cost of resistance to stress in polluted populations. The cost of tolerance to stress as well as the high gene flow from neighbouring populations less exposed to contamination may explain the apparently moderate increase of the suspected "tolerant" alleles in contaminated flounder populations.

Analysis of Variance↗
PubMed2002

Assessment of a difference in ALDH2 heterozygotes and alcoholic liver injury.

We have speculated that the degree of liver dysfunction in alcoholic liver disease with ALDH2*1/2*2 may be less pronounced than that with ALDH2*1/2*1. In the present study, outpatients with alcoholic liver injury were examined for ALDH2 genotype and biochemical data. The number of patients was 29 cases of nonspecific changes, 16 cases of fatty liver, 5 cases of liver fibrosis, and 44 cases of liver cirrhosis. Biochemical data were evaluated with ALDH2 heterozygotes data obtained by PCR-SSCP. The ALDH2*1/2*1 and ALDH2*1/2*1 genotypes accounted for 90% and 10%, respectively. As for ALDH2*1/2*2, there were three patients with nonspecific changes, three with fatty liver, one with liver fibrosis, and two with liver cirrhosis. In alcoholic liver disease patients, when the ALDH2*1/2*2 genotype was compared with the ALDH2*1/2*1 genotype with biochemical data, the gamma-GTP value in patients with ALDH2*1/2*2 was significantly higher than with ALDH2*1/2*1 ( < 0.005). When the frequency of ALDH2 genotype was determined in patients with alcoholic liver injury, ALDH2 heterozygotes accounted for 15% for the non-cirrhosis group, and 5% for the cirrhotic group. When a relationship between the amount of ethanol intake and biochemical data were determined in patients with alcoholic liver injury who have ALDH2 heterozygotes, the glutamic oxaloacetic transaminase (GOT) and gamma-GTP values were significantly higher at an ethanol intake amount of ethanol more than 100 g per day than intake less than 100 g per day ( < 0.05). The alcoholic patients with ALDH2*1/2*2 drink a slight amount of ethanol, the liver injury is found to be stronger than those with ALDH2*1/2*1 when they drink more than 100 g ethanol per day.

Aldehyde Dehydrogenase↗
PubMed2002

Efficacy and toxicity of antiretroviral therapy using 4 or more agents: application of a strategy for antiretroviral management in human immunodeficiency virus-infected children.

OBJECTIVE: To characterize the long-term tolerance and virologic efficacy of combination antiretroviral therapy consisting of 4 or more agents in a clinical setting. METHODS: An observational review of 36 children infected with human immunodeficiency virus 1 (HIV-1) treated with 4 or 5 antiretroviral agents in 2 university hospital clinics between April 1, 1996, and October 31, 2000. Highly active antiretroviral therapy regimens were chosen with regard to the child's past antiretroviral exposure or results of genotypic resistance data. Plasma HIV-1 RNA levels were monitored weekly to monthly after initiation of highly active antiretroviral therapy, and adherence efforts were actively supported and monitored. MAIN OUTCOME MEASURE: Number of children with undetectable plasma HIV-1 RNA levels at longest follow-up. RESULTS: Four- or 5-drug highly active antiretroviral therapy reduced plasma HIV-1 RNA levels to less than 50 copies/mL in 32 (89%) of 36 children. After a median of 28.7 months of observation, 28 children (78%) remained at this level of suppression. Adverse reactions were limited to mild neutropenia and mild transient or persistent elevations in alanine aminotransferase levels in 11% of children. CONCLUSIONS: Treatment with 4 or 5 antiretroviral agents was well tolerated in HIV-1-infected children and resulted in a high degree of viral suppression, even in children with previous antiretroviral drug experience.

Antiretroviral Therapy, Highly Active↗
PubMed2000

Three probands with autistic disorder and isodicentric chromosome 15.

