Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Inheritance Patterns”

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 163 records · Page 9Linked to original sources
PubMed1992

Evidence for paternal imprinting in familial Beckwith-Wiedemann syndrome.

A previously unreported family in which seven members in two generations have Beckwith-Wiedemann syndrome (BWS) is documented. Paternal imprinting of the gene responsible for BWS is involved as the mechanism responsible for the aberrant inheritance pattern in this kindred. A review of published reports showed 27 previously published pedigrees with two or more affected subjects with BWS. Paternal imprinting would explain the non-mendelian inheritance of BWS in all but four kindreds. The latter families are examined in more detail and in only one example is the evidence against imprinting totally unexplained.

Beckwith-Wiedemann Syndrome↗
PubMed1986

Intellectual and cognitive function in adults with myotonic muscular dystrophy.

Intellectual and cognitive function was studied in 43 patients (21 men and 22 women) with myotonic muscular dystrophy (MMD). The inheritance distribution was 18 paternal, 10 maternal, and 15 unknown. All patients received the Wechsler Adult Intelligence Scale-Revised, the Wechsler Memory Scale, the Halstead-Reitan Neuropsychological Test Battery, and the Aphasia Screening Test. Significantly lower scores (p less than 0.05) were found on all intellectual and cognitive impairment tests in both men and women of the maternal inheritance MMD subgroup, compared with the paternal inheritance MMD subgroup and with the normative data. Scores for patients with paternally inherited disease did not differ significantly from normative data for verbal, performance, or full scale intelligence quotients and memory quotients. There were no significant differences in intellectual and cognitive test scores between men and women for the group as a whole, for the maternal inheritance subgroup, or for the paternal inheritance subgroup. It is suggested that inheritance pattern is a necessary variable in studies investigating intellectual and cognitive function in MMD. Although the reason for the association of lower intellectual and cognitive function in MMD of maternal inheritance is not known, the data presented here may be useful for genetic counseling.

Adolescent↗
PubMed1995

Developmental regulation of genomic imprinting during gametogenesis.

Successful mammalian development requires both the male and female genomes. This is due in part to genomic imprinting, which results in offspring inheriting only one functional copy of a gene from either the mother or the father. Evidence suggests that this specialization of the parental genomes is established during gametogenesis when the imprint pattern inherited from the parent is switched to reflect the sex of the progeny. We used reverse transcription-PCR to analyze the allele-specific expression of Igf-2, Igf-2r, and H19 in the testes and ovaries of mice derived from an interspecies cross between Mus musculus and Mus spretus. Because of genomic imprinting, Igf-2 is expressed only from the paternal allele and Igf-2r and H19 only from the maternal allele, in most tissues. Although allele-specific expression was maintained in the neonatal testis and ovary, relaxation of imprinting was detected by 7 days after birth in the male and continued during testis development. In the female, relaxation of the Igf-2 and Igf-2r parental imprints was observed in the adult ovary and oocyte. These results (1) indicate that imprinted expression is relaxed during gametogenesis, presumably as a consequence or prerequisite of the imprinting mechanism, and (2) predict a subsequent imprinting event after which the allele-specific expression of Igf-2, Igf-2r, and H19 reflects the parent of origin.

Alleles↗
PubMed1976

Craniosynostosis, midfacial hypoplasia and foot abnormalities: an autosomal dominant phenotype in a large Amish kindred.

An unusual spectrum of craniofacial and foot abnormalities has been detected within a large midwestern Amish kindred. Enlarged great toes and craniofacial abnormalities suggested Pfeiffer acrocephalosynadactyly type V; however, thumb abnormalities were not present. Eighty-eight affected individuals were observed and another 50 were reliably reported to be affected. An autosomal dominant inheritance pattern was observed associated with variable expressivity. All affected individuals had some clinical or radiologic abnormality of the feet. The phenotypic expression was so variable that the entire spectrum of dominantly inherited craniofacial dysotoses-acrocephalosyndactylys (except the typical Apert syndrome) was seen within this kindred.

Child, Preschool↗
PubMed1995

Periodic catatonia: a schizophrenic subtype with major gene effect and anticipation.

In a family study involving 139 probands with DSM-III-R catatonic schizophrenia and 543 first-degree relatives, we investigated age-specific morbidity risk according to Leonhard's clinical distinction between systematic and periodic catatonia. This dichotomy is based on different types of symptomatology, course, and outcome. In systematic catatonia the age-corrected morbidity risk was 4.6%. In periodic catatonia, however, there was an age-corrected morbidity risk with homogenous psychoses of 26.9%, and more parents than siblings were affected. This points strongly to a major gene effect in periodic catatonia. Furthermore, a pairwise comparison of patients and their parents revealed patterns of anticipation, i.e., the probands' age at the onset of disease was significantly earlier than that of their parents (P < 0.001). Similarly, anticipation was apparent in pedigrees with three successive generations affected. This inheritance pattern with homogenous psychoses and anticipation indicates that genes with trinucleotid repeat expansion or other repetitive elements affecting gene expression may be involved in the etiology of periodic catatonia. Thus, periodic catatonia as a specific clinical subtype of schizophrenia is a promising candidate for molecular genetic evaluation.

