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At least 577 records · Page 32Linked to original sources
PubMed1996

Renal expression of a transforming growth factor-alpha transgene accelerates the progression of inherited, slowly progressive polycystic kidney disease in the mouse.

Polycystic kidney disease (PKD) is a prevalent inherited disease in human beings. The pathogenesis of PKD is as yet unclear. The epidermal growth factor family of proteins has been implicated in PKD based largely on in vitro data. To determine whether these growth factors contribute to the progression of inherited PKD in vivo, we crossed mice with a transgene for human transforming growth factor-alpha (TGF-alpha, a member of the epidermal growth factor (EGF) family) and mice with the pcy gene (which causes a slowly progressive form of PKD very similar to human autosomal dominant PKD). Renal expression of the TGF-alpha transgene in cystic mice (homozygous for the pcy gene) accelerated the development of PKD as shown by an increased kidney weight as a percent of body weight and an increased volume density of renal cysts at 8.5 weeks of age. However, renal expression of the TGF-alpha transgene did not appear to precociously initiate cyst development (at 6.5 weeks), nor did it cause an increase in the final degree of renal enlargement (at 29 weeks). Thus TGF-alpha accelerated the enlargement of cysts once initiated. At 8.5 weeks of age, renal expression of the TGF-alpha mRNA correlated positively with the amount of renal enlargement. At all time points studied, cystic kidneys exhibited increased expression of c-myc mRNA as compared with phenotypic normal kidneys, consistent with PKD being a hyperplastic disease of renal tubules. However, the renal expression of c-myc in 8.5 week cystic kidneys, with or without the transgene, did not correlate with the degree of renal enlargement. The results of this study suggest that EGF-like proteins may accelerate the progression of inherited renal cystic disease. However, the final degree of cystic change is dictated by the primary disease process rather than by the continued presence of growth factor.

Aging↗
PubMed2003

Pseudo-autosomal dominant inheritance of PARK2: two families with parkin gene mutations.

We report two families (Family S and Family N) with early-onset parkinsonism in two generations. The mode of inheritance appeared to be autosomal dominant, however, haplotye analysis suggested linkage to chromosome 6q25.2-27, the PARK2 locus, and all affected members were homozygotes in their haplotypes. In Family S, the affected father was married to unaffected mother, who carried one disease-linked haplotype at chromosome 6q25.2-27. In Family N, the unaffected mother carried one disease-linked haplotype. Quantitative PCR amplification analysis revealed exon 3 deletion in Family S and exon 5 deletion in Family N. The age of onset was from 18 to 22 years in Family S and 25 to 42 years in Family N. In both of their hometowns, most people lived in the same districts for many generations and consanguineous marriages had been common. Thus, the carrier state of the parkin gene might have been high in those communities, and marriage of a patient and a carrier is expected to result in autosomal dominant like inheritance. We conclude that PARK2 cannot be excluded even if the mode of inheritance appears as autosomal dominant, when the affected patients are young.

Aged↗
PubMed2000

Inheritance of pancreatic cancer in pancreatic cancer-prone families.

Families are being increasingly recognized as carrying an inherited susceptibility for pancreatic cancer, apparently unrelated to any currently recognized syndrome. The authors provide a review of the current evidence for familial susceptibility to pancreatic cancer. A formal segregation analysis of the pattern of inheritance of pancreatic cancer in 70 families from the National Registry for Familial Pancreatic Cancer is described. This analysis suggests a single major gene with an autosomal dominant mode of inheritance controlling susceptibility for pancreatic cancer in these families.

Adenocarcinoma↗
PubMed1992

Nontraditional inheritance.

It has become clear in recent years that not all forms of inheritance follow classical mendelian laws regarding the equal contribution from both parents. These nontraditional modes of inheritance and gene expression include cytoplasmic inheritance, mosaicism, uniparental disomy, and genomic imprinting. All of these have been implicated in human genetic disorders and cancers and thus need to be kept in mind when trying to understand unusual observations in the clinic as well as when providing genetic counseling.

Chromosome Aberrations↗
PubMed1996

Inherited breast cancer.