We have identified three unrelated probands with autistic disorder (AD) and isodicentric chromosomes that encompass the proximal region of 15q11.2. All three probands met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition [DSM-IV; American Psychiatric Association, 1994], and International Classification of Diseases ( ICD-10) diagnostic criteria for AD, confirmed with the Autism Diagnostic Interview -Revised (ADI-R). Chromosome analysis revealed the following karyotypes: 47,XX,+idic(15)(q11.2), 47,XX, +idic(15) (q11.2), and 47,XY,+idic(15)(q11.2). Haplotype analysis of genotypic maker data in the probands and their parents showed that marker chromosomes in all three instances were of maternal origin. Comparison of the clinical findings of the three AD probands with case reports in the published literature (N = 20) reveals a clustering of physical and developmental features. Specifically, these three probands and the majority of reported probands in the literature exhibited hypotonia (n = 13), seizures (n = 13), and delayed gross motor development (n = 13). In addition, clustering of the following clinical signs was seen with respect to exhibited speech delay (n = 13), lack of social reciprocity (n = 11), and stereotyped behaviors (n = 12). Collectively, these data provide further evidence for the involvement of chromosome 15 in AD as well as present preliminary data suggesting a clustering of clinical features in AD probands with proximal 15q anomalies.

Adolescent↗
PubMed1994

Follow-up of a report of a potential linkage for schizophrenia on chromosome 22q12-q13.1: Part 2.

A collaboration involving four groups of investigators (Johns Hopkins University/Massachusetts Institute of Technology; Medical College of Virginia/The Health Research Board, Dublin; Institute of Psychiatry, London/University of Wales, Cardiff; Centre National de la Recherche Scientifique, Paris) was organized to confirm results suggestive of a schizophrenia susceptibility locus on chromosome 22 identified by the JHU/MIT group after a random search of the genome. Diagnostic, laboratory, and analytical reliability exercises were conducted among the groups to ensure uniformity of procedures. Data from genotyping of 3 dinucleotide repeat polymorphisms (at the loci D22S268, IL2RB, D22S307) for a combined replication sample of 256 families, each having 2 or more affected individuals with DNA, were analysed using a complex autosomal dominant model. This study provided no evidence for linkage or heterogeneity for the region 22q12-q13 under this model. We conclude that if this region confers susceptibility to schizophrenia, it must be in only a small proportion of families. Collaborative efforts to obtain large samples must continue to play an important role in the genetic search for clues to complex psychiatric disorders such as schizophrenia.

Adult↗
PubMed2006

Further phenotypic and genetic variation in ADULT syndrome.

ADULT (Acro-dermato-ungual-lacrimal-tooth) syndrome is characterized by ectrodactyly, syndactyly, fingernail and toenail dysplasia, hypoplasia of the breast and nipple, excessive freckling, lacrimal duct atresia, frontal alopecia, primary hypodontia, and/or early loss of permanent teeth. It is a rare autosomal dominant disorder which has been linked to mutation in the p63 gene. The p63 gene has been described in five overlapping limb malformation syndromes including the EEC syndrome (ectodermal ectrodactyly clefting). We report on the first case of ADULT syndrome of a mother and daughter with a new mutation R227Q in exon 6 of the p63 gene. This has not been previously associated with ADULT syndrome but only seen in EEC. In addition to the previously reported features of ADULT syndrome this report also describes some additional findings including hyperextensibility at the distal interphalageal joints, bilateral thumb duplication, bifid toenails, symptoms of urinary retention, vesicoureteric reflux, prominent ears, conductive hearing loss, and an overgrowth of a patch of hair in the midline of the neck. This report expands the knowledge of genotype-phenotype data on the p63 gene and suggests there may be a considerable overlap between the EEC syndrome and the ADULT syndrome.

Abnormalities, Multiple↗
PubMed2003

Association of the C766T polymorphism of the low-density lipoprotein receptor-related protein gene with Alzheimer's disease.