Adult↗
PubMed1976

Deafness and vitiligo.

Seven cases of congenital deafness and an autosomal recessive pedigree pattern were observed in an inbred kindred. Three of the cases also had vitiligo, and there were 2 other cases of vitiligo in this kindred. The vitiligo also appeared to have an autosomal recessive inheritance pattern.

Deafness↗
PubMed1992

Dermatopathia pigmentosa reticularis: a report of a family demonstrating autosomal dominant inheritance.

Dermatopathia pigmentosa reticularis is a rare heritable disorder consisting of a triad of cutaneous findings including reticulate hyperpigmentation, noncicatricial alopecia, and onychodystrophy. In addition to this triad, other variable features of dermatopathia pigmentosa reticularis have been described, including adermatoglyphia, hypohidrosis or hyperhidrosis, and palmoplantar hyperkeratosis. Only 10 cases have been described in the world literature to date, and no clear inheritance pattern has been demonstrated. We present a patient with the classic features of the dermatopathia pigmentosa reticularis triad, along with adermatoglyphia, hypohidrosis, and punctate hyperkeratosis of the palms and soles. A family pedigree demonstrates the autosomal dominant inheritance of dermatopathia pigmentosa reticularis.

Adult↗
PubMed1995

Guess LOD approach: sufficient conditions for robustness.

Analysis of genetic linkage between a disease and a marker locus requires specifying a genetic model describing both the inheritance pattern and the gene frequencies of the marker and trait loci. Misspecification of the genetic model is likely for etiologically complex diseases. In previous work we have shown through analytic studies that misspecifying the genetic model for disease inheritance does not lead to excess false-positive evidence for genetic linkage provided the genetic marker alleles of all pedigree members are known, or can be inferred without bias from the data. Here, under various selection or ascertainment schemes we extend these previous results to situations in which the genetic model for the marker locus may be incorrect. We provide sufficient conditions for the asymptotic unbiased estimation of the recombination fraction under the null hypothesis of no linkage, and also conditions for the limiting distribution of the likelihood ratio test for no linkage to be chi-squared. Through simulation studies we document some situations under which asymptotic bias can result when the genetic model is misspecified. Among those situations under which an excess of false-positive evidence for genetic linkage can be generated, the most common is failure to provide accurate estimates of the marker allele frequencies. We show that in most cases false-positive evidence for genetic linkage is unlikely to result solely from the misspecification of the genetic model for disease or trait inheritance.

Genetic Linkage↗
PubMed1977

Spectrum of von Willebrand's Disease: a study of 100 cases. Italian Working Group.

The clinical picture, family history and laboratory findings of 100 patients with von Willebrand's disease (VWD) have been studied in Italy in a multicentre survey from two rural areas with a known high incidence of the disease and from two large cities (Rome and Milan). Bleeding time, procoagulant factor-VIII (VIIIAHF) assay, platelet retention and PRP-ristocetin aggregation were measured in each centre, and plasma samples were frozen and subsequently assayed for factor VIII-related antigen (VIIIAGN) and ristocetin co-factor (VIIIVWF) in one laboratory (Milan). On the basis of the inheritance pattern, clinical severity of the disease and laboratory findings, patients with VWD were separated into two groups. In 17 patients the absence of a family history of bleeding, a high incidence of parental consanguinity and involvement of both sexes suggested an autosomal recessive mode of inheritance; the unusual severity of the disease with markedly abnormal results of all six laboratory measurements (and frequent reduced levels of VIIIAGN and VIIIVWF in the unaffected parents) were consistent with the homozygous state. In 83 patients, the disease was familial (being transmitted as an autosomal dominant trait) and of moderate clinical severity. In these, VIIIVWF was usually much lower than VIIIAHF and VIIIAGN. The findings suggest that although some patients may present with simultaneous abnormalities of all six studied laboratory measurements, the majority show a variation in the spectrum of the abnormal results, without any obvious simple pattern.

Antigens↗
PubMed2025

Bistable Mutation-Selection Equilibria and Violations of Fisher's Theorem in Tetraploids: Insights from Nonlinear Dynamics.

