Two New Heterozygous SF-1 Gene Mutations in Two Unrelated Families: Within-Family Phenotypic Variability during Long-Term Follow-Up in 46,XY DSD Subjects and Low Ovarian Reserve in Fertile 46,XX Subjects

2011 ◽  
Vol 76 (s1) ◽  
pp. 113-113
Author(s):  
M. Warman ◽  
M. Costanzo ◽  
R. Marino ◽  
M. Ciaccio ◽  
P. Ramirez ◽  
...  
Keyword(s):  
Ovarian Reserve ◽  
Phenotypic Variability ◽  
Gene Mutations ◽  
Long Term Follow Up ◽  
I Gene

Phenotypic Variability and Long-term Follow-up of Patients With Known and Novel PRPH2/RDS Gene Mutations

2009 ◽  
Vol 147 (3) ◽  
pp. 518-530.e1 ◽  
Author(s):  
Agnes B. Renner ◽  
Britta S. Fiebig ◽  
Bernhard H.F. Weber ◽  
Bernd Wissinger ◽  
Sten Andreasson ◽  
...  
Keyword(s):  
Phenotypic Variability ◽  
Gene Mutations ◽  
Long Term Follow Up

scholarly journals Long-Term Follow-Up of Normal Tension Glaucoma Patients With TBK1 Gene Mutations in One Large Pedigree

2020 ◽  
Vol 214 ◽  
pp. 52-62
Author(s):  
Tyler S. Quist ◽  
Chris A. Johnson ◽  
Alan L. Robin ◽  
John H. Fingert
Keyword(s):  
Gene Mutations ◽  
Normal Tension Glaucoma ◽  
Large Pedigree ◽  
Long Term Follow Up ◽  
Tbk1 Gene

scholarly journals The association between deaths from infection and mutations of the BRAF, FBXW7, NRAS and XPO1 genes: a report from the LRF CLL4 trial

Leukemia ◽  
2021 ◽  
Author(s):  
Monica Else ◽  
Stuart J. Blakemore ◽  
Jonathan C. Strefford ◽  
Daniel Catovsky
Keyword(s):  
Cause Of Death ◽  
Causes Of Death ◽  
Lymphocytic Leukaemia ◽  
Gene Mutations ◽  
Randomised Trials ◽  
Long Term Follow Up ◽  
11Q Deletion ◽  
Careful Management

AbstractCauses of death, in particular deaths due to infection, have not been widely studied in randomised trials in chronic lymphocytic leukaemia. With long-term follow-up (median 13 years) we examined the cause of death in 600/777 patients in the LRF CLL4 trial. Blood samples, taken at randomisation from 499 patients, were available for identifying gene mutations. Infection was a cause of death in 258 patients (43%). Patients dying of infection were more likely than those who died of other causes to have received ≥2 lines of treatment (194/258 [75%] versus 231/342 [68%], P = 0.04) and to have died in the winter months (149/258 [58%] versus 166/342 [49%], P = 0.03), respectively. In patients with mutation data, the factors significantly associated with death from infection versus all other deaths were 11q deletion (47/162 [29%] versus 40/209 [19%], P = 0.03) and mutations of the BRAF, FBXW7, NRAS and XPO1 genes. Death was caused by an infection in 46/67 assessable patients (69%) who had a mutation of one or more of these four genes versus only 129/333 patients (39%) without any of these mutations (odds ratio: 3.46 [95% CI 1.98–6.07] P < 0.0001). Careful management of infection risk, including prophylaxis against infection, may be important in patients who carry these mutations.

scholarly journals Penetrance of hypertrophic cardiomyopathy and outcome in sarcomeric mutation carriers

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Lorenzini ◽  
G Norrish ◽  
E Field ◽  
J.P Ochoa ◽  
M Cicerchia ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Gene Mutations ◽  
Standard Of Care ◽  
Current Standard ◽  
Mutation Carriers ◽  
Disease Penetrance ◽  
Long Term Follow Up ◽  
Few Data

Abstract Background Predictive genetic screening of the first degree relatives of patients with hypertrophic cardiomyopathy (HCM) caused by sarcomere protein (SP) gene mutations is current standard of care, but there are few data on long-term outcomes in mutation carriers without HCM. Purpose To establish the role of sex and genotype in HCM penetrance as well as the rate of major adverse clinical events in SP mutation carriers and following the diagnosis of HCM. Methods Retrospective analysis of consecutive adult and paediatric SP mutation carriers identified during family screening and who did not fulfill diagnostic criteria for HCM at first evaluation. Results 321 individuals from 170 families [median age first evaluation 15.2 years (IQR 7.3–32.6); 153 (47.7%) males] were evaluated. Causal SP genes were: MYBPC3 (n=133 (41.4%)), MYH7 (n=77 (24.0%)), TNNI3 (n=51 (15.9%)), TNNT2 (n=40 (12.5%)), TPM1 (n=9 (2.8%)), MYL2 (n=6 (1.9%)), and ACTC1 (n=1 (0.3%)); 4 (1.3%) carried multiple mutations. After a median follow up of 7.4 years (IQR 2.5–12.7), 89 (27.7%) patients developed HCM. Disease penetrance at the age of 50 years was 47% (95% CI 38%-56%). One hundred and fifty three (47.7%) individuals underwent cardiac magnetic resonance (CMR) imaging; among those diagnosed with HCM, 22/89 (24.7%) fulfilled criteria on CMR but not echocardiography. In a multivariable model adjusted for genotype, follow up duration and evaluation with CMR, independent predictors of HCM development were male sex (HR 3.11; CI 1.82–5.32) and abnormal ECG (HR 7.87; CI 4.43–13.97). Patients with MYH7 and multiple mutations were more likely to develop HCM than those with MYBPC3 mutations (HR 2.03; CI 1.04–3.96 and HR 10.13; CI 1.40–72.92, respectively). Disease penetrance was lowest in carriers of TNNI3 mutations (HR 0.13; CI 0.03–0.48). There were no major adverse events in individuals without HCM. Following the diagnosis of HCM, the combined rate of all-cause death, appropriate defibrillator shock or resuscitated cardiac arrest was 1.1%/year [median follow up 4.0 years (IQR 2.1–8.9)]. Conclusions Approximately 50% of SP mutation carriers develop HCM by the age of 50 and become prone to disease complications during long-term follow-up. Sex, MYH7 mutations and the presence of an abnormal ECG are associated with a higher risk of disease development. CMR should be employed systematically in long-term screening. HCM penetrance by sex Funding Acknowledgement Type of funding source: None