The low-density lipoprotein receptor-related protein (LRP) is one of the most important cholesterol receptors in the brain. Gene variation of its ligand, apolipoprotein E, is a major genetic risk-factor for Alzheimer's disease (AD). The C-allele of the silent C766T polymorphism in exon 3 of the LRP gene might be associated with AD, however, results are conflicting and thus discussed controversially. Consequently, we compared the prevalence of this polymorphism in a homogenous cohort of patients with AD and control subjects. We found that carriers of a C-allele were at lower risk of AD; in agreement with this observation, AD patients who were carriers of a C-allele presented with a later age at onset of the disease than carriers of the TT genotype. These data suggest that LRP polymorphism influences the risk as well as the age at onset of AD. Our results contrast with other studies which described the C-allele to be a risk-factor for AD, but are in line with a recent publication on the effect of LRP polymorphism on longevity and on the risk for coronary artery disease. Further research on LRP polymorphisms is needed to evaluate their effects on the risk of AD, on coronary artery disease and on longevity.

Alzheimer Disease↗
PubMed1997

Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease.

To assess the relationship between dementia, neuronal loss, and neuropathological findings in Alzheimer's disease (AD), we counted the number of neurons, senile plaques, and neurofibrillary tangles in a high-order association cortex. We studied the superior temporal sulcus of 34 individuals with AD and 17 nondemented control subjects, using statistically unbiased, stereological counting techniques. The number of superior temporal sulcus neurons in nondemented control subjects was stable across the sixth to ninth decades. In AD, more than 50% of the neurons were lost. Both neuronal loss and neurofibrillary tangles increased in parallel with the duration and severity of illness, but the amount of neuronal loss exceeded by manyfold the amount of neurofibrillary tangles accumulated. In contrast to the correlation between neurofibrillary tangles and neuronal loss, the number of senile plaques and the percentage of the superior temporal sulcus that was covered by Abeta (amyloid burden) were not related to neuronal loss, number of neurofibrillary tangles, or duration of disease. Neither the amount nor the rate of neuronal loss in the superior temporal sulcus in AD correlated with apolipoprotein E genotype. These data suggest that neuronal loss in association areas such as the superior temporal sulcus contributes directly to cognitive impairment in AD.

Aged↗
PubMed2005

Bayesian models for population-based case-control studies when the population is in Hardy-Weinberg equilibrium.

Association analysis of genetic polymorphisms has been mostly performed in a case-control setting with unrelated affected subjects compared with unrelated unaffected subjects. In this paper, we present a Bayesian method for analyzing such case-control data when the population is in Hardy-Weinberg equilibrium. Our Bayesian method depends on the informative prior which is the retrospective likelihood based on historical data, raised to a power a. By modeling the retrospective likelihood properly, different prior information about the studied population can be incorporated into the specification of the prior. The scalar a is a precision parameter quantifying the heterogeneity between current and historical data. A guide value for a is discussed in this paper. The informative prior and posterior distributions are proper under very general conditions. Therefore, our method can be applied in most case-control studies. Further, for assessing gene-environment interactions, our approach will naturally lead to a Bayesian model depending only on the case data, when genotype and environmental factors are independent in the population. Thus our approach can be applied to case-only studies. A real example is used to show the applications of our method.

Bayes Theorem↗
PubMed2000

Mutations of the core promoter and response to interferon treatment in chronic replicative hepatitis B.

In chronic replicative hepatitis B the significance of mutations in the basic core promoter (BCP), core upstream regulatory sequences (CURS) and negative regulatory element (NRE) for response to interferon (IFN) is unknown. A sequence analysis of the NRE, CURS, BCP, and precore region was performed from sera of 96 patients with chronic replicative hepatitis B (64 hepatitis B e antigen [HBeAg]-positive patients and 32 HBeAg-negative patients) treated with alfa-IFN (IFN-alpha). The overall sustained response (SR) rate to IFN was 30% with no significant difference between HBeAg-positive and HBeAg-negative patients. IFN responsiveness correlated to hepatitis B virus (HBV)-DNA levels, hepatitis B surface antigen (HBsAg) levels, the number of mutations in the complete BCP, especially nucleotide (nt) region 1753 to 1766 and mutations at nt 1762 and 1764. In HBeAg-positive hepatitis, SR to IFN was associated with a high number of mutations in the BCP (P <.04) and nucleotide region 1753 to 1766 (P <.015) as well as mutations at nucleotide 1764 (P <.007). In HBeAg-negative hepatitis, SR to IFN correlated with a low number of mutations in the BCP (P <.04) and nucleotide region 1753 to 1766 (P <.02) and a wild-type sequence at nt 1764 (P <.003). Prediction of IFN response was possible on the basis of nt 1764 in 77% of HBeAg-positive patients and 78% of HBeAg-negative patients. IFN response did not correlate with the occurrence of the 1896 mutation, mutations in the CURS or NRE, disease duration, ethnic origin of the patient, alanine transaminase (ALT) levels and HBV genotype. Our data suggest that HBV genome mutations located within the BCP are determinants of a response to IFN therapy.

