Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Heterozygote”

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 199 records · Page 11Linked to original sources
PubMed1973

Homocystinuria: heterozygote detection using phytohemagglutinin-stimulated lymphocytes.

Deficiency of cystathionine synthase activity results in the clinical syndrome of homocystinuria. Using phytohemagglutinin (PHA)-stimulated lymphocytes as a readily available source of this enzyme, its activity has been compared in 48 control subjects, seven homozygotes affected with homocystinuria, and 17 obligate heterozygotes. PHA-induced enzyme levels were highest in controls (mean +/-SEM, 666.9+/-70.2 pmol cystathionine formed/mg protein per 4 h), intermediate in heterozygotes (114.4+/-27.3), and absent to severely deficient in homozygotes (2.0+/-1.6). Since only three of the 17 values from the obligate heterozygotes overlapped into the control range, this simple method may become clinically useful for heterozygote detection of carriers of the gene for abnormal cystathionine synthase. In addition, this system for induction of cystathionine synthase in lymphocytes has a more general relevance to human biochemical genetics in that it demonstrates that the absence of an enzyme in a normal cell does not preclude using that source for diagnosis of genetic disease if the enzyme can be induced.

Adolescent↗
PubMed1994

Prenatal counseling in heterozygotes for ornithine transcarbamylase deficiency.

X-linked ornithine transcarbamylase deficiency (OTCD) often leads to fatal neonatal hyperammonemia in affected males (hemizygotes). In prenatal management of subsequent pregnancies, families carrying female fetuses are often reassured of the low risk of clinically overt disease. We suggest that such reassurance may be misleading. While OTCD heterozygotes may show no symptoms or only mild protein intolerance, the clinical course in a fraction of children can include manifestations similar to those in affected males. We present three cases of symptomatic and previously undiagnosed OTCD heterozygotes to illustrate the potential severity of this condition. Significant improvement in function and growth followed diagnosis and treatment; however, two of the three children remain significantly developmentally delayed. While a quantitative risk estimate cannot be derived from these data, the cases are indicative of an adverse outcome in manifesting heterozygotes. Accordingly, OTCD carrier families should be counseled regarding the possibility of significant hyperammonemia, neurologic deficit, and the need for pharmacologic and dietary intervention in their heterozygote daughters.

Adolescent↗
PubMed2003

Response of obligate heterozygotes for phytosterolemia to a low-fat diet and to a plant sterol ester dietary challenge.

Twelve obligate heterozygotes from two kindreds were ascertained through phytosterolemic probands homozygous for molecular defects in the ATP binding cassette (ABC) half transporter, ABCG8. The response of these heterozygotes to a Step 1 diet low in fat, saturated fat, and cholesterol, and to 2.2 g daily of plant sterols (as esters) was determined in Protocol I (16 weeks) and Protocol II (28 weeks) during three consecutive feeding periods: Step 1/placebo spread; Step 1/plant sterol spread; and Step 1/placebo spread (washout). At baseline, half the heterozygotes had moderate dyslipidemia and one-third had mildly elevated campesterol and sitosterol levels. On the Step 1/placebo spread, mean LDL cholesterol decreased significantly, 11.2% in Protocol I (n = 12), and 16.0% in Protocol II (n = 7). Substitution with plant sterol spread produced a significant treatment effect on LDL levels in Protocols I and II. Conversely, the mean levels of campesterol and sitosterol increased 119% and 54%, respectively, during the use of plant sterol spread for 6 weeks in Protocol I, an effect mirrored for 12 weeks in Protocol II. During the placebo spread washouts, LDL levels increased, while those of plant sterols decreased to baseline levels in both protocols. In conclusion, phytosterolemic heterozygotes respond well to a Step 1 diet, and their response to a plant sterol ester challenge appears similar to that observed in normals.

Adolescent↗
PubMed1976

Hurler syndrome: alpha-L-iduronidase activity in leukocytes as a method for heterozygote detection.