Polyploidy and whole genome duplication (WGD) are widespread biological phenomena with substantial cellular, meiotic, and genetic effects. Despite their prevalence and significance across the tree of life, population genetics theory for polyploids is not well developed. The lack of theoretical models limits our understanding of polyploid evolution and restricts our ability to harness polyploidy for crop improvement amidst increasing environmental stress. To address this gap, we developed and analyzed deterministic models of mutation-selection balance for tetraploids under polysomic (autotetraploid) and disomic (allotetraploid) inheritance patterns and arbitrary dominance relationships. We also introduced a new mathematical framework based on ordinary differential equations and nonlinear dynamics for analyzing the models. We find that autotetraploids approach Hardy-Weinberg Equilibrium 33% faster than allotetraploids, but the different tetraploid inheritance models show little differences in mutation load and allele frequency at mutation-selection balance. Our model also reveals two bistable points of mutation-selection balance for dominant alleles with biased mutation rates over a wide range of selection coefficients in the tetraploid models compared to bistability in only a narrow range for diploids. Finally, using discrete time simulations, we explore the temporal dynamics of allele frequency and fitness change and compare these dynamics to the predictions of Fisher's Fundamental Theorem of Natural Selection. While Fisher's predictions generally hold, we show that the bistable dynamics for dominant mutations fundamentally alter the associated temporal dynamics. Overall, this work develops foundational theoretical models that will facilitate the development of population genetic models and methodologies to study evolution in empirical tetraploid populations.

Fisher&#x2019;s Fundamental Theorem↗
PubMed1992

Mitochondrial DNA and genetic disease.

Since the human mitochondrial genome was characterised and sequenced in 1981, it has been viewed as the likely site of genetic diseases showing a maternal inheritance pattern and associated with defects of the respiratory chain, such as the mitochondrial myopathies (MMs). The properties that make it a candidate for the source of such conditions are that it encodes polypeptides involved in electron transport and that it is maternally inherited. However, several of the mtDNA diseases only fulfill one or other of these criteria: the first group of mtDNA diseases showed only sporadic deletions, and the first point mutation in Leber's Hereditary Optic Neuropathy (LHON) is not associated with a clear biochemical defect. Furthermore, it is now clear that both autosomal dominant and probably recessive nuclear genes can cause abnormalities of mtDNA. Each of these major groups will be considered in turn.

Adult↗
PubMed1995

Intermediate inheritance of Tourette syndrome, assuming assortative mating.

Segregation analysis incorporating assortative mating was used to test for major locus inheritance of Tourette syndrome in a single large pedigree containing 182 members. The analysis provided evidence of a major locus with an intermediate inheritance pattern for which the penetrance was estimated from the data as 28% in heterozygotes and 98%-99% in homozygotes. A significant assortative mating correlation was estimated from the data as 70%-79%. In contrast, when assortative mating was not included in the model, intermediate inheritance was not inferred. If, in addition, constancy of the allele frequencies across generations was not assumed, Mendelian transmission was rejected. Each subject, affected or unaffected, was assigned a score reflecting the presence and severity of symptoms. Higher means scores in affected homozygotes than in affected heterozygotes suggested greater severity in homozygotes: genotype information was obtained from genotype probabilities computed assuming intermediate inheritance.

Adolescent↗
PubMedDate not supplied

Influence of parental genotype on plastid inheritance in Medicago sativa.

Research using chlorophyll-deficient mutants has shown that plastids are inherited biparentally in Medicago sativa L. (alfalfa). Variation in plastid transmission behavior was observed among crosses in earlier studies, but it was not determined whether this variation was under genetic control. In my research, genetic analyses of the frequencies of normal (G), chlorophyll-deficient (CD), and sectored (G and CD) progenies produced from G x CD crosses demonstrated that plastid inheritance patterns in alfalfa are influenced by both maternal and paternal genotypes. A strong paternal bias in plastid transmission existed in the majority of crosses despite the potential developmental disadvantages associated with paternally contributed CD plastids. The high frequencies of uniparental progenies suggest that genetic control of plastid inheritance in alfalfa may be exerted through effects on the number and distribution of maternal and paternal plastids early in embryo development.

Chlorophyll↗
PubMed1992

von Willebrand disease family studies: comparison of three methods of analysis of the von Willebrand factor gene polymorphism related to a variable number tandem repeat sequence in intron 40.

A region with a variable number of tandem ATCT repeats (VNTR) has previously been localized within intron 40 of the von Willebrand factor (vWF) gene. In the present report we describe the use of this polymorphism as a genetic marker to study the inheritance pattern in five families affected with various types of von Willebrand disease (vWD): types I, IIA, IIB, IIC and the newly characterized variant with totally defective FVIII binding. Three means of investigation previously reported, all using polymerase chain reaction (PCR) amplification of this vWF gene region, were compared in terms of informativeness. The two direct single-step procedures analysing only partial sequences of the VNTR region turned out to be less informative (three studies informative out of five) than the third method characterizing the variability of the whole VNTR sequence. This latter approach, based on the analysis of the Alu I restriction pattern of the VNTR region, was informative in all the families investigated, therefore avoiding the need to combine it with other genetic marker studies for efficient gene tracking. In conclusion, this two-step (PCR and digestion) method is the most informative for the characterization of the inheritance of the different subtypes of vWD and for the prenatal diagnosis of its severe forms.

