Search results for "Mutation"

F9 missense mutations impairing factor IX activation are associated with pleiotropic plasma phenotypes.

2022

Background Circulating dysfunctional factor IX (FIX) might modulate distribution of infused FIX in hemophilia B (HB) patients. Recurrent substitutions at FIX activation sites (R191-R226, >300 patients) are associated with variable FIX activity and antigen (FIXag) levels. Objectives To investigate the (1) expression of a complete panel of missense mutations at FIX activation sites and (2) contribution of F9 genotypes on the FIX pharmacokinetics (PK). Methods We checked FIX activity and antigen and activity assays in plasma and after recombinant expression of FIX variants and performed an analysis of infused FIX PK parameters in patients (n = 30), mostly enrolled in the F9 Genotype and PK HB …

Increase in viral gastroenteritis outbreaks in Europe and epidemic spread of new norovirus variant.

2004

Background Highly publicised outbreaks of norovirus gastroenteritis in hospitals in the UK and Ireland and cruise ships in the USA sparked speculation about whether this reported activity was unusual. Methods We analysed data collected through a collaborative research and surveillance network of viral gastroenteritis in ten European countries (England and Wales were analysed as one region). We compiled data on total number of outbreaks by month, and compared genetic sequences from the isolated viruses. Data were compared with historic data from a systematic retrospective review of surveillance systems and with a central database of viral sequences. Findings Three regions (England and Wales,…

Descriptive study on subjective experience of genetic testing with respect to relationship, family planning and psychosocial wellbeing among women wi…

2021

AbstractBackgroundDue to increased risk of endometrial and ovarian cancer, women belonging to known Lynch Syndrome (LS) families are recommended to undergo germline testing. Current practice in Finland is to offer counselling to women with pathogenic variant and advocate risk-reducing surgery (RRS) after completion of childbirth. The present study aimed to clarify the impacts of positive germline testing on family planning and reproductive decisions of these women, which are relatively unknown.MethodsSeventy-nine carriers of germline MMR gene pathogenic variant (path_MMR)were identified from the Finnish LS Registry as having genetic testing performed before the age of 45 years and not havin…

Amplicon-based high-throughput pooled sequencing identifies mutations in CYP7B1 and SPG7 in sporadic spastic paraplegia patients

2011

Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder defined clinically by progressive lower limb spasticity and weakness. HSP is a genetically highly heterogeneous condition with at least 46 gene loci identified so far, involving X-linked, autosomal recessive (AR) and autosomal dominant inheritance. For correct diagnosis, molecular testing is essential because clinical parameters by themselves are not reliable to differentiate HSP forms. The purpose of this study was to establish amplicon-based high-throughput genotyping for AR-HSP. A sample of 187 index cases with apparently sporadic or recessive spastic paraplegia were analyzed by applying an array-based amplification stra…

Does the evidence matter in medicine? The retinoblastoma paradigm.

2007

Retinoblastoma (Rb) is the most common intraocular malignant tumour in childhood, with an incidence of 1 in 15,000 live births. Complete information on this rare tumour can be easily accessed through the internet, although many aspect concerning the aetiology and pathogenesis of the disease, are still controversial. The "two hit" theory, formulated in 1971 to explain the variegated clinical expression of the disease, is based on the idea that single gene mutation may determine the development of cancer. However, this view does not take into account the most recent evidences showing the role of aneuploidy and chromosome instability in cancer. Also, a number of other genes and epigenetic mech…

FUNCTIONAL EFFECT OF NOVEL AMINO ACID VARIANTS OF APOLIPOPROTEIN B IN FAMILIAL HYPOBETALIPOPROTEINEMIA

2011

Introduction. Familial Hypobetalipoproteinemia (FHBL) is a codominant disorder characterized by reduced plasma levels of LDL-C and apolipoprotein (apo) B. In 50% of cases FHBL is due to mutations in APOB gene resulting in truncated apoBs of various size. Some mutations in APOB gene resulting in non-conservative amino acid substitutions were reported to cause FHBL. In vitro, these mutations induce the retention of the mutant apoB in the endoplasmic reticulum (ER) and impair the secretion of apoB-containing lipoproteins. In two FHBL subjects we identified two novel amino acid variants (Thr26_27delinsAsn and Tyr102Cys) located in the N-terminal 1000 amino acids of mature apoB. Methods. To inve…

Mutacje w mitochondrialnym DNA i reaktywne formy tlenu jako czynniki wpływające na procesy starzenia się komórek i organizmów

2016

A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma

2011

International audience; So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes; risk factors associated with RCC include smoking, obesity and hypertension. A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers. The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene; it also stimulates the transcription of hypoxia inducible factor (HIF1A), the pathway of which is targeted by kidney canc…

Does δ-sarcoglycan-associated autosomal-dominant cardiomyopathy exist?

2009

In this study we clinically and genetically characterize a consanguineous family with a homozygous novel missense mutation in the delta-sarcoglycan gene and a second delta-sarcoglycan mutation that has previously been reported to cause severe autosomal-dominant dilated cardiomyopathy. We identified a novel missense mutation in exon 6 (p.A131P) of the delta-sarcoglycan gene, which in a homozygous state leads to the clinical picture of a limb girdle muscular dystrophy. In four heterozygous carriers for the mutation, aged 3-64 years, a second sequence variant in exon 6 (p.S151A) of the delta-sarcoglycan gene was detected on the other allele. This second missense change had previously been repo…

Pfeiffer syndrome: clinical and genetic findings in five Brazilian families

2014

Pfeiffer syndrome (PS) is mainly characterized by craniosysnostosis, midface hypoplasia, great toes with partial syndactyly of the digits and broad and medially deviated thumbs. It is caused by allelic mutations in the fibroblast growth factor receptor 1 and 2 (FGFR1 and 2) genes. This study describes the clinical and genetic features of five Brazilian families affected by PS. All patients exhibited the classical phenotypes related to PS. The genetic analysis was able to detect the mutations Cys278Phe, Cys342Arg, and Val359Leu in three of these families. Two mutations were de novo, with one familial. We identified pathogenic mutations in four PS cases in five Brazilian families by PCR seque…