Alpha-L-Iduronidase activity and beta-galactosidase activity were determined in mixed leukocyte preparations in 10 families in which the Hurler syndrome had occurred. Affected patients, heterozygotes, and normal subjects were clearly distinguished by alpha-L-iduronidase activity alone. Patients had 0-3%, obligate heterozygotes 19-60%, and normal subjects 83-121% of the mean normal activity. There was no overlap between heterozygotes and normal subjects. Although the mean alpha-L-iduronidase to beta-galactosidase ratio was significantly lowered in heterozygotes when compared with that of normal subjects, appreciable overlap was noted between the two groups.

Adolescent↗
PubMed1983

Various sulfatase activities in leukocytes and cultured skin fibroblasts from heterozygotes for the multiple sulfatase deficiency (mukosulfatidosis).

In heterozygotes for multiple sulfatase deficiency (MSD), several sulfatase activities including arylsulfatases A, B1, B2, and C, and cholesterol sulfatase were 40-50% of normals in cultured skin fibroblasts and 70-80% of normals in leukocytes. In MSD patients, these enzyme activities were deficient or reduced. DEAE-Sepharose column chromatographic patterns of 4-methylumbelliferyl sulfatases A, B1, and B2 in leukocytes and cultured skin fibroblasts from MSD patients and heterozygotes were also consistent with the above data. These data indicate that several sulfatase activities in heterozygotes of MSD exhibited intermediate activities as observed in the heterozygote state of other autosomal recessive inherited diseases.

Arylsulfatases↗
PubMed1986

Very long-chain fatty acids in erythrocyte membrane sphingomyelin: detection of ALD hemizygotes and heterozygotes.

We used mass fragmentography to analyze a very long-chain fatty acid composition of erythrocyte membrane sphingomyelin. The content of hexacosanoic acid (C26:0), tetracosanoic acid (C24:0) and docosanoic acid (C22:0) in adrenoleukodystrophy (ALD) hemizygotes and heterozygotes was significantly higher than in controls. Although the ratio of C26:0 to C22:0 in 18 of the 46 controls was in the range of ALD heterozygotes, the absolute content of C26:0 and C24:0 in controls did not overlap with ALD hemizygotes or heterozygotes. The content of C26:0 and C24:0 is more reliable for detection of ALD hemizygotes and heterozygotes than the ratio of C26:0 to C22:0 when red cell sphingomyelin is used for diagnosis.

Adolescent↗
PubMed2001

Severe hypercholesterolemia in a double heterozygote for lipoprotein lipase deficiency (LPL(Arita)) and apolipoprotein epsilon4: a report of a family with LPL(Arita).

Although heterozygous lipoprotein lipase (LPL) deficiency is not rare, only part of the phenotypes may have been reported in Japan. Here we describe a Japanese family with LPL(Arita), the most common mutation linked to familial LPL deficiency in Japan, and show for the first time a heterozygote for the mutation who had marked hypercholesterolemia due to increased low-density lipoprotein (LDL) cholesterol. The proband's mother, one of the heterozygotes for LPL(Arita) in the family, had both severe hypercholesterolemia (total cholesterol 306 mg/dl) with an especially increase in LDL-cholesterol and mild hypertriglyceridemia (180 mg/dl). She had normal LDL receptor activity and did not show clear evidence of possible causes of secondary hyperlipidemia. In addition to being heterozygous for LPL deficiency, she was also heterozygous for apo epsilon4. Because the epsilon4 allele is known to be associated with higher LDL-cholesterol, heterozygous apo epsilon4 may be one of causes of her LDL-cholesterol elevation. The other three heterozygotes for LPL(Arita) were moderate drinkers, and all of them had both remarkable hypertriglyceridemia and mild hypercholesterolemia due to increased very-low-density lipoproteins (VLDL). The results suggest that heterozygotes for LPL(Arita) can exhibit various phenotypes of hyperlipidemia, that is, hypertrigliceridemia and/or hypercholesterolemia due to not only increased VLDL but also increased LDL. The phenotypes appear to depend on some other genetic and environmental factors.

Adult↗
PubMed1979

Arginase and free amino acids in hyperargininemia: leukocyte arginine as a diagnostic parameter for heterozygotes.

