scholarly journals A Novel Mutation in TSC2 Gene: A 34-Year-Old Female with Pulmonary Lymphangioleiomyomatosis with Concomitant Hepatic Lesions

2018 ◽  
Vol 2018 ◽  
pp. 1-3 ◽  
Author(s):  
Mehdi Nadiri ◽  
Mortaza Raeisi ◽  
Seyed Ali Mousavi Aghdas
Keyword(s):  
Autosomal Dominant ◽  
Novel Mutation ◽  
Reproductive Age ◽  
Response To Treatment ◽  
Tsc2 Gene ◽  
Pulmonary Lymphangioleiomyomatosis ◽  
Dominant Disease ◽  
Hepatic Lesions ◽  
The Impact ◽  
The Brain

Tuberous sclerosis complex (TSC) is an autosomal dominant disease resulting from mutation(s) in TSC1 or TSC2 genes. TSC is associated with the formation of hamartomas in the brain, heart, eyes, skin, kidneys, and lymphangioleiomyomatosis (LAM) of the lungs. LAM is almost restricted to women in reproductive age. Different mutations in TSC1 and TSC2 genes have been reported in the literature. Here, we present a female patient with TSC-LAM with a novel mutation in TSC2 gene. The patient also had multiple hepatic angiomyolipomas, which is a relatively less-reported manifestation of the disease. The impact of this mutation on the pattern of disease presentation and response to treatment is not clear yet.

scholarly journals A novel TSC1 variant associated with tuberous sclerosis and sacrococcygeal teratoma

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Saba Ahmad ◽  
Luis Manon ◽  
Gifty Bhat ◽  
Jerry Machado ◽  
Alice Zalan ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Cellular Differentiation ◽  
Autosomal Dominant ◽  
De Novo ◽  
Autosomal Dominant Disease ◽  
Sacrococcygeal Teratoma ◽  
Dominant Disease ◽  
The Brain

AbstractTuberous sclerosis complex (TSC) is an autosomal dominant disease associated with tumors and malformed tissues in the brain and other vital organs. We report a novel de novo frameshift variant of the TSC1 gene (c.434dup;p. Ser146Valfs*8) in a child with TSC who initially presented with a sacral teratoma. This previously unreported association between TSC and teratoma has broad implications for the pathophysiology of embryonic tumors and mechanisms underlying cellular differentiation.

scholarly journals A hereditaer nonpolyposus colorectalis carcinoma szindrómás betegek szűrésének és szoros utánkövetésének fontossága egy családfa bemutatása kapcsán

2017 ◽  
Vol 158 (30) ◽  
pp. 1182-1187
Author(s):  
Gergely Kóder ◽  
Judit Olasz ◽  
László Tóth ◽  
Hilda Urbancsek ◽  
Csilla András ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Novel Mutation ◽  
Family Members ◽  
Her Family ◽  
Mmr Genes ◽  
Gene Mutation Carrier ◽  
Hereditary Nonpolyposis ◽  
Dominant Disease ◽  
Associated Tumors

Abstract: Introduction: Hereditary nonpolyposis colorectal carcinoma (HNPCC) is an autosomal dominant disease, which shows familial clustering. Aim: We would like to emphasize the importance of monitoring the HNPCC syndrome patients by presenting a case of a proven MMR gene mutation carrier and her family tree encompassing 10 years. Materials and method: To screen a suspected HNPCC Hungarian family member we are taking thorough family histories. If the diagnosis of HNPCC was further supported by immunohistology and the microsatellite status, sequencing of the MMR genes was carried out. Results: A novel mutation in exon 6 of the hMSH2 gene leading to the deletion of two nucleotide pairs [c.969-970delTC] was detected in our patient. During the 10-year follow-up period of our patient new HNPCC-associated tumors have developed in several family members. Conslusion: Close surveillance of the patient and its family members at risk was effective, although it requires compliance from the subjects. Orv Hetil. 2017; 158(30): 1182–1187.

scholarly journals RHOMutations (p.W126L and p.A346P) in Two Japanese Families with Autosomal Dominant Retinitis Pigmentosa

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Satoshi Katagiri ◽  
Takaaki Hayashi ◽  
Masakazu Akahori ◽  
Takeshi Itabashi ◽  
Jo Nishino ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Retinitis Pigmentosa ◽  
Autosomal Dominant ◽  
Conformational Transition ◽  
Novel Mutation ◽  
The Novel ◽  
Autosomal Dominant Retinitis Pigmentosa ◽  
Modeling Analysis ◽  
Whole Exome ◽  
The Impact

