Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “genetic mutation”

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 145 records · Page 8Linked to original sources
PubMed2026

Family functioning and psychiatric outcomes in children and young people with intellectual and developmental disabilities caused by rare genetic mutations.

BACKGROUND: A range of rare chromosomal micro-deletions or -duplications (Copy Number Variants - CNVs) are associated with high risk of neurodevelopmental and mental health conditions (ND-CNVs). There is great individual variability in outcomes, but we lack insights into the contributing social factors, including family functioning. METHODS: Caregivers of 598 children and young people (CYP) with a range of 16 ND-CNVs and 222 siblings without ND-CNVs (controls) completed questionnaires on overall family climate (cohesion and conflict) as well as caregiver-CYP relationship warmth and hostility and took part in a research diagnostic interview about CYPs' psychiatric symptoms. CYPs' intelligence quotient (IQ) was also measured. RESULTS: Comparisons with published data from neurotypical families indicated that families affected by ND-CNVs are characterised by higher family cohesion and conflict as well as lower caregiver-CYP warmth and hostility. Symptoms of oppositional defiant disorder reduced more steeply in CYP with ND-CNVs compared to controls with increasing family cohesion (interaction effect: β = -0.14, p = 4.65 × 10-2). In contrast, they rose more steeply with increasing family conflict (interaction effect: β = 0.18, p = 1.05 × 10-2). Furthermore, symptoms of mood disorder increased more steeply with increased caregiver-CYP hostility in CYP with ND-CNVs (interaction effect: β = 0.15, p = 4.55 × 10-2). CONCLUSIONS: Raising a CYP with a rare genetic condition is challenging. Timely access to interventions that support caregivers in fostering a positive family environment may reduce behavioural difficulties in CYP, with subsequent benefits for family functioning.

CNV↗
PubMed1992

Sequence of exons and the flanking regions of human bilirubin-UDP-glucuronosyltransferase gene complex and identification of a genetic mutation in a patient with Crigler-Najjar syndrome, type I.

Crigler-Najjar syndrome, type I is a heterogeneous disorder that may result from mutations of various regions of the bilirubin-UDP-glucuronosyltransferase gene complex that encodes two bilirubin-UDP-glucuronosyltransferase isoforms and a phenol-UDP-glucuronosyltransferase isoform in the human liver. The two bilirubin-UDP-glucuronosyltransferase messenger RNAs and the phenol-UDP-glucuronosyltransferase messenger RNA have identical 3' regions derived from four consecutive exons. The 5' region of each messenger RNA is unique and is derived from distinct single exons. By screening a human genomic library with probes corresponding to various regions of the messenger RNAs, we have isolated five cosmid clones containing overlapping segments of this large gene complex that spans at least 84 kb of the human genome. To facilitate the amplification of each exon by polymerase chain reaction and their adjacent splice junctions, we have delineated the intron-exon boundaries of the four common region exons and the two single exons that encode the unique regions of the two bilirubin-UDP-glucuronosyltransferase isoforms and have described sequences of the regions flanking each exon. All exons encoding the two bilirubin-UDP-glucuronosyltransferase isoforms and their splice junctions were amplified from the DNA of two control subjects and a Crigler-Najjar syndrome, type I patient. The DNA from the Crigler-Najjar syndrome, type I patient revealed a point mutation in exon 3 (a common region exon) resulting in a stop codon. RNA blot showed that the two bilirubin-UDP-glucuronosyltransferase messenger RNAs in the liver of the Crigler-Najjar syndrome, type I patient were of normal length but were reduced in concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

G-proteins and hormonal signalling in human pituitary tumors: genetic mutations and functional alterations.

In the last few years, molecular studies on pituitary adenomas have yielded several lines of evidence supporting a primary pituitary origin for these tumors. In fact, analyses of x-chromosomal inactivation show that the great majority of pituitary tumors are monoclonal in origin, suggesting that one or more mutations are responsible for the selective expansion of a single cell clone. Mutations constitutively activating GTP-binding proteins have been identified in subsets of pituitary adenomas. Single amino acid substitutions replacing Arg 201 with either Cys, His, or Gln 227 with either Arg or Leu of the alpha-subunit of the Gs gene were identified in one third of growth hormone (GH)-secreting adenomas. Both mutations stabilize alpha s in its active conformation by inhibiting GTPase activity, thus mimicking the effect of specific extracellular growth factors, such as growth hormone releasing hormone (GHRH). Since several lines of evidence suggest that cAMP is involved in somatotrope replication, it has been proposed that the alpha s gene can be converted into an oncogene, designated gsp (for Gs protein). Recently, the ras oncogene has been identified in one prolactinoma characterized by unusual invasiveness. Although these data seem to negate a primary role for hypothalamic neurohormones in adenoma formation, it is conceivable that the hormones may exert a role in the sequence of events leading to clonal expansion of a transformed cell. Moreover, alterations in receptor and/or postreceptor events triggered by hypothalamic neurohormones may result in amplification of stimulatory inputs and impairment of inhibitory ones.

