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Results for “Phenotypic variability”

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At least 145 records · Page 8Linked to original sources
PubMed1997

Phenotypic variability in Friedreich ataxia: role of the associated GAA triplet repeat expansion.

We studied genotype-phenotype correlations in a group of 100 patients with typical Friedreich ataxia (FRDA), and in three groups of patients with atypical clinical presentations, including 44 Acadian FRDA, 8 late-onset FRDA (LOFA), and 6 FRDA with retained reflexes (FARR). All patients, except 3 with typical FRDA, carried two copies of the FRDA-associated GAA triplet repeat expansion. Overall, the phenotypic spectrum of FRDA appeared to be wider than defined by the currently used diagnostic criteria. Our study indicated the existence of several sources of variability in FRDA. Patients with larger GAA expansions tended to have earlier onset and were more likely to show additional manifestations of the disease. Mitotic instability of the expanded GAA repeats may partially account for the limited degree of correlation between expansion sizes as determined in lymphocytes and clinical parameters. Some clinical variants associated with specific FRDA haplotypes, such as Acadian FRDA and FARR, turned out to be unrelated to expansion sizes. No polymorphism in the frataxin coding sequence could be associated with these clinical variants.

Adolescent↗
PubMed1992

Hypothesis: Jadassohn nevus phakomatosis: a paracrinopathy with variable phenotype.

It has been postulated that the phakomatoses are paracrine growth regulation disorders (paracrinopathies). To determine how Jadassohn nevus phakomatosis (JNP) may fit such a pathogenetic model, a phenotype analysis of 13 propositi with JNP and a review of most reported JNP patients were done. The phenotypes of the propositi and the reviewed patients showed a great variability from a solitary congenital epidermal nevus to extensive cutaneous lesions with associated severe non-cutaneous anomalies. Review of long-term observations of JNP patients demonstrated considerable phenotypic changes within and beyond the boundaries of the nevi. The changes included a multitude of postnatal rare benign and/or malignant tumors and unusual manifestations: renal rickets, hepatomegaly, visceral cysts, vasculopathy, and even gangrene. Thus, a life-long predisposition to dysregulation of paracrine growth factors (GFs, regulatory peptides, peptide regulatory factors, and cytokines), foremost somatomedin-C (Sm-C, IGF-I), epidermal, fibroblast, platelet-derived GFs, and transforming GF-beta is implied. Laboratory evidence for the presumed GF dysregulation in the phakomatoses came from tissue culture study of patients with neurofibromatosis type 1 (NF-1). Compared to controls their "normal" skin showed ultrastructural changes of markedly increased number of melanin macroglobuli within the melanocytes. Paracrine GFs as relevant to hamartomatous growth were incriminated by radioimmunoassays of cutaneous neurofibromas showing two-fold or greater increase of Sm-C levels compared to the levels in the adjacent skin. Thus, NF-1 appears to be a paracrinopathy. JNP shows many more dynamic changes throughout the life span of the patients than NF-1. In the near future paracrinology may aid endocrinology and oncology in treating patients with disorders of these three growth mechanisms in man.

Adolescent↗
PubMed1998

Phenotypic variability in a family with a mitochondrial DNA T8993C mutation.

Two patients are described in a family with a mitochondrial DNA T8993C point mutation. Patient 1, the proband, was a 4-year-old male, and his clinical features were consistent with those of Leigh syndrome, including lactic acidosis, motor development delay, and symmetric basal ganglia lesions on magnetic resonance imaging (MRI). His mental development was delayed mildly, but he has not demonstrated neurologic deterioration. Patient 2 was his maternal aunt. She developed her first neurologic sign at 18 months of age, thereafter her development ceased and regressed. She had lost her head control and become bedridden by 4 years of age and died at 20 years of age, demonstrating a more severe clinical course than that of Patient 1. Analysis of mitochondrial DNA from peripheral leukocytes of Patient 1 revealed a T8993C mutation of 99%. Patient 2 was demonstrated to have the same mutation at high abundance (99%) in the frozen myocardium and in the formaldehyde preserved spinal cord, with only 18% mutant mitochondrial DNA present in the formaldehyde preserved sciatic nerve. The mother of Patient 1, who was phenotypically normal (sister of Patient 2), had 35% mutant mitochondrial DNA in peripheral leukocytes. The authors' findings suggest that T8993C phenotypes are highly variable and that the proportion of the mutant mitochondrial DNA may vary among tissues and not correlate well with clinical severity.