Purpose. To investigate genetic and clinical features of patients with rhodopsin (RHO) mutations in two Japanese families with autosomal dominant retinitis pigmentosa (adRP).Methods. Whole-exome sequence analysis was performed in ten adRP families. IdentifiedRHOmutations for the cosegregation analysis were confirmed by Sanger sequencing. Ophthalmic examinations were performed to evaluate the RP phenotypes. The impact of theRHOmutation on the rhodopsin conformation was examined by molecular modeling analysis.Results. In two adRP families, we identified twoRHOmutations (c.377G>T (p.W126L) and c.1036G>C (p.A346P)), one of which was novel. Complete cosegregation was confirmed for each mutation exhibiting the RP phenotype in both families. Molecular modeling predicted that the novel mutation (p.W126L) might impair rhodopsin function by affecting its conformational transition in the light-adapted form. Clinical phenotypes showed that patients with p.W126L exhibited sector RP, whereas patients with p.A346P exhibited classic RP.Conclusions. Our findings demonstrated that the novel mutation (p.W126L) may be associated with the phenotype of sector RP. Identification ofRHOmutations is a very useful tool for predicting disease severity and providing precise genetic counseling.

scholarly journals Familial neurohypophyseal diabetes insipidus due to a novel mutation in the arginine vasopressin–neurophysin II gene

2011 ◽  
Vol 165 (1) ◽  
pp. 161-165 ◽  
Author(s):  
M de Fost ◽  
A S P van Trotsenburg ◽  
H M van Santen ◽  
E Endert ◽  
C van den Elzen ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Water Deprivation ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Resonance Imaging ◽  
Exon 2 ◽  
Hyperintense Signal ◽  
The Brain ◽  
Neurophysin Ii

BackgroundFamilial neurohypophyseal (central) diabetes insipidus (DI) is caused by mutations in the arginine vasopressin–neurophysin II (AVP–NPII) gene. The majority of cases is inherited in an autosomal dominant way. In this study, we present the clinical features of a mother and her son with autosomal dominant neurohypophyseal DI caused by a novel mutation.CaseA thirty-four-year-old woman and her three-year-old son were evaluated because of polyuria and polydipsia since the age of 1.5 years onwards. Both patients were subjected to a water deprivation test confirming the diagnosis of central DI. Magnetic resonance imaging of the brain of the mother showed a hypothalamus without apparent abnormalities and a relatively small neurohypophysis without a hyperintense signal. Mutation analysis showed a c.322G>T (p.?/p.Glu108X) in Exon 2 of the AVP–NPII gene in both mother and son.DiscussionThis study reports neurohypophyseal DI in a mother and her son due to a novel mutation in Exon 2 of the AVP–NPII gene. Clinical and pathophysiological aspects of this disease are shortly reviewed and discussed.

scholarly journals Novel Mutation in CACNA1A Associated with Activity-Induced Dystonia, Cervical Dystonia, and Mild Ataxia

2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Benjamin Stampfl ◽  
Dominic Fee
Keyword(s):  
Cervical Dystonia ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Genetic Diagnosis ◽  
Cerebellar Atrophy ◽  
Familial Hemiplegic Migraine ◽  
Spinocerebellar Ataxia Type ◽  
Spinocerebellar Ataxia Type 6 ◽  
History Of ◽  
The Brain

CACNA1A encodes the pore-forming α1 subunit of the neuronal voltage-gated Cav2.1 (P/Q-type) channels, which are predominantly localized at the presynaptic terminals of the brain and cerebellar neurons and play an important role in controlling neurotransmitter release. Mutations in CACNA1A have been associated with several autosomal dominant neurologic disorders, including familial hemiplegic migraine type 1, episodic ataxia type 2 (EA2), and spinocerebellar ataxia type 6. A 37-year-old woman presented with a history of slowly progressive, activity-induced stiffness, and pain in her right leg since age 15 and cervical dystonia since age 20. She denied any right leg stiffness or pain at rest, but when she began to walk, her right foot turned in and her right leg stiffened up. She also had neck pain, stiffness, and spams. There was no family history of similar symptoms. On physical exam, her strength, tone, and reflexes were normal in all extremities at rest. There was mild head titubation and very mild past pointing on finger-to-nose testing. MRI of the brain and spinal cord was unremarkable. This patient’s clinical picture was felt to be most consistent with paroxysmal kinesigenic dyskinesia, as she has attacks of dystonia that are triggered by voluntary movement, last from a few seconds to a minute, and are relieved with rest. She was trialed on carbidopa/levodopa without improvement. A dystonia panel showed two potentially pathologic mutations, one in CACNA1A and the other in PNKP, along with a variant of unknown significance in ATP7B. The mutation in CACNA1A is C2324 G < A. It is heterozygous, autosomal dominant, and computer modeling suggests pathogenicity. This mutation has not been reported previously and is likely the cause of her paroxysmal dystonia; dystonia is sometimes seen during episodes of ataxia in EA2, and CACNA1A knockout mice exhibit dystonia and cerebellar atrophy. After receiving her genetic diagnosis, the patient was trialed on acetazolamide without improvement in her dystonia symptoms. This is the second case report of a patient with cervical dystonia and cerebellar ataxia associated with a mutation in CACNA1A.

scholarly journals 8q22.1 Microduplication Syndrome: Why the Brain Should Be Spared? A Literature Review and a Case Report

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Antonella Gagliano ◽  
Erica Pironti ◽  
Francesca Cucinotta ◽  
Cecilia Galati ◽  
Roberta Maggio ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Psychiatric Symptoms ◽  
Disease Risk ◽  
Positive Family History ◽  
Bipolar Disorders ◽  
Psychiatric Illnesses ◽  
Skeletal Malformations ◽  
Dominant Disease ◽  
The Brain ◽  
Rare Autosomal Dominant Disease