Arginase activity and free amino acids were measured in plasma, erythrocytes and leukocytes of patients with hyperargininemia and in controls. There is no arginase activity in the leukocytes and erythrocytes of homozygous patients; in heterozygotes it is normal to low. The activity is 50 to 100 times higher in leukocytes than in erythrocytes. In controls as well as in patients and heterozygotes, the amino acid concentrations are higher in leukocytes than in plasma and erythrocytes. In addition to the increased arginine in the three blood compartments (the result of an arginase deficiency), there is also an obvious decrease of aspartic acid in the erythrocytes of the patients. The arginine concentration in leukocytes of heterozygotes is as high as in homozygotes and can therefore be used as a diagnostic parameter for heterozygotes.

Amino Acid Metabolism, Inborn Errors↗
PubMed1984

Alternate organization of alpha G-Philadelphia globin genes among U.S. black and Italian Caucasian heterozygotes.

Seven Hb G-Philadelphia (Hb G) heterozygotes from three Caucasian families from Northern Italy and Sardegna were found to have proportions of Hb G averaging 23%. This value is considerably lower than the 34% or 48% found in Blacks from the Southeastern U.S.A. in whom the alpha G gene is in linkage with alpha-thalassemia-2, i.e. the alpha o alpha G/alpha alpha or alpha o alpha G/alpha o alpha genotypes. Gene mapping identified tandem organization of the alpha G gene in cis with a normal alpha A gene, i.e. the alpha alpha G/alpha alpha genotype, among the Hb G heterozygotes from Italy. The data on the Italian heterozygotes are similar to those obtained by Bruzdzinski et al (14) on a Black family. These results indicate alternate organization of the alpha G genes probably across racial or ethnic boundaries. Comparison of the mean cellular globin amount of alpha G/alpha G gene/cell among Hb G heterozygotes with 4, 3, 2 or 1 alpha globin genes (i.e. alpha A + alpha G) revealed considerable reactivation of individual alpha genes in conditions of mild to severe alpha globin deficiencies.

Adolescent↗
PubMed2002

Change in lung function and morbidity from chronic obstructive pulmonary disease in alpha1-antitrypsin MZ heterozygotes: A longitudinal study of the general population.

BACKGROUND: A deteriorating effect of severe alpha(1)-antitrypsin deficiency (ZZ genotype) on lung function is well known, whereas the role of intermediate deficiency (MZ genotype) remains uncertain. OBJECTIVE: To test the hypothesis that MZ intermediate alpha(1)-antitrypsin deficiency affects pulmonary function and disease. DESIGN: Population-based cohort study with 21-year follow-up. SETTING: Copenhagen, Denmark. PARTICIPANTS: 9187 adults randomly selected from the Danish general population. MEASUREMENTS: Plasma alpha(1)-antitrypsin levels, annual decrease in FEV(1), airway obstruction, and hospitalization and mortality from chronic obstructive pulmonary disease (COPD). RESULTS: 451 participants (4.9%) carried the MZ genotype. Plasma alpha(1)-antitrypsin levels were 31% lower in MZ heterozygotes than in persons with the MM genotype (Student t -test, P < 0.001). Annual decrease in FEV(1) was 25 mL in MZ heterozygotes and 21 mL in persons with the MM genotype (t -test, P = 0.048). Airway obstruction was found in 19% of MZ heterozygotes compared with 15% of MM carriers (chi-square test, P = 0.023); in a logistic regression analysis adjusted for age, sex, and tobacco consumption, the corresponding odds ratio was 1.3 (CI, 1.0 to 1.7). The incidence of hospitalization and mortality from COPD was 32 cases per 10 000 person-years in persons with the MZ genotype and 22 cases per 10 000 person-years in those with the MM genotype (log-rank test, P = 0.063). In a Cox regression model adjusted for age, sex, tobacco use, and FEV(1) at study entry, relative risk for COPD outcomes in persons with the MZ genotype versus persons with the MM genotype was 1.5 (CI, 1.0 to 2.3). All these results were independent of the S and E alleles in this gene and were not affected by cystic fibrosis Delta F508 heterozygosity. CONCLUSIONS: MZ heterozygotes had a slightly greater rate of decrease in FEV(1) and were modestly over-represented among persons with airway obstruction and COPD. In the population at large, MZ heterozygosity may account for a fraction of COPD cases---on the order of 2%, similar to the percentage of persons with COPD who have the severe but rare ZZ genotype.