The spectrum of PIG-A gene mutations in aplastic anemia/paroxysmal nocturnal hemoglobinuria (AA/PNH): a high incidence of multiple mutations and evidence of a mutational hot spot

Blood ◽  
2003 ◽  
Vol 101 (7) ◽  
pp. 2833-2841 ◽  
Author(s):  
Yousef Mortazavi ◽  
Bruno Merk ◽  
Jenny McIntosh ◽  
Judith C. W. Marsh ◽  
Hubert Schrezenmeier ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Hot Spot ◽  
Gene Mutations ◽  
Pcr Primers ◽  
Gpi Anchor ◽  
Small Series ◽  
Long Term Follow Up

Paroxysmal nocturnal hemoglobinuria (PNH) may arise during long-term follow- up of aplastic anemia (AA), and many AA patients have minor glycosylphosphatidylinositol (GPI) anchor–deficient clones, even at presentation. PIG-A gene mutations in AA/PNH and hemolytic PNH are thought to be similar, but studies on AA/PNH have been limited to individual cases and a few small series. We have studied a large series of AA patients with a GPI anchor–deficient clone (AA/PNH), including patients with minor clones, to determine whether their pattern of PIG-A mutations was identical to the reported spectrum in hemolytic PNH. AA patients with GPI anchor–deficient clones were identified by flow cytometry and minor clones were enriched by immunomagnetic selection. A variety of methods was used to analyzePIG-A mutations, and 57 mutations were identified in 40 patients. The majority were similar to those commonly reported, but insertions in the range of 30 to 88 bp, due to tandem duplication of PIG-A sequences, and deletions of more than 10 bp were also seen. In 3 patients we identified identical 5-bp deletions by conventional methods. This prompted the design of mutation-specific polymerase chain reaction (PCR) primers, which were used to demonstrate the presence of the same mutation in an additional 12 patients, identifying this as a mutational hot spot in thePIG-A gene. Multiple PIG-A mutations have been reported in 10% to 20% of PNH patients. Our results suggest that the large majority of AA/PNH patients have multiple mutations. These data may suggest a process of hypermutation in the PIG-A gene in AA stem cells.

Long-Term Follow-Up of a Case with Dyskeratosis Congenita Caused by NHP2-V126M/X154R Mutation: Genotype-Phenotype Association

2018 ◽  
Vol 141 (1) ◽  
pp. 28-31 ◽  
Author(s):  
Melek Erdem ◽  
Özlem Tüfekçi ◽  
Şebnem Yılmaz ◽  
İnci Alacacıoğlu ◽  
Hale Ören
Keyword(s):  
Clinical Features ◽  
Bone Marrow Failure ◽  
Gene Mutations ◽  
Dyskeratosis Congenita ◽  
Compound Heterozygous ◽  
Course Of Illness ◽  
Number Of Patients ◽  
Long Term Follow Up

Dyskeratosis congenita (DC) is a rare inherited syndrome characterized by classical mucocutaneous features and the presence of other clinical features including bone marrow failure, pulmonary fibrosis, liver cirrhosis, and a predisposition to cancer. The symptoms develop at various ages and may manifest over time. Gene mutations associated with DC, such as DC1, TERC, TERT, TINF2, NHP2, NOP10, ACD, CTC1, NAF1, PARN, POT1, RTEL1, STN1, and WRAP53, have been identified in about 70% of patients. Since the number of patients with DC is small and the effect of genetic pathogenic variant may affect the phenotype, we wanted to present the clinical features and course of illness in a patient with NHP2 gene mutation (compound heterozygote for the NHP2 mutations c.376G>A/c.460T>A; amino acid substitutions: p.Val126Met and p.X154Arg) that occurred as a compound heterozygous state.

Therapy and prevention for mental health: What if mental diseases are mostly not brain disorders?

2019 ◽  
Vol 42 ◽  
Author(s):  
John P. A. Ioannidis
Keyword(s):  
Mental Health ◽  
Mental Disease ◽  
Brain Disorders ◽  
Social Stressors ◽  
Labor Education ◽  
Mental Diseases ◽  
Long Term Follow Up ◽  
Political Decisions

AbstractNeurobiology-based interventions for mental diseases and searches for useful biomarkers of treatment response have largely failed. Clinical trials should assess interventions related to environmental and social stressors, with long-term follow-up; social rather than biological endpoints; personalized outcomes; and suitable cluster, adaptive, and n-of-1 designs. Labor, education, financial, and other social/political decisions should be evaluated for their impacts on mental disease.

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