Five to ten percent of breast cancer is attributable to the autosomal dominant inheritance of a high-risk susceptibility gene. There are a number of known inherited cancer syndromes that confer a higher risk of breast cancer. Recently, the BRCA1 gene, which is responsible for 45% of hereditary early-onset breast cancer and for the majority of co-inheritance of breast and ovarian cancer, has been cloned. Another gene that confers an increased risk of breast cancer is the BRCA2 gene, which maps to the long arm of chromosome 13 by linkage analysis. Mutations in BRCA2 account for approximately 40% of hereditary early-onset breast cancer. In addition, at least 7% of breast cancer may occur in women who are heterozygous for mutations in a gene for ataxia-telangiectasia, an autosomal recessive chromosome instability syndrome. Predictive testing for some predisposing conditions is possible through indirect or direct mutation testing. In this article, the genetics of breast cancer are reviewed, and practical concerns for the surgeon in counseling high-risk patients are addressed.

Ataxia Telangiectasia↗
PubMed1987

Inherited abnormalities of the platelet membrane and secretory granules.

Platelet stimulus-activation-contraction-secretion coupling is linked to fundamental modifications in the biochemistry and ultrastructure of the platelet surface and the membranes enclosing storage organelles. It is not surprising, therefore, that membrane defects are common in platelets from patients with inherited hemorrhagic disorders caused by platelet dysfunction. In fact, it might be stated that all inherited disorders of platelet function are related directly or indirectly to abnormalities of membranes. The current review discusses the state of knowledge on inherited platelet membrane defects of the cell surface and storage organelles.

Bernard-Soulier Syndrome↗
PubMed1998

Inherited carcinomas of the kidney.

Studies of families with inherited carcinomas have provided powerful tools to identify the genes involved in the pathogenesis of human cancers. In this review, we summarize the clinical, pathological, and genetic characteristics of the inherited carcinomas of the kidney. We emphasize the observation that different genes predispose to histologically different types of renal carcinoma. Hereditary papillary renal carcinoma, a recently described inherited disorder, is discussed in detail along with the predisposing gene, the MET protooncogene. The data support a classification of renal carcinomas based on molecular genetics.

Adenocarcinoma, Clear Cell↗
PubMed2002

Non-Mendelian inheritance and homology-dependent effects in ciliates.

Ciliates are single-celled eukaryotes that harbor two kinds of nuclei. The germline micronuclei function only to perpetuate the genome during sexual reproduction; the macronuclei are polyploid, somatic nuclei that differentiate from the micronuclear lineage at each sexual generation. Macronuclear development involves extensive and reproducible rearrangements of the genome, including chromosome fragmentation and precise excision of numerous internal sequence elements. In Paramecium and Tetrahymena, homology-dependent maternal effects have been evidenced by transformation of the vegetative macronucleus with germline sequences containing internal eliminated sequences (short single-copy elements), which can result in a specific inhibition of the excision of the homologous elements during development of a new macronucleus in the sexual progeny of transformed clones. Furthermore, transformation of the Paramecium maternal macronucleus with cloned macronuclear sequences can specifically induce new fragmentation patterns or internal deletions in the zygotic macronucleus. These experiments show that the processing of many germline sequences in the developing macronucleus is sensitive to the presence and copy number of homologous sequences in the maternal macronucleus. The generality and sequence specificity of this transnuclear, epigenetic regulation of rearrangements suggest that it is mediated by pairing interactions between zygotic sequences and sequences originating from the maternal macronucleus, presumably RNA molecules. Alternative macronuclear versions of the genome can be maternally inherited across sexual generations, suggesting a molecular model for some of the long-known cases of non-Mendelian inheritance, and in particular for the developmental determination and maternal inheritance of mating types in Paramecium tetraurelia.

Animals↗
PubMed1998

Frequency of inherited bleeding disorders in women with menorrhagia.

