scholarly journals Genetic evaluation for TOR1-A (DYT1) in Brazilian patients with dystonia

2014 ◽  
Vol 72 (10) ◽  
pp. 753-756 ◽  
Author(s):  
Carlos Henrique F. Camargo ◽  
Sarah Teixeira Camargos ◽  
Salmo Raskin ◽  
Francisco Eduardo C. Cardoso ◽  
Hélio Afonso G. Teive
Keyword(s):  
Movement Disorders ◽  
Early Onset ◽  
Gene Mutations ◽  
Clinical Information ◽  
Familial History ◽  
Dyt1 Gene ◽  
History Of ◽  
Sporadic Cases ◽  
Cervical Area ◽  
Secondary Generalization

Several genes have been mapped in families or in sporadic cases of dystonia. TOR1-A (DYT1) gene was linked to isolated dystonia. Objective To associate clinical information of patients with dystonia with the TOR1-A gene mutations. Method Eighty-eight patients with dystonia in cervical area (focal, segmental, multifocal and generalized) were recruited at Movement Disorders Clinic of Hospital de Clínicas of the Federal University of Paraná between June of 2008 and June of 2009. They were submitted to the clinical evaluation. DNA was extract from blood and submitted at analysis to TOR1-A mutations by PCR according standard protocols. Results Two patients had c.907GAGdel mutation on TOR1-A gene. These patients, with familial history of dystonia, started his symptoms by legs and had secondary generalization. Conclusion We can suggest that analysis for TOR1-A mutations should be performed only in patients with early onset, generalized and familial dystonia.

scholarly journals A Familial Case of Multicentric Carpotarsal Osteolysis Syndrome and Treatment Outcome

2018 ◽  
Vol 07 (04) ◽  
pp. 174-179
Author(s):  
Alicia Gomes ◽  
Peter Weiser ◽  
Maria Descartes ◽  
Jariya Upadia
Keyword(s):  
Renal Involvement ◽  
Gene Mutations ◽  
Initial Therapy ◽  
Radiographic Examination ◽  
Inflammatory Arthropathy ◽  
Tarsal Bones ◽  
Limb Deformities ◽  
History Of ◽  
Sporadic Cases ◽  
End Stage

AbstractMulticentric carpotarsal osteolysis syndrome (MCTO) is a rare skeletal disorder caused by heterozygous mutations in the MAFB gene (v-maf musculoaponeurotic fibrosarcoma oncogene ortholog B). This is an autosomal dominant condition with a high frequency of sporadic cases. MCTO is characterized by osteolysis of the carpal, metacarpal, and tarsal bones beginning in early childhood with musculoskeletal rheumatologic symptoms such as pain and disability. Renal involvement can be seen in more than half of the patients; from ages 16 months to 42 years and manifests from proteinuria to end-stage renal failure requiring renal transplantation. The association of MAFB gene mutations with this genetic condition has aided in understanding the pathophysiology of the disease. We report here a 7-year-old Caucasian boy and his 33-year-old mother diagnosed with MCTO, with the boy having concomitant juvenile idiopathic arthritis. He was initially diagnosed with arthritis at age 5 years based on bilateral wrist synovial swelling, morning stiffness, and weakness with family history of his mother being diagnosed with erosive psoriatic arthritis leading to limb deformities. Initial therapy for the boy included methotrexate and infliximab with moderate response. Later, during the course of his disease, he underwent a genetic evaluation at age 7 years for history of learning disabilities and dysmorphic features. Maternal evaluation and radiographic examination led to a clinical diagnosis of MCTO in the mother, and subsequent testing for MAFB gene in the son revealed a mutation at c.206C > T (p.Ser69Leu), the most commonly reported genetic change in MCTO. Nevertheless, further imaging still confirmed ongoing arthritis, and therapy was adjusted based on its progression including abatacept, tocilizumab, and pamidronate. Our report highlights the possibility of concomitant inflammatory arthropathy in MCTO.

2423Familial cardiomyopathy in patients affected by acute myocarditis is strongly associated to DSP gene mutations

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
L Marteau ◽  
F Kyndt ◽  
C Toquet ◽  
J M Serfaty ◽  
D Guijarro ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Acute Myocarditis ◽  
Gene Mutations ◽  
Myocardial Inflammation ◽  
Ventricular Cardiomyopathy ◽  
Familial History ◽  
Mutation Carriers ◽  
Familial Cardiomyopathy ◽  
History Of ◽  
Familial Screening