Animals↗
PubMed1993

Unsuccessful attempt to detect genetic mutation in tuberous sclerosis utilizing the polymerase chain reaction.

Although tuberous sclerosis is supposed to be a phacomatosis inherited as an autosomal dominant trait, many cases develop without any affected parents or grandparents. In recent years, many vigorous investigations have been concentrated on finding the mutant gene, and possible candidate genes have been mapped on 9q34 and other chromosomes. In order to find a way of diagnosing asymptomatic carriers or patients, we tried to detect restriction fragment length polymorphisms (RFLPs) using the technique of polymerase chain reaction (PCR). We used a probe, MCOA12, which is located on 9q34 and has been known to show RFLPs in Caucasian tuberous sclerosis patients. However, we could not find a correlation between the phenotype and RFLP pattern in seven of eight families.

Base Sequence↗
PubMed2000

Prevalence of prothrombin 20210A allele and methylenetetrahydrofolate reductase C677T genetic mutations in the Chinese population.

From July 1997 to June 1998, a total of 1323 subjects, including 1180 controls, 94 patients with diabetes mellitus, and 49 patients with deep-vein thrombosis, varying in age and gender, were consecutively entered into our study. Their mean (+/- SD) age was 50.0 +/- 18.0 years, range 1-99 years; 930 were male and 393 were female. None of the subjects was found to have abnormal prothrombin 20210A allele mutation. In total, 150 subjects (11.3%) were found to have a homozygous 677 C-->T mutation of the methylenetetrahydrofolate reductase gene, in which 125 were controls (10.6%), 17 were diabetics (18.1%) and 8 were patients with deep-vein thrombosis (16.3%). However, 524 subjects (39.6%) were found to have a heterozygous methylenetetrahydrofolate reductase 677 C-->T mutation. We suggested that the Chinese race dose not have the prothrombin 20210A allele, but can carry the 677 C-->T mutation of the methylenetetrahydrofolate reductase gene.

Adolescent↗
PubMed2001

Genetic mutations in exons 3 and 4 of the pancreatic secretory trypsin inhibitor in patients with pancreatitis.

PURPOSE: We hypothesized that mutations in the pancreatic secretory trypsin inhibitor (PSTI) gene could promote autodigestion, leading to acute or chronic pancreatitis. Our investigation involved mutation analysis of the PSTI gene in patients with acute or chronic pancreatitis. METHODS: Mutation analysis for the PSTI gene was performed in patients with acute or chronic pancreatitis. Unrelated healthy volunteers and family members of a chronic pancreatitis patient with point mutations in the PSTI gene were also analyzed. RESULTS: Two types of single-point mutation in the PSTI gene were observed in one patient with chronic pancreatitis: 34Asn (AAT)-to-Ser (AGT) (101 A > G N34S: N34S) in exon 3, and 67Arg (CGC)-to-Cys (TGC) (199 C > T R67C: R67C) in exon 4. No mutations with amino-acid substitution were found in other patients or in the volunteer group. In the patient with the PSTI gene mutations, no additional mutations were observed in the cationic trypsinogen gene. The family study revealed that the mother and a maternal uncle were homozygotes for the N34S mutation, while the father and brother were compound heterozygotes for the N34S and R67C mutations. The uncle (N34S/N34S) showed clinical manifestations of pancreatitis, but the other family members did not. CONCLUSIONS: The N34S mutation may cause a predisposition to pancreatitis, with incomplete penetrance. However, with the limited information available, it is not known whether the R67C mutation promotes pancreatitis.

Adolescent↗
PubMed2006

Ocular phenotype correlations in patients with TWIST versus FGFR3 genetic mutations.

BACKGROUND/PURPOSE: Despite the similar clinical phenotype of the Saethre-Chotzen and Muenke craniosynostoses, the 2 syndromes are now genotypically distinct. Patients with Saethre-Chotzen and Muenke syndromes carry mutations in the TWIST and fibroblast growth factor receptor (FGFR) 3 genes, respectively. We sought to assess possible ocular phenotypic differences in patients with mutations of either gene previously grouped according to phenotype only. METHODS: A retrospective chart review was performed for 21 children with known mutations of the TWIST (n=10) or the FGFR3 (n=11) genes. Data gathered included patient sex, age, family craniofacial history, craniofacial and ophthalmic surgeries, type of strabismus, ptosis, cycloplegic refraction, visual acuity, the presence of amblyopia, nasolacrimal duct obstruction (NLDO), nystagmus, hypertelorism, epicanthal fold anomalies, and any ocular structural abnormalities. RESULTS: In the TWIST group, ptosis was present in 90%, amblyopia in 70%, horizontal strabismus in 70%, vertical strabismus in 60%, NLDO in 60%, astigmatism in 50%, inferior oblique overaction (IOOA) in 40%, hyperopia in 40%, myopia in 30%, nystagmus in 30%, and optic nerve findings in 30%. In the FGFR3 group, ptosis was present in 36%, amblyopia in 18%, horizontal strabismus in 55%, vertical strabismus in 36%, NLDO in 0%, astigmatism in 9%, IOOA in 45%, hyperopia in 27%, myopia in 18%, nystagmus in 18%, and optic nerve findings in 27%. CONCLUSIONS: Patients with TWIST gene mutations may have more ophthalmic abnormalities, including more strabismus, ptosis, NLDO, astigmatism, vertical deviations, and amblyopia compared with patients with FGFR3 gene mutations.