Adult↗
PubMed1999

Factor V Leiden (Arg506Gln), a confounding genetic risk factor but not mandatory for the occurrence of venous thromboembolism in homozygotes and obligate heterozygotes for cystathionine beta-synthase deficiency.

Thrombosis is the major cause of morbidity and mortality in individuals with untreated classical homocystinuria (HCU) due to cystathionine beta-synthase deficiency and characterised by severe hyperhomocysteinaemia. In addition, mild and moderate hyperhomocysteinaemia and Factor V Leiden (FVL; Arg506Gln) have recently been identified as thrombotic risk factors. FVL. which renders resistance to activated Protein C, is the most common inherited genetic risk factor for thrombosis with a high allelic frequency amongst Caucasians. As thrombophilia is a multigenic disorder, 26 individuals with HCU (median age 17.6 years, range 3.5-32.8 years) and 36 obligate heterozygotes (median age 51.5 years, range 34-74 years) were screened for FVL. All the HCU individuals received treatment, except one, within 6 weeks of birth for those who were diagnosed at birth through the national newborn screening programme (n = 20) and at the time of diagnosis for those late detected (n = 5, mean age of starting treatment 4.9 years, range 1.4-11 years). All had been free from venous thrombosis, except one HCU individual and one HCU obligate heterozygote. Neither of the two individuals with venous thrombosis carried FVL. Two independent individuals with HCU (male 14.8 years; female 18.2 years) were heterozygous for FVL (allelic frequency 3.8%) and three independent HCU obligate heterozygotes (males 40 and 45.8 years; female 45.6 years) were also heterozygous for FVL (allelic frequency 4.16%). The findings in this small group suggest that FVL is not a mandatory but a significant confounding risk factor for the occurrence of thrombosis in HCU individuals and additional contributing factors may be required for thrombosis to occur in HCU obligate heterozygotes with FVL heterozygosity. Our data also suggest that treatment of HCU not only reduces the thrombotic risk in patients with isolated HCU but also in those with the additional FVL heterozygosity.

Adolescent↗
PubMed1976

[Investigation of the frequency of heterozygotes for galactose-1-phosphate-uridyl-transferase-deficiency(galactosemia) in the Vienna area. Comparison with the frequency of homozygotes found by newborn screening (author's transl)].

By routine newborn screening for galactose blood level elevations a great difference in the frequency of Galactosemia by transferase deficiency was observed between Eastern- and Western-Austria. This made enzymatic heterozygousity determinations desirable. At the same time it should be examined whether the frequency of homozygotes found by screening correlates with the frequency derived from the heterozygousity frequency. In a first step the region of Vienna was studied. 377 unselected blood samples were examined following BEUTLER-BALUDA's method. As technical control samples of 9 homozygotes and 12 heterozygotes as found by screening were examined but not included in the frequency study. Arranged following age groups a slight but significant decrease of enzym activity with increasing age could be confirmed (23,89 versus 21,99 U/g Hb). This, increasing the overlapping between normals and heterozygotes of different ages possibly should be kept in mind in individual heterzygousity determinations. The enzymatically determined frequency of heterozygotes was found to be twice as high as the frequency calculated from the frequency of biochemically detected but enzymatically proven homozygotes (1:53 versus 1:99). A comparison of the heterozygousity frequencies found in literature with the results of the most efficient (technically most reliable) screening programs shows that this discrepancy is great and general. Bases on heterozygousity frequencies the frequency of homozygotes found by screening programs seems to be at least 50% too low. Analysis of theoretical possibilities for loss of homozygotes by screening programs makes this explanation highly improbable. It seems more probable that the enzymatically determined heterozygotes frequency is too high by including still undefined allels or allel combinations which result in about half normal activity but not in disturbances resembling classical Galactosemia.

Age Factors↗
PubMed1992

Assessment of the association of HLA-DR 3/4 heterozygotes with diabetes mellitus and non-diabetic diseases.

