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Results for “multifactorial inheritance”

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PubMed1993

Frontonasal dysplasia, lipoma of the corpus callosum and tetralogy of Fallot.

A 6-year-old Egyptian boy with frontonasal dysplasia (FND) and lipoma of the corpus callosum associated with tetralogy of Fallot is reported. The main features were severe hypertelorism, downward slanted palpebral fissures, bilateral epicanthal folds, a grossly deformed nose with notched alae nasi, absent nasal tip and long philtrum. A computerized tomography (CT) scan of the brain showed cerebral atrophy and lipoma of the corpus callosum. While marked neurological symptoms have been reported in cases with lipoma of the corpus callosum in the absence of FND, the present case and previous reports showed minor neurological alterations when lipoma of the corpus callosum was associated with FND. From the findings in this case and previous reports, it is possible to conclude that lipoma of the corpus callosum associated with FND is always located in the anterior part of the corpus callosum. The etiology of FND remains uncertain. While multifactorial inheritance has been proposed, parental consanguinity with young parental age in the present case cannot exclude autosomal recessive inheritance.

Abnormalities, Multiple↗

PubMed2004

Genetic analysis of lethal congenital malformations causing perinatal mortality at Nizwa Hospital, Oman.

An analysis of lethal congenital malformations (LCM) - which contributed to perinatal mortality at Nizwa Hospital, Oman - is presented for a 10-year period from January 1993 through December 2002. Single gene, chromosomal or multifactorial inheritance accounted for 86.1% of the cases. LCM-related perinatal deaths were higher in Omani, compared to those in non-Omani births (p < 0.001). This could possibly be attributed to high consanguinity, low female literacy and high fertility rates in the Omani population. Forty per cent of LCM-related perinatal deaths in the study had potential options for prevention. Integration of a community-based genetic service into the existing health-care delivery system is suggested.

Cause of Death↗

PubMed1979

The use of multiple thresholds and segregation analysis in analyzing the phenotypic heterogeneity of multifactorial traits.

(1) Three models based on multifactorial inheritance are introduced to account for phenotypic heterogeneities. These models are used to determine whether subforms of a triat are: (a) different degrees of the same process, (b) non-familial environmental variants of the same process, and (c) independently transmitted processes. (2) The parameters of each model consist of two population prevalences and either one, two, or three correlation coefficients which reflect the three hypotheses given above. The models are formulated so that a likelihood ratio test may be performed to discriminate between them. (3) The following types of analyses are described: (a) analysis of prevalence data with separate population prevalence estimates, (b) analysis of prevalence data with the proband a parent with specified spouse, (c) analysis of prevalence data with the proband an offspring with specified parents, and (d) the full segregation distribution of families using Complex Segregation Analysis. (4) When compared with the Analysis of Prevalences, Complex Segregation Analysis has the following advantages: (a) the number of degrees of freedom for parameter estimates is greater and separate estimates of the population prevalences are not necessary, (b) standard errors of the parameters are smaller, and (c) the power to discriminate models is increased. (5) Phenotypic heterogeneities such as age of onset, severity, and sex effect can be more completely understood by the methods of analyses described above. The nosology of familial disorders can also be clarified, and environments relevant to the transmission of the trait can be detected. This approach is particularly suitable for the analysis for behavioural traits since it does not require the assumption that environmental effects common to relatives be ignored. (6) Finally, our experience indicates that incorporating both prevalence and pedigree data into a single analysis decreases the time required to perform the analysis.

Environment↗

PubMed1981

The indicence of severe pre-eclampsia amongst mothers and mothers-in-law of pre-eclamptics and controls.

In order to distinguish between a maternal, fetal or maternal and fetal genetic predisposition towards severe pre-eclampsia, the first pregnancies of 158 mothers and 160 mothers-in-law of pre-eclamptic women and of matched controls were analysed. Fourteen per cent of mothers of pre-eclamptics were found to have had severe pre-eclampsia, confirming previous suggestions that the condition "runs in families', in contrast to only a 3% incidence amongst mothers of controls. The incidence in mothers-in-law of both pre-eclamptics and controls was 4%, in full agreement with a maternal genotype hypothesis and suggesting that the fetal genotype plays, at most, only a minor role in the aetiology of severe pre-eclampsia. The data are in agreement with the hypothesis that a single recessive gene acting in the mother could be responsible for severe pre-eclampsia, but multifactorial inheritance is not ruled out. Mild pre-eclampsia showed no such familial tendency, indicating that the mild and severe forms of pre-eclampsia may represent separate pathological entities.