Base Sequence↗
PubMedDate not supplied

[Phenotypic variability of a perch parasite-cestode proteocephalus percae (Müller, 1780) (Proteocephalidea) in different parts of the species range].

Discrete variability of four P. percae characters of the main cestode functional complexes was identified. Phenotypic diversity of P. percae from different parts of the distribution range was analysed. Research revealed low geographic variability and high stability of the dominant variations in combination with morphometric plasticity. The conclusion was made that the patterns of P. percae morphological variability were shaped by the common fate and long-standing co-evolutionary relations between the parasite and the host--the perch Perca fluviatilis.

Animals↗
PubMed1999

Notable intrafamilial phenotypic variability in a kindred with familial adenomatous polyposis and an APC mutation in exon 9.

BACKGROUND: The phenotypic spectrum of familial adenomatous polyposis (FAP) varies from the classic appearance of hundreds of adenomatous colonic polyps in the young adult and early onset colorectal cancer, to the occurrence of sparse adenomas in the older adult, "attenuated" FAP, due to mutations at the 5' or 3' ends of the APC gene. AIMS: To investigate marked intrafamilial phenotypic variation occurring in a family with an APC gene mutation in exon 9. PATIENTS: An extended kindred of 22 people of whom 16 had colorectal neoplasia and/or were APC mutation carriers. RESULTS: Phenotypic manifestation varied from classic FAP to a complete lack of clinical or endoscopic, or bioptic disease in five people in three different generations. This occurred in four of them over two generations, in spite of having a confirmed 11 bp insertion causing a frame shift and stop codon (363) in exon 9 of the APC gene. CONCLUSIONS: At present, it is assumed that in this family there is alternative splicing of the APC gene, and/or unidentified modifying genetic factors. The family illustrates the importance of genetic testing in evaluating carrier status and not just clinical examination. This clinical observation also high- lights the dilemma in recognising the possible contribution of low penetrance germline APC mutations to what has been considered "sporadic" colorectal neoplasia.

Adenomatous Polyposis Coli↗
PubMed2001

Pseudohypoparathyroidism in a mother and son: phenotypic variability and associated disorder.

A 2-month-old infant with clinical features of hypothyroidism presented with hypocalcemic seizures. The maternal phenotypic features aroused the suspicion of pseudohypoparathyroidism which was confirmed in both by biochemical and endocrinological investigations. Though the child had clinical and radiological features to suggest hypothyroidism he had normal free thyroxine and only slightly elevated thyroid stimulating hormone levels. Special note is made of the intra and interpatient variability of this rare inherited disorder.

Adult↗
PubMed1994

Trichomonas vaginalis with a double-stranded RNA virus has upregulated levels of phenotypically variable immunogen mRNA.

Some isolates of Trichomonas vaginalis carry a double-stranded RNA virus (TVV) and undergo phenotypic variation between surface expression and cytoplasmic expression of a prominent immunogen (P270). Only trichomonads with TVV express P270 on the surface. Northern (RNA) blots using a specific cDNA encoding the repeat element of the phenotypically varying P270 immunogen as a probe showed accumulation of P270 transcript only in isolates with TVV (V+) in contrast to isolates without the virus (V-). To test further the influence of virus infection on P270 mRNA expression, V- progeny, derived from the parental V+ isolates, were tested. Trichomonads of V- progeny, like the fresh clinical V- isolates, also showed no accumulation of P270 mRNA. By immunoblotting with a monoclonal antibody to the key repeated epitope of P270, it was found that V- organisms had quantitatively less immunoreactive protein than the parental V+ isolates. Although V+ and V- isolates contained proteins immunoreactive with the monoclonal antibody to P270, it was necessary to test for the presence of the P270 gene among all the isolates. As expected, Southern blots demonstrated that V+ and V- trichomonads possessed the gene encoding P270. These data suggest that the double-stranded RNA virus of T. vaginalis is involved in the regulation of P270 mRNA accumulation.

Animals↗
PubMedDate not supplied

[Phenotypic variability in P. vivax with short- and long-term incubation period].