BACKGROUND: Although menorrhagia is a common gynaecological symptom, a specific cause is identified in less than 50% of affected women. We investigated the frequency of inherited bleeding disorders in women with menorrhagia. METHODS: Women referred for investigation of menorrhagia whose pelvis was normal on clinical examination and who had an estimated menstrual blood loss of more than 80 mL were studied. A detailed menstrual history and history about other bleeding symptoms was taken. The activated partial thromboplastin time, factor VIII activity, von-Willebrand-factor antigen and activity, and factor XI (FXI) were measured in all patients; further tests were done when results were at or outside the limits of the assays. FINDINGS: 150 women were screened. An inherited bleeding disorder was diagnosed in 26 (17%) patients: the disorders were von Willebrand's disease of mild (15) or moderate severity (three), mild FXI deficiency (four), mild von Willebrand's disease and FXI deficiency (one), combined von Willebrand's disease, FXI deficiency, and factor X deficiency (one), carriage of haemophilia-A gene (one), and platelet dysfunction (one). The frequency of von Willebrand's disease and FXI deficiency were 13% (95% CI 7.9-18.8%) and 4% (1.5-8.5%), respectively. Menorrhagia since menarche was noted in 11 (8.9%) of 123 women without a bleeding disorder compared with 13 (65%) of 20 women with von Willebrand's disease (p=0.001) and four (66.7%) of six women with FXI deficiency (p<0.001). INTERPRETATION: Inherited bleeding disorders are found in a substantial proportion of women with menorrhagia and a normal pelvis examination. We suggest that such patients should be investigated for these disorders-especially von Willebrand's disease-before invasive procedures are done.

Adult↗
PubMed1993

Autosomal dominant inheritance of iridogoniodysgenesis and cataract.

BACKGROUND: There has been only one report in the literature of iridogoniodysgenesis associated with cataracts in two brothers. In that report, the authors conclude that the condition was inherited by autosomal recessive transmission. METHODS: The authors evaluated 10 members in three generations of a family in which there is a striking prevalence of pre-senile hypermature cataract formation and iridogoniodysgenesis. In addition, historical information regarding two deceased members of the family was studied. RESULTS: Six of 10 family members evaluated have iridogoniodysgenesis. Four of five siblings have had pre-senile hypermature cataracts. Despite the iridogoniodysgenesis, there appears to be no association with glaucoma in any of these patients. CONCLUSION: The inheritance pattern of this syndrome appears to be that of autosomal dominance with variable penetrance. The authors believe that this report helps to clarify the inheritance pattern of this previously described hereditary syndrome.

Adolescent↗
PubMed1999

Pigmentary retinal dystrophy and the syndrome of maternally inherited diabetes and deafness caused by the mitochondrial DNA 3243 tRNA(Leu) A to G mutation.

OBJECTIVE: To study the association of retinal disease and the syndrome of maternally inherited diabetes and deafness caused by an A to G mutation in the tRNA leucine gene at base pair 3243 (A3243G) of the mitochondrial genome. DESIGN: Observational study of a genetically defined subject group. PARTICIPANTS: Thirteen subjects with the mitochondrial DNA A3243G mutation from seven different pedigrees with maternally inherited diabetes and deafness. INTERVENTION: Assessment of visual symptoms and visual acuity, dilated indirect ophthalmoscopy, retinal photography, and retinal electrophysiology. MAIN OUTCOME MEASURES: Loss of vision, funduscopic evidence of pigmentary retinal disease or diabetic retinopathy, and electrophysiologic evidence of defective functioning of the retinal pigment epithelium/photoreceptor complex. RESULTS: Funduscopic examination revealed abnormalities of retinal pigmentation in ten subjects (77%). Defects included speckled and patchy hyperpigmentation at the posterior pole of the fundus, particularly in the macular area, and varying degrees of loss of retinal pigmentation. Three subjects (23%) had visual symptoms, which included night blindness, visual loss, and photophobia. Electrophysiologic studies revealed impaired electro-oculogram responses in four of nine subjects with defects of retinal pigmentation (44%), two of whom also had much reduced scotopic and, to a lesser extent, flicker electroretinogram b wave potentials. Two subjects had diabetic retinopathy, including one with retinal depigmentation and impaired electro-oculogram activity. Both subjects with diabetic retinopathy had unilateral reduced electroretinogram responses, especially oscillatory potentials. CONCLUSIONS: Abnormalities of retinal pigmentation are common in subjects with maternally inherited diabetes and deafness caused by the mitochondrial DNA A3243G mutation. Visual symptoms, in particular loss of visual acuity, appear to be infrequent. The combination of deficits in the electro-oculogram and scotopic and flicker electroretinograms suggests that the retinal dystrophy includes defective functioning of retinal pigment epithelial cells and of both rod and cone photoreceptors. The pigmentary retinopathy does not prevent diabetic retinopathy; a single subject had funduscopic and electrophysiologic evidence of both diseases. Current evidence suggests that the mitochondrial DNA A3243G mutation accounts for 0.5% to 2.8% of diabetes. Most ophthalmic and diabetic clinics are therefore likely to contain such patients, who may benefit from identification of the genetic defect causing their disease and from genetic counseling.