Female↗

PubMedDate not supplied

Neural tube defects: a primary prevention role for nurses.

Neural tube defects are among the most common and serious birth defects. Most of these defects are caused by multifactorial inheritance. Research over the past decade has led to advances in understanding the etiology of these congenital anomalies. Folic acid has been shown to reduce the risk of first-time occurrence of neural tube defects as well as recurrent risk. Other genetic and environmental factors are under investigation. In this article, the nurse's role in the primary prevention of these birth defects is described.

Female↗

PubMed1988

Immunological studies in focal epilepsy.

Serum immunoglobulins, T-lymphocyte subsets and HLA investigations were carried out in 24 patients with focal, mainly temporal lobe, epilepsy and in 30 of their first degree relatives. The mean serum level of IgA was significantly decreased in the epileptic probands compared with controls. In the relatives, there was a significant decrease in mean IgM levels. The epileptic group had significantly fewer circulating T4 "helper" lymphocytes (absolute and percent) and an increased percentage of T8 "cytotoxic"/"suppressor" lymphocytes than the controls. The effect of antiepileptic drug treatment on these results is discussed. The frequencies of 63 HLA specificities determined were not significantly different in probands compared with controls. Among 5 of the most commonly occurring haplotypes there was a lower frequency of the haplotype A1,B8 in epileptic probands, which is in accordance with an earlier study on benign focal epilepsy in children. The immunological findings support the possibility that focal epilepsy may be linked to a genetically dependent immune dysregulation. The latter may contribute to the variability underlying the multifactorial inheritance of the epilepsies.

Adolescent↗

PubMed1998

Clinical significance of morphologic and genetic examination of spontaneously aborted embryos.

PROBLEM: In families with a history of multiple pregnancy losses, the prognosis of future pregnancies is critically dependent on recognizing an accurate pathogenesis of pregnancy loss. METHOD OF STUDY: Morphological and genetic evaluation of products of conception provides necessary information for clinicians. Modern molecular cytogenetic techniques such as in situ hybridization and comparative genomic hybridization allow cytogenetic diagnosis even when aborted tissues are nonviable. RESULTS: Correlation of morphological and cytogenetic findings allows distinction between developmental defects associated with chromosomal syndromes and other pathogenesis such as environmental teratogens, and Mendalian or multifactorial inheritance. CONCLUSION: Pathologists have the responsibility of ensuring that the answers to questions, such as why the failure occurred or whether there is any increased chance of having an abnormal liveborn infant in a future pregnancy, are obtained and that the information is communicated to the parent's obstetrician, geneticist, and family physician.

Abortion, Habitual↗

PubMed1992

Immunoglobulin and HLA-DP genes contribute to the susceptibility to juvenile dermatitis herpetiformis.

HLA-DQ genes and gluten diet are the main factors involved in the pathogenesis of Dermatitis Herpetiformis (DH), as well as Coeliac Disease (CD). However other genetic factors are probably relevant, since about 10% of the patients with DH and CD lack the DQA1*0501/B1*0201 heterodimer while the majority of individuals presenting this genotype and also being exposed to gluten diets did not suffer from these diseases. To evaluate the role of other genes, 36 Northern Italian children with DH were analysed for DNA polymorphisms at HLA-DP and immunoglobulin (Ig) heavy chain loci. DPA1*0201 and DPB1*1301 frequencies were higher in patients than in controls (Pc = 0.0357 and Pc = 0.0273). With respect to immunoglobulin heavy chain restriction fragment length polymorphisms (RFLP), the 4.6 kb SacI RFLP at the switch alpha 2 gene was more frequent in patients (0.13) than in controls (0.019; Pc = 0.036). Moreover, rare alleles or duplications in the switch regions occurred more frequently in the patients than in the controls. These results support the hypothesis of a multifactorial inheritance of DH, the HLA and Ig constant heavy chain genes being some of the loci contributing to the susceptibility. In accordance with previous CD studies, these data also confirm that DP subregion is probably involved in the pathogenesis of DH.

Adolescent↗

PubMed1985

Wiedemann-Beckwith syndrome in one of monozygotic twins.

A pair of monozygotic twins discordant for Wiedemann-Beckwith syndrome is described. The probability of monozygosity is 0.995. This observation suggests that the syndrome is unlikely to be under single gene control and genetic counselling should be based on multifactorial inheritance.