The combined transmission of P. vivax phenotypes was studied. The phenotypes were determined by the duration of a latent parasitic development stage by comparing the intervals from first manifestations of malaria with short- and long-term incubations to its relapse. The study used data on 2493 patients treated with chloroquine (900 mg base for adults) alone at follow-ups in the North-Eastern Delhi (India) in 1988-1992. The combined transmission of P. vivax phenotypes was shown to differ in malaria with short- and long-term incubation. The P. vivax phenotype with manifestations on an average a year following infection in patients with mainly short-term incubation malaria and that with manifestations on an average year and a half after infection in a group of patients with primary long-term incubation malaria were significantly more frequently. Long-term incubation malaria shows simultaneously a larger number of phenotypes than does short-term incubation one. Patients with long-term incubation malaria display a combination of 2 phenotypes (6%) significantly less frequently than that of 3 different phenotypes or more (17%). The similar combinations were observed in the equal number of patients with short-term incubation malaria (7%).

Animals↗
PubMed2006

Functional difference of the SOX10 mutant proteins responsible for the phenotypic variability in auditory-pigmentary disorders.

Waardenburg syndrome (WS) is an inherited disorder, characterized by auditory-pigmentary abnormalities. SOX10 transcription factor and endothelin receptor type B (EDNRB) are responsible for WS type 4 (WS4), which also exhibits megacolon, while microphthalmia-associated transcription factor (MITF) is responsible for WS2, which is not associated with megacolon. Here, we investigated the functions of SOX10 mutant proteins using the target promoters, EDNRB and MITF. The SOX10 mutations chosen were E189X, Q377X, and 482ins6, which are associated with WS4, and S135T that is associated with Yemenite deaf-blind hypopigmentation syndrome (YDBS), which does not manifest megacolon. These SOX10 mutant proteins showed impaired transactivation activity on the MITF promoter. In contrast, E189X and Q377X proteins, each of which lacks its C-terminal portion, activated the EDNRB promoter, whereas no activation was detected with the SOX10 proteins mutated at the DNA-binding domain, 482ins6 and S135T. However, unlike 482ins6 protein, S135T protein synergistically activated EDNRB promoter with a transcription factor Sp1, indicating that Sp1 could compensate the impaired function of a SOX10 mutant protein. We suggest that the variability in transactivation ability of SOX10 mutant proteins may account for the different phenotypes between WS4 and YDBS and that Sp1 is a potential modifier gene of WS4.

Animals↗
PubMed1998

Carrier status for steroid 21-hydroxylase deficiency is only one factor in the variable phenotype of acne.

OBJECTIVE: Previous endocrine studies of women with acne have produced diverse results. This study was designed to seek evidence, from endocrine and genetic studies, for impaired steroid biosynthesis in patients with acne. DESIGN: Adrenal stimulation tests with synthetic adrenocorticotrophic hormone (ACTH) were performed. MEASUREMENTS: Steroid hormones were measured basally and 30 minutes after ACTH. The results were correlated with analysis of the steroid 21-hydroxylase gene (CYP21). PATIENTS: Fifty-one consecutive female patients (mean age 27.1 years) referred with acne. RESULTS: The median plasma 17-hydroxyprogesterone (17-OHP) before and 30 minutes after ACTH were 2.5 nmol/l (range 1.1-8.2) and 7.3 (2.1-17.8) nmol/l which were significantly above normal female controls (n = 11, mean age 25.6 years) at 1.5 (0.9-4.2) and 4.6 (2.6-8.4) nmol/l. Eighteen of 51 acne patients showed an abnormal 17-OHP response. The 21-hydroxylase gene (CYP21) was examined for major deletions and for three common point mutations in 31 of the patients (14 with exaggerated 17-OHP response). One patient had a deletion of CYP21 on one allele consistent with carrier status for the classical congenital adrenal hyperplasia (CAH). Five patients, one of whom had a normal 17-OHP response to Synacthen, were heterozygous for the val 281 leu mutation in exon 7 of the CYP21 and were therefore carriers for a mutation associated with late-onset CAH. One patient with a raised 17-OHP response was homozygous for the splice site mutation in intron 2 and one patient with a normal 17-OHP response was heterozygous for the mutation. None of the patients had the ile 172 asn mutation. Eight of the 31 acne patients who had CYP21 gene analysis were carriers for mutations in the 21-hydroxylase gene but only six would have been detected by an abnormal response of 17-OHP on stimulation. CONCLUSION: Although alterations of the CYP21 gene were more common in acne than in controls there is a poor correlation between these events and raised steroids and acne. Factors other than mild impairment of CYP21 contribute to the variability of the clinical phenotype in hyperandrogenic states including acne.