Microduplication of chromosome 8q22.1 is mainly associated to Leri’s pleonosteosis syndrome phenotype, an extremely rare autosomal dominant disease encompassing the GDF6 and SDC2 genes. To date, most of the authors focus their attention only on skeletal symptoms of the disease, and they do not systematically research or describe the co-occurrence of psychiatric illnesses or mental disorders with these muscular-skeletal diseases. In this report, we provide a description of an 8-year-old girl, with a positive family history for both skeletal malformations and bipolar disorders (BD). We suggest a possible association between Leri’s pleonosteosis features and psychiatric symptoms. Furthermore, our report could be added to the large amount of reports that describe the correlation between genetic regions and disease risk for both psychiatric and rheumatological disorders.

scholarly journals Prospects for Diminishing the Impact of Nonamyloid Small-Vessel Diseases of the Brain

2020 ◽  
Vol 60 (1) ◽  
pp. 437-456
Author(s):  
Anne Joutel
Keyword(s):  
Critical Appraisal ◽  
Autosomal Dominant ◽  
Vascular Risk Factor ◽  
The Elderly ◽  
Small Vessel ◽  
Therapeutic Approaches ◽  
Intracerebral Hemorrhages ◽  
Heavy Burden ◽  
The Impact ◽  
The Brain

Small-vessel diseases (SVDs) of the brain are involved in about one-fourth of ischemic strokes and a vast majority of intracerebral hemorrhages and are responsible for nearly half of dementia cases in the elderly. SVDs are a heavy burden for society, a burden that is expected to increase further in the absence of significant therapeutic advances, given the aging population. Here, we provide a critical appraisal of currently available therapeutic approaches for nonamyloid sporadic SVDs that are largely based on targeting modifiable risk factors. We review what is known about the pathogenic mechanisms of vascular risk factor–related SVDs and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most frequent hereditary SVD, and elaborate on two mechanism-based therapeutic approaches worth exploring in sporadic SVD and CADASIL. We conclude by discussing opportunities and challenges that need to be tackled if efforts to achieve significant therapeutic advances for these diseases are to be successful.

scholarly journals Tuberous Sclerosis as a cause of difficult-to-control Epilepsy - Case report

2020 ◽  
Vol 1 (5) ◽  
pp. 73-77
Author(s):  
Walter Leonardo Alves Gusmão ◽  
◽  
Antonio Marcos da Silva Catharino ◽  
Keyword(s):  
Tuberous Sclerosis ◽  
Autosomal Dominant ◽  
Significant Proportion ◽  
Intractable Epilepsy ◽  
Skin Lesions ◽  
Clinical Criteria ◽  
Multisystem Involvement ◽  
High Penetrance ◽  
Dominant Disease ◽  
The Brain

Tuberous Sclerosis Complex or Bourneville’s disease is an autosomal dominant disease with high penetrance and variability characterized by multisystem involvement by benign lesions, originally defined by the classic triad of Vogt: sebaceous adenoma, epilepsy and mental retardation. The involvement of the brain is responsible for a significant proportion of the morbidity and mortality of this disease and skin lesions are the most common manifestations. The authors report 31-year-old patient case referred to the service by intractable epilepsy with definitive clinical criteria for tuberous sclerosis.

scholarly journals A family harboring an MLKL loss of function variant implicates impaired necroptosis in diabetes

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Joanne M. Hildebrand ◽  
Bernice Lo ◽  
Sara Tomei ◽  
Valentina Mattei ◽  
Samuel N. Young ◽  
...  
Keyword(s):  
Potential Role ◽  
Autosomal Dominant ◽  
Inflammatory Diseases ◽  
Diabetic Patients ◽  
Incomplete Penetrance ◽  
Loss Of Function ◽  
Healthy Sibling ◽  
Dominant Disease ◽  
Terminal Effector

AbstractMaturity-onset diabetes of the young, MODY, is an autosomal dominant disease with incomplete penetrance. In a family with multiple generations of diabetes and several early onset diabetic siblings, we found the previously reported P33T PDX1 damaging mutation. Interestingly, this substitution was also present in a healthy sibling. In contrast, a second very rare heterozygous damaging mutation in the necroptosis terminal effector, MLKL, was found exclusively in the diabetic family members. Aberrant cell death by necroptosis is a cause of inflammatory diseases and has been widely implicated in human pathologies, but has not yet been attributed functions in diabetes. Here, we report that the MLKL substitution observed in diabetic patients, G316D, results in diminished phosphorylation by its upstream activator, the RIPK3 kinase, and no capacity to reconstitute necroptosis in two distinct MLKL−/− human cell lines. This MLKL mutation may act as a modifier to the P33T PDX1 mutation, and points to a potential role of impairment of necroptosis in diabetes. Our findings highlight the importance of family studies in unraveling MODY’s incomplete penetrance, and provide further support for the involvement of dysregulated necroptosis in human disease.

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