Abnormalities, Multiple↗
PubMed2006

Genetic mutations in von Willebrand disease identified by DHPLC and DNA sequence analysis.

Von Willebrand disease (VWD) is a common inherited bleeding disorder caused by quantitative (types 1 and 3) and qualitative (type 2) defects in von Willebrand factor (VWF). The VWF gene is a large gene containing 52 exons; except for type 2 VWD, the majority of mutations causing VWD are not localized to specific exons. We have used denaturing high performance liquid chromatography (DHPLC) to scan the coding region of the VWF gene for sequence variations. Primers were designed to amplify all 52 exons while avoiding amplification of the VWF pseudogene. Exon-specific primers were designed with sequencing primers, allowing direct sequencing of each VWF exon. Sequence variations in 33 previously characterized von Willebrand disease (VWD) samples were all detected using DHPLC demonstrating the high sensitivity of this technique. In addition, we analyzed 42 patients or family members with VWD. Thirty-two novel sequence variations were identified (2 deletions, 2 nonsense, 15 missense, 6 silent, and 7 intronic), some with clear functional consequences. A previously described deletion in exon 18, 2435delC, was also found in two unrelated type 3 patients. This DHPLC and DNA sequencing technique will enable the full length assessment of the VWF gene necessary to detect mutations causing types 1 and 3 VWD.

Base Composition↗
PubMed2003

The implications of genetic mutations in the sodium channel gene (SCN5A).

Mutations in sodium channel alpha-subunit gene (SCN5A) result in multiple arrhythmic syndromes, including long QT3 (LQT3), Brugada syndrome (BS), an inherited cardiac conduction defect, sudden unexpected nocturnal death syndrome (SUNDS) and sudden infant death syndrome (SIDS), constituting a spectrum of disease entities termed Na+ channelopathies. These diseases are allelic disorders, if not the same disease with variable penetrance and variable modifiers worldwide. Interestingly, death occurs during sleep in all of these disorders, suggesting a common mechanism. To date, mutational analyses have revealed about 103 distinct mutations in SCN5A, of which at least more than 30 mutations are associated with LQT3, whereas the rest of the mutations are affiliated with the remaining sodium channel disorders. The majority of these mutations are missense. However, other types such as deletions, insertions, frameshifts, nonsense and splice-donor errors have also been reported.

Adult↗
PubMed2002

High-throughput, high-sensitivity genetic mutation detection by tandem single-strand conformation polymorphism/heteroduplex analysis capillary array electrophoresis.

We present the first optimization of linear polyacrylamide (LPA)-based DNA separation matrixes for an automated tandem microchannel single-strand conformation polymorphism (SSCP)/heteroduplex analysis (HA) method, implemented in capillary arrays dynamically coated with poly(N-hydroxyethylacrylamide) (polyDuramide). An optimized protocol for sample preparation allowed both SSCP and HA species to be produced in one step in a single tube and distinguished in a single electrophoretic analysis. A simple, two-color fluorescent sample labeling and detection strategy enabled unambiguous identification of all DNA species in the electropherogram, both single- and double-stranded. Using these protocols and a panel of 11 p53 mutant DNA samples in comparison with wild-type, we employed high-throughput capillary array electrophoresis (CAE) to carry out a systematic and simultaneous optimization of LPA weight-average molar mass (Mw) and concentration for SSCP/HA peak separation. The combination of the optimized LPA matrix (6% LPA, Mw 600 kDa) and a hydrophilic, adsorbed polyDuramide wall coating was found to be essential for resolution of CAE-SSCP/HA peaks and yielded sensitive mutation detection in all 11 p53 samples initially studied. A larger set of 32 mutant DNA specimens was then analyzed using these optimized tandem CAE-SSCP/HA protocols and materials and yielded 100% sensitivity of mutation detection, whereas each individual method yielded lower sensitivity on its own (93% for SSCP and 75% for HA). This simple, highly sensitive tandem SSCP/HA mutation detection method should be easily translatable to electrophoretic analyses on microfluidic devices, due to the ease of the capillary coating protocol and the low viscosity of the matrix.

Electrophoresis, Capillary↗