Abstract Background The link between acute myocarditis (AM) and familial cardiomyopathy remains unclear. Purpose To assess the clinical significance of AM in families with cardiomyopathy. Methods and results We describe the pedigree of 6 families with at least one familial case of AM and a familial history of cardiomyopathy or sudden death (SD). AM was defined as an infarct-like clinical presentation with normal coronary arteries and myocardial inflammation (MI) documented by cardiac magnetic resonance (CMR), or as an autopsy proven AM. Detailed familial pedigrees are shown in the picture. In family 1 to 5, genetic testing was triggered by the association of a documented case of AM with an index case of cardiomyopathy or early SD. In this setting, all genetic testing revealed a mutation in the desmoplakin (DSP) gene. In family 1, patient II.1 (15 y.o) was diagnosed with AM, 6 months after his sister died suddenly at the age of 12. In family 2, patient II.4 (17 y.o) was diagnosed with AM. His mother had a DCM, with a CMR revealing the presence of MI. In family 3, patient IV.3 (22 y.o) died suddenly from an AM, attested by post-mortem autopsy. Her aunt had a DCM. In family 4, patient II.4 (41 y.o) had an AM, progressing toward a DCM. Her mother had died suddenly at the age of 39, and her niece had a DCM. In family 5, patient V.16 (9 y.o) presented 4 recurrent episodes of AM. Her cousin's mother had a DCM. In family 6, patient IV.3 had 3 episodes of AM, his father had previously been diagnosed with an arrythmogenic right ventricular cardiomyopathy (ARVC) with a desmoglein 2 (DSG2) mutation. Table shows detailed genotype-phenotype relationship in all mutation carriers screened in the 6 families. Phenotypes observed in mutation carriers Mutation DCM ARVC AM Isolated LGE (no cardiomyopathy, no AM) Family 1 (n=3) DSP 0 0 1 1 Family 2 (n=3) DSP 1 0 1 0 Family 3 (n=11) DSP 5 0 1 0 Family 4 (n=3) DSP 2 0 1 0 Family 5 (n=7) DSP 2 0 1 3 Family 6 (n=5) DSG2 0 1 1 1 Family Pedigrees Conclusion AM is strongly associated to desmosomal mutations when a familial history of cardiomyopathy is present, particularly in DSP gene. In these families, DCM phenotype and SD are frequent, and a notable proportion of isolated LGE suggestive of myocardial fibrosis is present in asymptomatic relatives. These results highlight the need for a comprehensive familial screening in case of AM.

Familial Malignant Hematological Disorders: A Systematic Assessment in 216 Consecutive Patients with Acute Leukaemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4500-4500
Author(s):  
Laetitia Huiart ◽  
Marina Lafage ◽  
Laetitia Rabayrol ◽  
Aude Charbonnier ◽  
Philippe Bourdeleau ◽  
...  
Keyword(s):  
Familial Cancer ◽  
Cancer Syndrome ◽  
Full Data ◽  
Familial History ◽  
Hematological Disorders ◽  
Familial Form ◽  
History Of ◽  
Sporadic Cases ◽  
Normal Cytogenetics ◽  
History Of Cancer

Abstract Purpose Our objective was to describe the biological characteristics of acute leukemia (AL) patients with or without a familial form of malignant hematological disorders. Population The study population included all newly diagnosed cases of AL treated in the departments of hematology of Institut Paoli-Calmettes between January 2002 and December 2004. We identified 291 eligible patients, of which 216 (74.2%) provided consent to participate in the study and filled a short questionnaire collecting demographic, personal and familial medical data. A face to face interview was arranged for 185 patients (85.7%) and a pedigree compiled for each family and reviewed by 2 familial cancer consultants. Results Among the 185 patients with full data on personal and familial history of cancer, 34 (18.4%) had a strong familial history of cancer of which 16 (8.6%) presented a familial form of malignant hematological disorders (at least another case of hematological malignancy in the 1, 2 or 3 degree relatives). Seven families had at least 2 first degree family members with leukemia and 2 families had 5 relatives (1st, 2nd or 3rd degree) diagnosed with leukaemia. Most index cases were diagnosed with AML in both groups (88.1%). Among familial forms, 7 AML (50%) were classified as FAB M1 or M2. No M3, M6 or M7 were identified. White blood cell count was higher than 30 G/l in 37.5% of familial form as compared to 23.5% in sporadic cases (NS). The mean circulating blast percentage was higher in familial forms (66.6% (SD= 35.5)) than in sporadic cases (36.7% (SD=32.1)) (p=0.001). None of the familial forms were consecutive to pre-existing myelodysplasic or myeloproliferative syndrome. Among familial cases with AML, 43% had normal cytogenetics (vs 36% in sporadic cases); none had a complex karyotype; one presented with a t(3;15)(p26;q11) as a mosaic, a translocation not previously reported. Complete remission (CR) rates after 1st induction and Overall Survival (OS) were similar in both groups (CR in both groups: 61.5% (n=112); OS: median: 16 months (95%CI = 10.2 – 21.8) in familial forms vs 23.9 months (18.8 – 28.9)). Conclusion According to our data, among the 15 900 new cases of AL diagnosed every year in the US, 1 370 may correspond to familial forms. This warrants awareness of clinicians who should systematically assess family cancer history. Familial AL tends to present as a proliferative form, with no prior hematologic malignancies and normal cytogenetics. This is consistent with pathogenesis pathways described in other familial cancer syndrome.

scholarly journals Prevalence of pathogenetic MC4R mutations in Italian children with early Onset obesity, tall stature and familial history of obesity