Adenine↗
PubMed1998

Inheritance of the mammalian Golgi apparatus during the cell cycle.

The creation and propagation of the intricate Golgi architecture during the cell cycle poses a fascinating problem for biologists. Similar to the inheritance process for nuclear DNA, the inheritance of the Golgi apparatus consists of biogenesis (replication) and partitioning (mitosis/meiosis) phases, in which Golgi components must double in unit mass, then be appropriately divided between nascent daughter cells during cytokinesis. In this article we focus discussion on the recent advances in the area of Golgi inheritance, first outlining our current understanding of the behaviour of the Golgi apparatus during cell division, then concluding with a more conceptual discussion of the Golgi biogenesis problem. Throughout, we attempt to integrate ultrastructural and biochemical findings with more recent information obtained using live cell microscopy and morphological techniques.

Animals↗
PubMed1984

The inheritance of common baldness: two B or not two B?

So far, it is a widely accepted opinion that androgenetic alopecia is caused by an autosomal dominant gene with reduced penetrance in women. This view is essentially based on a family study performed by Osborn in 1916. She believed that balding men would be either heterozygous (Bb) or homozygous (BB), whereas balding women would be homozygous (BB). By contrast, we here present five arguments favoring a polygenic inheritance of the trait: (1) the high prevalence of the trait, (2) the distribution of balding patterns in the general population along a gaussian curve of variation, (3) the fact that the risk increases with the number of relatives already affected, (4) the slightly increased risk of relatives of severely affected women as compared to the relatives of mildly affected women, and (5) the fact that a predisposition inherited from an affected mother is of greater importance than that inherited from an affected father. In conclusion, the simple mendelian model of Bb and BB can no longer be upheld.

Adult↗
PubMed2002

Molecular diagnosis of inherited neuromuscular disease.

Prevention of inherited disease in companion animals is largely dependent on prebreeding identification of carriers of autosomal recessive disease traits. Molecular diagnosis is emerging as a convenient and reliable method of carrier detection, but few molecular diagnostic tests of inherited neuromuscular disease are readily available. New test development depends on investigations to determine disease genes and the disease causing mutations. A general approach to molecular diagnosis of inherited disorders is discussed.

Animals↗
PubMed2003

Celiac disease in patients with sporadic and inherited cardiomyopathies and in their relatives.

AIMS: To investigate celiac disease (CD) and related co-morbidity in patients with familial and sporadic cardiomyopathy and in their relatives. METHODS AND RESULTS: We screened anti-human-tissue-transglutaminase (IgA and IgG anti-h-tTG) and anti-endomysial antibodies (AEAs) in 238 consecutive adult patients with inherited or sporadic dilated cardiomyopathy (DCM), 418 relatives, and 2000 healthy blood donors. HLADQ2-DQ8 was tested in tTG-positive subjects. The IgA-tTG-positive patients with cardiomyopathy underwent duodenal biopsy. Twenty-six subjects were tTG-positive: five DCM patients (2.1%), two of 28 (7.1%) and three of 390 (0.7%) relatives with and without echocardiographic abnormalities respectively, and 16 controls (0.8%). Twenty-two of 26 subjects were AEA-positive, and 25 HLA-positive. Of the five patients with cardiomyopathy and biopsy-proven CD, four suffered iron-deficiency anaemia. Two CD-positive DCM patients and two tTG-positive relatives were from families with inherited disease in which CD did not co-segregate with DCM. CONCLUSIONS; The higher prevalence of CD in patients with sporadic or inherited DCM, and of tTG-positive serology in relatives with echocardiographic abnormalities, suggests that immune-mediated mechanisms are active in subsets of patients/families. However, gluten intolerance cannot be considered causative since CD seems to be associated but not co-segregated with DCM in familial cases.