Beckwith-Wiedemann Syndrome↗

PubMed1975

Two family studies on congenital dislocation of the hip after early orthopaedic screening Hungary.

Two family studies involving 1767 and 379 index patients in Budapest and Bekes county, respectively, were undertaken to examine the effect of early orthopaedic screening on the recurrence risk of congenital dislocation of the hip. About 14%, 2.1-2.3%,1.2-1.4%, and 4.7-6% of sibs, parents, uncles and aunts, and cousins, respectively, had congenital dislocation of the hip in these two surveys. The recurrence risks were eight-fold and four-fold higher in brothers and sisters, four times higher in parents, 2.5-fold higher in uncles and aunts, and 2.0-2.5 times higher in cousins, respectively, than in the general population. This family pattern seems to fit best with a model of polygenic-multifactorial inheritance. In earlier studies higher recurrence risks were found. These may be explained by the change of diagnosis due to early orthopaedic screening which may increase the possibility of over diagnosis and the treatment of mild cases which previously recovered spontaneously.

Adult↗

PubMed1976

A family study of coarctation of the aorta.

Families of 100 patients with coarctation of the aorta and 50 controls for age, sex, and social status were studied to assess the influence of genetic and environmental variables in the aetiology. A tendency to familial aggregation of the condition and other congenital heart defects compatible with multifactorial inheritance was discerned. Recurrence risk for sibs is approximately 1 in 200 for coarctation of the aorta, and 1% for any form of congenital heart defect. The heritability of coarctation is estimated at 58%. The tendency for other non-cardiac defects to occur in the patients with coarctation does not appear in their sibs and is not so pronounced as in some other congenital heart conditions. Of the several environmental variables examined, there was no definitive association with any other than season of birth, which implies a possible association with maternal infection; there is also a suggestion of a paternal age effect, but these require investigation in a prospective survey.

Abnormalities, Multiple↗

PubMed1987

Frontonasal dysplasia associated with tetralogy of Fallot.

Three children with frontonasal dysplasia associated with tetralogy of Fallot are reported. All cases had true hypertelorism and a median nasal groove with absence of the nasal tip. There was no mental deficiency. The facial anomaly is a sporadic, non-genetic interference of the normal development of the face. This is the first report of frontonasal dysplasia associated with a cardiac defect. Multifactorial inheritance of this syndrome is proposed.

Abnormalities, Multiple↗

PubMed2000

Genetics of club foot in Maori and Pacific people.

The role of major gene and multifactorial inheritance in the aetiology of club foot in the New Zealand Polynesian population was studied using 287 New Zealand Maori and Pacific club foot families. The club foot family data were analysed by complex segregation analysis under the mixed model using the computer program POINTER. This analysis shows that the best genetic model for club foot in this population is a single dominant gene with a penetrance of 33% and a predicted gene frequency of 0.9%. These data provide a scientific foundation for molecular studies in the Maori and Polynesian population to identify putative club foot genes.

Alleles↗

PubMed1976

Recurrence risks in children having one parent with a congenital heart disease.

The risk of recurrence of a congenital cardiovascular malformation in a child having one parent with congenital heart disease has been determined for each of the seven most common anomalies presently compatible with survival to reproductive age. The range of risk is 2.5% to 4.3% depending on the lesion. This is within the range of expectation for the model of multifactorial inheritance previously used to predict recurrence in other first-degree relatives of probands (siblings and parents) with congenital heart disease. The cardiovascular abnormality occurring in the child was most often the same as in the parent or was a closely related variant of it.

Adult↗

PubMed2006

From genetics to epigenetics.

In the post human-genome area, the challenge is to derive details of heritable variation in relation to how human variation reflects adaptation to the different environments. Heterozygote advantage represents a superior genetic adaptation presumably explaining the presence of the allele at frequencies above those to be expected from a simple replacement of a homozygous lethal allele by mutation alone (Saugstad 1977a, 1975b, 1972). Mean birthweight of unaffected offspring of parents heterozygous for the phenylketonuria (PKU) allele averaged significantly above mean weight of all Norwegian births, rendering unaffected offspring more viable at birth and thus improving the chance for survival of the allele. A successful adaptation requires natural selection acting on that part of the body that makes a difference in survival. Skin colour variation is such a successful adaptation, for the North as opposed to the dark skins of the equator. Human Evolution in Africa and subsequent adaptations have enabled human survival all over the world with highly different light intensity (Jablonski & Chaplin 2000). That continuous variables, height, pubertal age and brain development, are multifactorially inherited and affected by epigenetic factors, was nicely demonstrated in the increase in height in Norway 1860-1960 with at the same time a reduction in pubertal age by 4yrs which may have affected the final stage in brain development. This created an increased need for brain food, N-3, to secure optimal brain function. Body growth is not brain growth. Given that the consumption of brain food (N-3) has declined to 20% only of the level 100yrs ago, what disorders are to be expected with an N-3 dietary deficit: in pregnancy, infancy and later in life? In this paper I discuss the significance of prepubertal selective pruning of excitatory synapses compared to delayed pruning and suggest relationships with brain disorders.

