scholarly journals V144D Mutation ofSPTLC1Can Present with Both Painful and Painless Phenotypes in Hereditary Sensory and Autonomic Neuropathies Type I

2018 ◽  
Vol 2018 ◽  
pp. 1-3 ◽  
Author(s):  
Kwo Wei David Ho ◽  
Nivedita U. Jerath
Keyword(s):  
Autosomal Dominant ◽  
Clinical Phenotype ◽  
Point Mutations ◽  
Case Series ◽  
Sensory Loss ◽  
Type I ◽  
Dominant Disease ◽  
Underlying Causes ◽  
Lancinating Pain ◽  
Autonomic Disturbances

Hereditary sensory and autonomic neuropathy type I (HSAN I) is an autosomal dominant disease characterized by distal sensory loss, pain insensitivity, and autonomic disturbances. The major underlying causes of HSAN I are point mutations in the SPTLC1 gene. Patients with mutations in the SPTLC1 genes typically exhibit dense sensory loss and incidence of lancinating pain. Although most of these mutations produce sensory loss, it is unclear which mutations would lead to the painful phenotype. In this case series, we report that the V144D mutation in SPTLC1 gene may relate to both painful and painless peripheral neuropathies. The unique clinical phenotype of this mutation may guide clinical workup and treatment for patients with painful and painless neuropathies.

scholarly journals Clinical phenotype and genetic associations in autosomal dominant familial Alzheimer’s disease: a case series

2016 ◽  
Vol 15 (13) ◽  
pp. 1326-1335 ◽  
Author(s):  
Natalie S Ryan ◽  
Jennifer M Nicholas ◽  
Philip S J Weston ◽  
Yuying Liang ◽  
Tammaryn Lashley ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Autosomal Dominant ◽  
Clinical Phenotype ◽  
Case Series ◽  
Genetic Associations ◽  
Familial Alzheimer’S Disease ◽  
Familial Alzheimer's Disease

scholarly journals Management of Neurofibromatosis of the Nipple-Areolar Complex

2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Fahad Aljindan ◽  
Lamiaa Aljehani ◽  
Bayan Alsharif ◽  
Hatan Mortada
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Autosomal Dominant ◽  
Case Series ◽  
Surgical Excision ◽  
Neurofibromatosis Type ◽  
Nipple Areolar Complex ◽  
Areolar Complex ◽  
Dominant Disease

Neurofibromatosis type 1 is an autosomal dominant disease having an incidence of 1 in 3000 individuals. It primarily involves the peripheral nervous system and usually presents with many neurofibromas. On rare occasions, NF1 can affect the breast and manifests as nipple-areolar complex extranipple (pseudopolythelia) like neurofibromas which can be disfiguring and sometimes cause pain and therefore need to be addressed surgically. We present a case of a 31-year-old female, who had multiple pedunculated neurofibromas around the nipple on both breasts for 3 years. These lesions were associated with mild pain and were increasing in size. Surgical excision was done while preserving the nipples bilaterally. NF1 primarily involves the peripheral nervous system and usually presents with a large number of neurofibromas. Several case series of patients with NF1 have been reported, but there are only a few published reports on neurofibromas of the nipple-areolar complexes. These lesions can be painful and cause cosmetic deformity. In our case, these lesions were approached by circumferentially excising the redundant nipple-areolar skin containing the neurofibromas, while isolating the nipple on a central ductal and vascular pedicle. In conclusion, the redundant nipple-areolar skin containing the neurofibromas can simply be approached by circumferential excision while preserving the nipple. This technique is simple, easy to perform, while it allows duct preservation and preserves cosmesis.

scholarly journals Hypokalemic periodic paralysis: an underestimated autosomal-dominant disease with variable phenotypic presentations