Adult↗
PubMed2002

Interaction between a single nucleotide polymorphism in the alcohol dehydrogenase 3 gene, alcohol consumption and oral cancer risk.

We investigated effects on oral cancer (OC) risk of an interaction between a single nucleotide polymorphism (SNP) in the alcohol dehydrogenase 3 (ADH3) gene and alcohol consumption levels using a hospital-based study of 93 cases and 99 controls conducted in Athens, Greece. This SNP affects ethanol metabolism in vitro and appeared to interact with alcohol consumption in a previous OC study. We also evaluated a SNP in CYP2E1, another gene involved in ethanol metabolism, reported to be associated with OC risk in a European population. Data on genotypes and risk factors obtained from interviews were analyzed using multivariate logistic regression, accounting for potential confounders. No overall (marginal) association was found between OC risk and ADH3 genotypes. An interaction between ADH3 genotypes and alcohol consumption levels, however, was suggested. In non-drinkers, the ADH3(1-1) genotype has higher risk than ADH3(1-2) or ADH3(2-2) genotypes, but for subjects consuming alcohol, lower risk was observed for ADH3. We fit a logistic regression model to estimate the increase in OC risk associated with each alcohol drink consumed per week. We estimated that OC risk increased by 31.5% per drink/week for the ADH3(2-2) genotype, 4.1% for the ADH3(1-2) genotype and 1.6% for the ADH3(1-1) genotype. Evidence of genotype-environment interaction was suggestive (p = 0.048, Wald chi p = 0.145, likelihood ratio). This finding is opposite to that reported for a population in Puerto Rico, where the ADH3(1-1) genotype seemed more sensitive to ethanol exposure. In Greece, genetic variation at the CYP2E1 SNP is almost entirely absent, with only 1 case and 1 control heterozygous for the variant. By contrast, in a population in France where an OC association was reported, the frequency of CYP2E1 heterozygotes was 5% in controls and 9% in OC cases. These findings illustrate the importance of replicating SNP associations both within and between different racial and ethnic groups and geographic regions.

Alcohol Dehydrogenase↗
PubMed2004

Prenatal diagnosis of DMD in a female foetus affected by Turner syndrome.

OBJECTIVES: We report on a prenatal diagnosis of DMD complicated by a 45,X karyotype that was revealed only in the chorionic villus long-term culture. METHODS: Cytogenetic investigations were performed on both short-term (STC) and long-term cultures (LTC) of the chorionic villus sample. Familial segregation was performed using a panel of intragenic polymorphic markers, and multiplex PCR was used to characterize exonic deletion. RESULTS: Investigations performed for sex determination after STC of the chorionic villus sample showed a normal karyotype 46,XX, while the karyotype performed after LTC revealed a homogeneous monosomy X. Cytogenetic analysis performed on amniotic fluid cells showed 45,X/46,XX mosaicism. Familial segregation analysis for DMD showed loss of heterozygosity for the STR49 marker in the DNA of the proband, her mother and the foetus. Dystrophin gene analysis on the 45,X cells led to the identification of a deletion of exon 50. CONCLUSIONS: The report described a rare situation of monosomy X associated with a DMD genotype. The data confirmed the DMD carrier status of the proband and her mother and indicated that the foetus had a high risk to combine a Turner phenotype and DMD. This study illustrated the potential risk of using short-term culture of villi as the only source of biological material for prenatal diagnosis.

Diagnosis, Differential↗