Adaptation, Physiological↗

PubMed2026

Combinatorial multiomic analysis from a pedigree of Sox10Dom Hirschsprung mice identifies multiple high confidence candidate modifiers of Enteric Nervous System development.

Hirschsprung disease (HSCR) is characterized by absence of enteric ganglia (aganglionosis) along variable lengths of the distal intestine. This disorder results from deficient colonization of fetal intestine by enteric neural crest-derived cells (ENCDCs). HSCR exhibits complex, multifactorial inheritance with penetrance and severity varying widely even within families. SOX10 is among causal genes that predispose to aganglionosis. Yet, how gene interactions influence severity of HSCR aganglionosis is not understood. Prior mapping of aganglionosis modifiers was achieved in a standard F1-intercross utilizing the Sox10Dom HSCR mouse model. Here we deploy a novel strategy of genotyping an extended pedigree pedigree of Sox10Dom mice on a mixed genetic background. GWAS in this pedigree points to novel aganglionosis modifier intervals with replication and refinement of prior modifier regions. Complementary omics analysis of the developing Enteric Nervous System (ENS) enabled identification of multiple high-priority candidate genes within these modifier intervals based on gene expression, chromatin accessibility, and presence of conserved SOX10 binding motifs. We implemented a prioritization pipeline for ranking potential modifiers that generated candidate lists including several well-known for effects on ENS development as well as multiple novel genes. Among the novel genes, Dach1 ranked as a top priority candidate gene for modifying migration of ENCDCs and thus influencing aganglionosis severity. The results identify genome intervals with intrinsic genes that are logical candidates for modifying Sox10Dom aganglionosis severity. We also note that several human orthologs to aganglionosis modifier candidate genes are within linkage disequilibrium blocks containing genetic variants associated with human gut motility disorders, which offers opportunity for gaining biological insight into human HSCR severity.

Animals↗

PubMed2003

Proteome analysis of diseased joints from mice suffering from collagen-induced arthritis.

Strains of mice that are susceptible to autoimmunity have provided experimental models to analyze the molecular basis for the complex multifactorial inheritance of human autoimmune disease. In this study proteins associated with collagen-induced arthritis (CIA) in mice were experimentally identified using a global proteomics approach. Two-dimensional gels of proteins from inflamed and non-inflamed joints showed a distinguished protein profile visualizing about 530 Coomassie-stained protein spots in the pH 4-7 range. A total of 76 spots were identified by peptide mass fingerprinting with good confidence. They included proteins of cytoskeletal origin, chaperones, enzymes and also some signal transduction molecules. Comparison to gels from non-inflamed paws pointed to proteins that were differentially expressed between the control and diseased state. Ferritin light chain and antioxidant protein 2 were slightly more abundant, lymphoid enhancer binding factor 1 slightly, but significantly, less abundant in inflamed paws. Fourteen of the identified proteins were the products of genes that had increased transcript levels in the diseased state. However, on the protein level no significant differences were found in comparison to the controls. This study provides us with the framework for more detailed approaches to understanding the complex disease arthritis that go beyond global proteomics.

Amino Acid Sequence↗

PubMed2005

Concordant occipital encephalocele in monoamniotic twins.

Anomalies occur with a greater frequency in twin gestations. Due to its multifactorial inheritance, twins are usually discordant for encephalocele. We present a case of monoamniotic twins concordant for occipital encephalocele and discordant for lung and cord anomalies. Ultrasonographic examination at 17 weeks' gestation revealed occipital encephalocele in both fetuses. The maternal serum level of alpha-fetoprotein was increased. Fetal autopsy revealed occipital encepaholocele in both twins and right pulmonary hypoplasia and one umbilical artery in one sibling. Monoamniotic twins concordant for encephalocele occur with extreme rarity. To the best of our knowledge, monoamniotic twins concordant for this neural tube defect have not been previously reported.

Adult↗