2021 ◽  
Vol 11 (3) ◽  
pp. 7-8
Author(s):  
Kamel El-Reshaid ◽  
Shaikha Al-Bader
Keyword(s):  
Autosomal Dominant ◽  
Neurological Diseases ◽  
Gene Mutations ◽  
Periodic Paralysis ◽  
Type I ◽  
Hypokalemic Periodic Paralysis ◽  
Phenotypic Spectrum ◽  
Dominant Disease ◽  
Missed Diagnosis ◽  
Renal Tubular

Periodic paralysis (PP) diseases are autosomal dominant disorders due to gene-mutations that manifests with episodic muscle weakness and/or paralysis.  Their mutations result in faulty ion-leaks that result in sustained muscle depolarization and inexcitability.  The group include; hyperkalemic PP, hypokalemic PP (HypoPP type I & II), normokalemic PP, thyrotoxic PP, Paramyotonia congenita and Andersen-Tawil syndrome.  The hypoPP is the most common disorder yet is underestimated in prevalence due to missed diagnosis mimicking hysterical disorders and neurological diseases as well as the hypokalemic syndromes (Bartter, Gitelman and renal tubular acidosis).  Moreover, and due to their considerable gene-penetrance, their phenotypic spectrum ranges from infrequent attacks to progressive muscular failure.  In this case report we present a patient with missed diagnosis for years and describe the algorithm of his diagnosis and management. Keywords: chanellopathies, diagnosis, hypokalemia, periodic paralysis, treatment.

The Genetic Defect of Type I von Willebrand Disease “Vicenza” Is Linked to the von Willebrand Factor Gene

1993 ◽  
Vol 69 (02) ◽  
pp. 173-176 ◽  
Author(s):  
Anna M Randi ◽  
Elisabetta Sacchi ◽  
Gian Carlo Castaman ◽  
Francesco Rodeghiero ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Von Willebrand Factor ◽  
Autosomal Dominant ◽  
Genetic Defect ◽  
Von Willebrand Disease ◽  
Type I ◽  
Bleeding Tendency ◽  
Factor Gene ◽  
Low Levels ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryType I von Willebrand disease (vWD) Vicenza is a rare variant with autosomal dominant transmission, characterized by the presence of supranormal von Willebrand factor (vWF) multimers in plasma, similar to those normally found in endothelial cells and megakaryocytes. The patients have very low levels of plasma vWF contrasting with a mild bleeding tendency. The pathophysiology of this subtype is still unknown. The presence of supranormal multimers in the patients’ plasma could be due to a mutation in the vWF molecule which affects post-translational processing, or to a defect in the cells’ processing machinery, independent of the vWF molecule. In order to determne if type I vWD Vicenza is linked to the vWF gene, we studied six polymorphic systems identified within the vWF gene in two apparently unrelated families with type I vWD Vicenza. The results of this study indicate a linkage between vWF gene and the type I vWD Vicenza trait. This strongly suggests that type I vWD Vicenza is due to a mutation in one of the vWF alleles, which results in an abnormal vWF molecule that is processed to a lesser extent than normal vWF.

scholarly journals Etiologies and clinical characteristics of young patients with angle-closure glaucoma: a 15-year single-center retrospective study

2021 ◽  
Author(s):  
Feng Gao ◽  
Jiajian Wang ◽  
Junyi Chen ◽  
Xiaolei Wang ◽  
Yuhong Chen ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Anterior Segment ◽  
Young Patients ◽  
Case Series ◽  
Neovascular Glaucoma ◽  
Angle Closure Glaucoma ◽  
Angle Closure ◽  
Primary Angle Closure Glaucoma ◽  
Uncommon Presentation ◽  
Underlying Causes