To evaluate the disease association with HLA-DR 3/4 heterozygotes, 1,074 subjects, who had been analyzed consecutively for HLA-DR antigens for organ transplantation or to study the disease association with HLA from June 1984 to June 1986, were enrolled in this study. Of these subjects, 278 had diabetes, 168 were healthy controls or donors, and 628 had other diseases. Of the 1,074 subjects, 35 subjects (3.2%) were DR 3/4 heterozygotes and 1,039 subjects (96.7%) were non-DR 3/4 heterozygotes. Among the 35 DR 3/4 positive subjects, 23 were diabetic (65.7%), two were healthy donors (5.7%), 10 had other diseases (28.5%) such as recurrent abortion (n = 3), hepatoma (n = 2), Graves' disease (n = 1), idiopathic hypoparathyroidism (n = 1), IgA nephropathy (n = 1), uveitis (n = 1) and gout (n = 1). Among the 23 DR 3/4 positive diabetics, 19 (82.6%) had insulin-dependent diabetes mellitus (IDDM), three (13.0%) had non-insulin-dependent diabetes mellitus (NIDDM), and one (4.3%) had maturity onset diabetes of the young (MODY). When these DR 3/4 positive diabetics were compared with the other disease and control/donor groups, significant increases in the relative risk were seen for IDDM patients (RR = 32.61, 43.80, respectively, p < 0.001). No significant association could be seen for NIDDM and MODY patients. In those non-diabetic patients positive for DR 3/4, there was no significant association with DR 3/4 heterozygotes. These findings suggest that: 1) DR 3/4 positive subjects are highly associated with IDDM; and 2) there is no significant association of DR 3/4 with NIDDM, MODY and other non-diabetic diseases.

Adult↗
PubMed2004

[Beta-thalassemia mutations and single nucleotide polymorphism at -158 of Ggamma-globin gene associated with altered levels of Hb F in beta-thalassemia heterozygotes].

OBJECTIVE: To investigate the relationship of beta-thalassemia mutations and the single nucleotide polymorphism(SNP) at position -158 of (G)Gamma-globin gene to the altered levels of fetal hemoglobin(Hb F) of beta-thalassemia heterozygotes. METHODS: Hb F was quantitated by alkali denaturation; beta-thalassemia mutations were determined by PCR-allelic specific oligonucleotide(PCR-ASO). The SNP at -158 was analyzed by amplification of (G)Gamma gene promoter fragments from the DNA, followed by Xmn I restriction enzyme digestion. RESULTS: Among 63 cases with beta-thalassemia trait, 15 had Hb F levels above 2% (2.06%-10.44%). Six beta-thalassemia mutations were observed in this study, namely CD41/42(-TTCT), CD17(A-->T), nt28 (A-->G), CD71/72(+A), IVS-II-654(C-->T) and IVS-I-1(G-->T). There was no difference in the incidence of beta-thalassemia heterozygotes of CD41/42, CD17, CD71/72 and IVS-II-654 between 15 cases with Hb F>/=2% and 48 cases with Hb F<2%. Ten (15.9%) heterozygotes of (G)Gamma-158(C-->T)were detected among 63 cases, and 8 of them (53.33%) belonged to the group of Hb F>/=2% while the remaining 2 cases (4.17%) were in the group of Hb F<2%. CONCLUSION: beta-thalassemia mutations of CD41/42, CD17, CD71/72, IVS-II-654 had no influence on Hb F levels, but (G)Gamma-158(C-->T) had a strong association with moderately increased Hb F levels in beta-thalassemia heterozygotes in the Guangxi area of China.

Adult↗
PubMed1992

Mean corpuscular volume of heterozygotes for beta-thalassemia correlates with the severity of mutations.