17-alpha-Hydroxyprogesterone↗
PubMed1991

The phenotypically variable surface protein of Trichomonas vaginalis has a single, tandemly repeated immunodominant epitope.

Trichomonas vaginalis is a sexually transmitted protozoan parasite that undergoes phenotypic variation for numerous surface proteins. A monoclonal antibody (MAb) was used to isolate an approximately 400-bp cDNA encoding a fragment of an important phenotypically varying immunogen of T. vaginalis (Mr = 270 kDa; P270). The MAb completely inhibited the binding of P270 by antibody in sera of patients and by antibody in monospecific antiserum obtained toward purified P270, indicating that P270 contained only one immunodominant epitope. Hydrophilicity plot analysis of the deduced amino acid sequence of the recombinant protein predicted the hexapeptide sequence DREGRD as the antigenic determinant of P270. Synthetic peptides synthesized to this region demonstrated that the amino acid sequence DREGRD is important for antibody binding. Seven adjacent amino acids also contributed substantially to maximal recognition of the epitope by the MAb. A single transcript of approximately 9.5 kb, a size compatible with the reported Mr of the immunogen, hybridized to the cDNA in Northern blots of total RNA from T. vaginalis. DNA sequence and Southern blot analysis determined the epitope to be encoded by a 339-bp unit, which was found to be tandemly repeated at least 12 times within the single-copy gene. This 12-mer unit would only constitute approximately 50% of the protein, yet it is responsible for all of the serum antibody to the immunogen produced by animals and humans. The epitope sequence was found in all fresh and long-term-grown organisms examined to date, demonstrating the stability and conservation of this gene.

Amino Acid Sequence↗
PubMed1988

Phenotypic variability of cultured rat hepatoma cell population in respect to alpha-fetoprotein synthesis.

McA-RH 7777 hepatoma cells were cloned on 2 occasions a week apart (test cloning). Alpha-fetoprotein (AFP) phenotypes of primary and secondary clones from 55 primary clones were estimated. High interclonal heterogeneity of AFP expression was demonstrated. This variability exceeded by several orders of magnitude the mutation rate. We also found intraclonal differences in rates of variability. A "stabilizing" cloning was also carried out, aiming at the selection of AFP+ and AFP- stable cell lines. Stabilizing cloning included 7 cycles of cloning and selection of the most phenotypically stable clone. This stability was shown to be incomplete during the maintenance of clones in culture.

Animals↗
PubMed2003

The attention-deficit hyperactivity disorder paradox: 2. Phenotypic variability in prevalence and cost of comorbidity.

The objective of this study was to use population-based data to estimate the cost and phenotypic variation of conditions comorbid with attention-deficit hyperactivity disorder (ADHD). The North Dakota Department of Health's Claims Database was used to estimate the administrative prevalence, rates of comorbidity, and cost of care for subjects with ADHD. The case population was 7745 children. We then examined the 10 most frequent comorbidities for a defined condition in the International Classification of Diseases-9th edition (ICD-9). The observed prevalence of general health conditions was 12 to 70% less than expected. The presence of a comorbid condition resulted in increases in costs of care of dollar 381 to dollar 731 per case per year. The observed prevalence of comorbid mental health conditions was 97 to 5286% higher than expected. The prevalence of conditions comorbid with ADHD varies widely, with rates of general medical conditions decreased and rates of most mental disorders increased. The costs for comorbidity with general health conditions were offset by large decreases in prevalence rates compared with controls. We identified an ADHD paradox: decreased rates of comorbid general health conditions and increased rates of comorbid mental disorders. Further research on comorbidity in ADHD is required.

Attention Deficit Disorder with Hyperactivity↗
PubMed1983

Association of plasma 5'-nucleotidase and alkaline phosphatase with production traits in chickens: genetic and phenotypic variability.

Heritability of plasma alkaline phosphatase and 5'-nucleotidase enzyme activities at 20, 35 and 50 weeks of age ranged from 0.047 to 0.275. Genetic and phenotypic correlations among enzyme activities at the three ages were positive and high. Genetic correlations of enzyme activities with production traits indicated that the bird having higher activities of these enzyme will grow faster, mature earlier and produce heavier but fewer eggs.

5'-Nucleotidase↗