Adolescent↗
PubMed1995

The rarer inherited coagulation disorders: a review.

Of the inherited bleeding disorders, haemophilia A, haemophilia B and von Willebrand's disease make up together well over 80% of those registered with the UK Haemophilia Centre Directors. The common simple screening tests of coagulation may overlook some of the more rare disorders and it is clearly important that such uncommon bleeding disorders are excluded during the course of the investigation of children considered to be suffering from non-accidental injury. In this article, some of the rare inherited bleeding disorders are considered, including haemophilia B Leyden, deficiencies of factors VII, X, XI, and XII, as well as inherited defects of platelet number and function. Presenting features are described and recommendations regarding appropriate therapy given. In order to assist in advancing understanding of the biochemistry and molecular genetics of these disorders, clinicians are encouraged to share clinical information and, where appropriate, blood samples with interested research workers.

Blood Coagulation Disorders↗
PubMed1994

Inherited diseases of the glomerular basement membrane.

The inherited diseases of the glomerular basement membrane include Alport's syndrome (AS), nail-patella syndrome, and thin basement membrane nephropathy. Classical AS is inherited in an X-linked manner and accounts for approximately 85% of the cases. Its manifestations include hematuria, sensorineural hearing loss, ocular defects, and a progression to renal failure. A defect(s) in the alpha 5 (IV) chain of type IV collagen is believed to be the etiology of classic AS, and alterations in its encoding gene localized to the X-chromosome have been elucidated. Although isolated cases of anti-glomerular basement membrane glomerulonephritis have been reported following renal transplantation in patients with AS, it is considered an effective form of renal replacement therapy. Less is known regarding the genetic basis of the autosomal-dominant form of AS, which apparently accounts for the remaining 15% of the cases. Nail-patella syndrome is characterized by nail dysplasia, patellar hypoplasia or aplasia, and nephropathy. It is inherited in an autosomal-dominant fashion with the gene locus assigned to the long arm of chromosome 9. Possible linkage between the COL5A1 gene and the gene for nail-patella syndrome has been suggested. Approximately 30% of the patients progress to end-stage renal failure. Renal transplantation has been successful in treating patients who progress to end-stage renal failure. Thin basement membrane nephropathy is an autosomal dominant trait that accounts for approximately 30% of the cases presenting as persistent, asymptomatic hematuria. The cause of thin basement membrane nephropathy is unknown at present. No decline in renal function is associated with thin basement membrane nephropathy.

Adolescent↗
PubMed1996

Inheritance of randomness.

The mouse mutant iv is characterized by "a random determination of a developmental process' in that 50 rather than 100% of the homozygotes have situs inversus. The same explanation is given to the inheritance of situs inversus in the human immotile-cilia syndrome. There are probably two alleles of the responsible gene, one for control of the proper asymmetry and one without control and hence resulting in equal numbers of situs solitus and situs inversus in the homozygote. Left-handedness may be similarly inherited; furthermore, because of its high prevalence (around 10-12%) it has been assumed that there is an advantage of carrying both alleles ("balanced polymorphism'). With these two assumptions, a prevalence of left-handedness of 12.5% is expected, a 50% chance of left-handedness in matings between two left-handed persons, and equal numbers of discordant and left-handed concordant monozygotic twins. These values are close to those actually found. As the values for (female) homosexuality are similar to those of left-handedness a similar inheritance is proposed.

Adult↗