The relationship between the degree of microcytosis and the type of mutation carried by beta-thalassemia heterozygotes was investigated. In 113 individuals, 18 different mutations were identified, correlated with mean corpuscular volume (MCV) values, and analyzed statistically. Overall, there was a wide range of MCV (56.3-87.3 fL). In almost all cases, carriers of beta(0) mutations had an MCV below 67 fL, whereas all but a few beta(+) heterozygotes had MCVs above this cutpoint. Mean MCV of beta(0) carriers was statistically significantly lower than those of beta(+) heterozygotes. The various beta(+) mutations were associated with significant differences in mean MCV values. In contrast, all the beta(0) (null) mutations had virtually identical ranges of MCV. The results indicate that degree of reduction in MCV is directly related to the severity of the mutation. Deviations, in four cases, were associated with concurrent alpha gene rearrangements, whereas in three other cases, the MCV was not significantly affected by concurrent alpha rearrangements. The MCV of beta-thalassemia heterozygotes is a valuable parameter in planning strategies for rapid identification of mutations in populations with great mutational diversity. Its use can be particularly advantageous in the setting of prenatal diagnosis. The pattern of mean corpuscular hemoglobin (MCH) values was similar to the MCV pattern. However, our results suggest that MCH may be preferred for carrier detection in population screening.

Erythrocyte Indices↗
PubMed1979

Evidence for a hybrid hexosaminidase isoenzyme in heterozygotes for Sandhoff disease.

Patients with Sandhoff disease have less than 5% of normal levels of serum or tissue hexosaminidase activity. They are thought to have a defect in the structural gene for the beta chain of hexosaminidase (HEX). Heterozygotes for Sandhoff disease have approximately 50% of the total serum HEX activity of normals and more than 75% of the HEX is heat-labile. In normals, only 55%--65% of serum HEX is heat-labile. Serum HEX separates into three forms on DEAE cellulose chromatography: HEX A, a tetramer of 2 alpha and 2 beta chains, and HEX I and B composed solely of beta chains. The DEAE chromatograms from normals and Sandhoff heterozygotes did not differ in the relative distribution of HEX activity between peaks. In normals, the HEX A peak was heat-labile (60 degrees C for 9 min), but HEX I and B were heat-stable. In Sandhoff heterozygotes, however, HEX I and B were only 50%--53% heat-stable. This suggests the heterozygotes synthesized a hybrid enzyme containing both mutant and wild-type beta chains for HEX. The mutant beta chain renders the isoenzyme less stable to heating.

Female↗
PubMed1984

Chemosensory identity of H-2 heterozygotes.

Mice can recognize the H-2 haplotypes of other mice by scent, and mice show mating preferences for partners of one H-2 type rather than another, usually for partners of an H-2 type different from their own. This olfactory sensing of H-2 odor phenotypes can favor particular H-2 types and promote H-2 diversity, at least under laboratory conditions. This is one reason why we wished to know whether the odor phenotypes of H-2 heterozygotes have distinctive features due to H-2 heterozygosity per se, because such differences could be a further vehicle for reproductive preferences promoting diversity of H-2. A more general reason for interest in the chemosensory individuality of H-2 heterozygotes is that this may shed light on the physical constitution of H-2-related odor phenotypes. The question addressed in this report is whether mice can distinguish the scent of an H-2 heterozygote from the combined scents of the constituent H-2 homozygotes. As in previous studies, the test system employed was the Y maze, in which mice are trained by water deprivation and reward to distinguish the scents of urine samples from alternative panels of donor mice. The critical distinction of the scent of heterozygotes from the combined scents of constituent homozygotes was tested by the transfer-of-training procedure, in which coded urine samples are presented to the trained mice without reward.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

[The heterozygote beta-thalassemic patient with regard to radiological hazards].

Since anaemia of varying degree is a quite common finding in heterozygous beta-thalassaemia, a research was done to see if beta-thalassaemia heterozygotes occupationally exposed to long-term continuous external radiation should be more susceptible to haematopoietic damage than non thalassaemic subjects. We examined peripheral haematological findings of 20 beta-thalassaemia heterozygotes previously exposed to a mean of 10.7 mSv, compared with 22 non thalassaemic subjects exposed to 6 mSv, and with 50 not exposed beta-thalassaemia heterozygotes. The obtained results suggest that whole-body external irradiation--with the mean doses reported--does not cause noteworthy changes in beta-thalassaemia heterozygotes.

Adolescent↗