2009 ◽  
Vol 10 (1) ◽  
Author(s):  
Nicola Santoro ◽  
Grazia Cirillo ◽  
Zhimin Xiang ◽  
Rita Tanas ◽  
Nella Greggio ◽  
...  
Keyword(s):  
Early Onset ◽  
Tall Stature ◽  
Familial History ◽  
History Of ◽  
Italian Children ◽  
History Of Obesity

scholarly journals Identification of Two Dysfunctional Variants in the ABCG2 Urate Transporter Associated with Pediatric-Onset of Familial Hyperuricemia and Early-Onset Gout

2021 ◽  
Vol 22 (4) ◽  
pp. 1935
Author(s):  
Yu Toyoda ◽  
Kateřina Pavelcová ◽  
Jana Bohatá ◽  
Pavel Ješina ◽  
Yu Kubota ◽  
...  
Keyword(s):  
Early Onset ◽  
Molecular Genetic ◽  
Clinical Information ◽  
Clinical History ◽  
Coding Region ◽  
Factors Affecting ◽  
Functional Studies ◽  
Urate Transporter ◽  
History Of ◽  
Pediatric Onset

The ABCG2 gene is a well-established hyperuricemia/gout risk locus encoding a urate transporter that plays a crucial role in renal and intestinal urate excretion. Hitherto, p.Q141K—a common variant of ABCG2 exhibiting approximately one half the cellular function compared to the wild-type—has been reportedly associated with early-onset gout in some populations. However, compared with adult-onset gout, little clinical information is available regarding the association of other uricemia-associated genetic variations with early-onset gout; the latent involvement of ABCG2 in the development of this disease requires further evidence. We describe a representative case of familial pediatric-onset hyperuricemia and early-onset gout associated with a dysfunctional ABCG2, i.e., a clinical history of three generations of one Czech family with biochemical and molecular genetic findings. Hyperuricemia was defined as serum uric acid (SUA) concentrations 420 μmol/L for men or 360 μmol/L for women and children under 15 years on two measurements, performed at least four weeks apart. The proband was a 12-year-old girl of Roma ethnicity, whose SUA concentrations were 397–405 µmol/L. Sequencing analyses focusing on the coding region of ABCG2 identified two rare mutations—c.393G>T (p.M131I) and c.706C>T (p.R236X). Segregation analysis revealed a plausible link between these mutations and hyperuricemia and the gout phenotype in family relatives. Functional studies revealed that p.M131I and p.R236X were functionally deficient and null, respectively. Our findings illustrate why genetic factors affecting ABCG2 function should be routinely considered in clinical practice as part of a hyperuricemia/gout diagnosis, especially in pediatric-onset patients with a strong family history.

Shapes of Subcortical Structures in Adolescents With and Without Familial History of Substance Use Disorder

2020 ◽  
Author(s):  
Zhishun Wang ◽  
Diana V. Rodriguez Moreno ◽  
Yael M. Cycowicz ◽  
Lawrence V. Amsel ◽  
Keely Cheslack-Postava ◽  
...  
Keyword(s):  
Substance Use ◽  
Substance Use Disorder ◽  
Subcortical Structures ◽  
Familial History ◽  
History Of

scholarly journals Molecular Analysis of Targeted Insecticide Resistance Gene Mutations in Field-Caught Mosquitos of Medical Importance From Saudi Arabia

2021 ◽  
Author(s):  
Yuan Fang ◽  
Ernest Tambo ◽  
Jing-Bo Xue ◽  
Yi Zhang ◽  
Xiao-Nong Zhou ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Insecticide Resistance ◽  
Resistance Gene ◽  
Phylogenetic Analyses ◽  
Gene Mutations ◽  
Mosquito Vector ◽  
Dengue Disease ◽  
The Status ◽  
History Of ◽  
Exon 20

Abstract Gene mutations on target sites can be a valuable indicator of the status of insecticide resistance. Jeddah, a global commercial and major port-of-entry city, is bearing the brunt of dengue disease burden in Saudi Arabia. In the current study, six genotypes of three codon combinations (989, 1016, and 1534) were observed on voltage-gated sodium channel (VGSC) gene in Jeddah’s Aedes aegypti population, with PGF/PGC as the dominant one. Two types of introns between exon 20 and 21 on VGSC have been identified for the first time in Ae. aegypti in Saudi Arabia. Statistical and phylogenetic analyses showed that the intron type was significantly associated with the 1016 allele and may reflect the history of insecticide treatment in different continents. In addition, fixation of the L1014F allele on VGSC and G119S on acetylcholinesterase 1 gene was detected in local Culex quinquefasciatus populations, with frequencies of 95.24 and 100%, respectively. To the best of our knowledge, this is the first report of resistant-associated mutations in field-caught Cx. quinquefasciatus in Saudi Arabia. The high prevalence of insecticide resistance gene mutations in local primary mosquito vector species highlights the urgent need to carry out comprehensive insecticide resistance surveillance in Saudi Arabia.

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