Alleles↗
PubMed1984

Segregation patterns of polymorphic restriction sites of the gene encoding the alpha subunit of human chorionic gonadotropin in trophoblastic disease.

The gene encoding the alpha subunit of human chorionic gonadotropin contains at least two polymorphic sites in its 3' flanking region detected by restriction enzymes HindIII and EcoRI. We used these polymorphic sites as markers of tissue genotype in normal placenta, hydatidiform mole, choriocarcinoma, and peripheral leukocytes. As expected, inheritance patterns of most hydatidiform moles showed only a paternal genetic contribution. However, one uncommon DNA polymorphism pattern, homozygosity for the absence of the EcoRI site and the presence of the HindIII site, predominated in choriocarcinoma. Thus, our results suggest that moles which have this uncommon polymorphism pattern appear particularly likely to develop into choriocarcinoma.

Choriocarcinoma↗
PubMed1988

Acrodysostosis: report of a 13-year-old boy with review of literature and metacarpophalangeal pattern profile analysis.

We report on a 13-yr-old boy with acrodysostosis, a review of 30 cases in the literature, and metacarpophalangeal pattern profile (MCPP) analysis. The prominent manifestations (present in greater than 75% of cases) of this condition include nasal and maxillary hypoplasia, peripheral dysostosis, first ray hyperplasia of the foot, acromesomelic brachymelia, decreased interpedicular distance, advanced skeletal maturation and mental retardation. Results of chromosome studies have been normal. An autosomal dominant inheritance pattern was reported in two families. Maternal and paternal ages were 2 and 3 yr, respectively, above the average age of the general parent population, which suggests that advanced parental age may be a factor in the cause of this condition. A characteristically abnormal MCPP was found in our patient and in 16 additional cases studied from the literature. A mean MCPP was developed for the syndrome. MCPP analysis may be useful as a diagnostic tool in patients suspected to have acrodysostosis.

Adolescent↗
PubMed2026

Exome sequencing and large-scale analysis of electronic medical record-linked biobank data identify candidate deafness genes.

INTRODUCTION: Rapid advances in whole-exome sequencing (WES) have enabled large-scale detection of pathogenic variants. Although hundreds of genes are implicated in hearing loss, up to half of inherited cases remain unsolved, limiting eligibility for gene therapy trials that require genetic diagnosis. Biobanks and electronic medical records (EMRs) offer opportunities to integrate genomic and clinical data at scale and expand the spectrum of hearing loss genes. Despite clinical value, EMRs often lack key information such as inheritance patterns, posing challenges for accurate interpretation. METHODS: WES was performed on DNA samples from 1038 hearing-impaired patients enrolled in the Maccabi Research and Innovation Center Tipa Biobank. Clinical data were extracted from EMRs. Audiograms were available for all cases, although data on age of onset, family history and mode of inheritance were mostly unavailable. We applied a scalable bioinformatics analysis strategy for high-throughput annotation, filtering and prioritisation of WES variants across more than 1000 patients, designed to accommodate incomplete and heterogeneous clinical records. RESULTS: Using this approach, 15% of cases were solved or potentially solved through known or novel variants in established deafness genes. Homozygous variants in novel candidate genes were identified in 3% of cases. Functional characterisation was performed for promising candidate genes to validate their role in the ear. CONCLUSION: These findings demonstrate that WES can determine disease aetiology in large, genetically heterogeneous populations, even in the context of incomplete clinical data. This approach supports large-scale genetic screening and provides a framework for identifying patients who may benefit from emerging gene-based therapies.

Genetic Testing↗
PubMed1994

Genetics of the Costello syndrome.

Although Costello syndrome is considered to be an autosomal recessive disorder, review of 20 families demonstrated that the 37 sibs of the probands were all normal. In 6 families on whom pedigrees were not available, 2 affected sib-pairs were born. Even if there were no normal offspring in these latter families, the occurrence of the Costello syndrome in only 2 of 39 sibs virtually excludes an autosomal recessive inheritance pattern (P = 0.999). Moreover, a significant increase of mean paternal age (38.0 yr) and paternal-maternal age difference (7.36 yr) suggests sporadic autosomal dominant mutations as a likely cause. The 2 reported cases of affected sibs born to healthy parents may be explained by gonadal mosaicism, although heterogeneity with a small proportion of recessively inherited cases cannot be excluded.

Abnormalities, Multiple↗