Abstract Purpose To investigate the etiologies and the clinical characteristics of angle-closure glaucoma (ACG) patients younger than 40 years old in Chinese. Methods Inpatients with diagnosis of ACG and diagnosed age younger than or equal to 40 years old, who were admitted in Eye, Ear, Nose, and Throat Hospital Fudan University from 2002 to 2017, were included in this retrospective non-comparative case series. The underlying causes and clinical features for all the patients were analyzed by comprehensive review of medical charts. Results A total of 298 patients (463 eyes) met the criteria, including 153 females (51.3%) and 145 males (48.7%); the mean age was 25.6 ± 13.0 years. Primary angle-closure glaucoma (PACG), uveitis, and anterior segment dysgenesis (ASD) were the top three etiologies in our patients, which accounted for 32.6%, 20.3%, and 15.1% of the total patients respectively. PACG mainly occurs after 30 years of age and ASD is the top reason of ACG in patients younger than 20 years old. Other known etiologies include iridocorneal endothelial syndrome, neovascular glaucoma, nanophthalmos, retinitis pigmentosa, spherophakia, bestrophinopathy, persistent fetal vasculature, iridociliary cysts, congenital retinoschisis, Marfan’s syndrome, retinopathy of prematurity, familial exudative vitreoretinopathy, congenital retinal folds, Coat’s disease, and neurofibromatosis. Conclusions We described the uncommon presentation of ACG in Chinese young patients. Although unusual, most of the etiologies could be identified. Therefore, more careful and comprehensive examinations are needed for early detection and timely treatment for young ACG patients.

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.

Cartilage Regeneration with Cell-free Type 1 Collagen Matrix – Past, Present and Future (Part 1 – Clinical Aspects)

2020 ◽  
Author(s):  
Philip Peter Roessler ◽  
Turgay Efe ◽  
Dieter Christian Wirtz ◽  
Frank Alexander Schildberg
Keyword(s):  
Type I Collagen ◽  
Case Series ◽  
Cartilage Regeneration ◽  
Collagen Matrix ◽  
Treatment Method ◽  
Collagen Type I ◽  
Legal Framework ◽  
Clinical Aspects ◽  
Type I ◽  
Collagen Hydrogel

AbstractCartilage regeneration with cell-free matrices has developed from matrix-associated autologous cartilage cell transplantation (MACT) over ten years ago. Adjustments to the legal framework and higher hurdles for cell therapy have led to the procedures being established as an independent alternative to MACT. These procedures, which can be classified as matrix-induced autologous cartilage regeneration (MACR), all rely on the chemotactic stimulus of a cross-linked matrix, which mostly consists of collagens. Given the example of a commercially available type I collagen hydrogel, the state of clinical experience with MACR shall be summarized and an outlook on the development of the method shall be provided. It has been demonstrated in the clinical case series summarized here over the past few years that the use of the matrix is not only safe but also yields good clinical-functional and MR-tomographic results for both small (~ 10 mm) and large (> 10 mm) focal cartilage lesions. Depending on the size of the defect, MACR with a collagen type I matrix plays an important role as an alternative treatment method, in direct competition with both: microfracture and MACT.

scholarly journals Expanding the genetic spectrum of primary familial brain calcification due to SLC2OA2 mutations: a case series

Neurogenetics ◽  
2021 ◽  
Author(s):  
Luca Magistrelli ◽  
Roberta Croce ◽  
Fabiola De Marchi ◽  
Chiara Basagni ◽  
Miryam Carecchio ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Case Series ◽  
Dominant Trait ◽  
Autosomal Dominant Trait ◽  
Phenotypic Spectrum ◽  
Primary Familial Brain Calcification ◽  
Psychiatric Disturbances ◽  
Brain Calcification ◽  
Uncertain Significance ◽  
Six Genes

AbstractPrimary familial brain calcification (PFBC) is a neurological condition characterized by the presence of intracranial calcifications, mainly involving basal ganglia, thalamus, and dentate nuclei. So far, six genes have been linked to this condition: SLC20A2, PDGFRB, PDGFB, and XPR1 inherited as autosomal-dominant trait, while MYORG and JAM2 present a recessive pattern of inheritance. Patients mainly present with movement disorders, psychiatric disturbances, and cognitive decline or are completely asymptomatic and calcifications may represent an occasional finding. Here we present three variants in SLC20A2, two exonic and one intronic, which we found in patients with PFBC associated to three different clinical phenotypes. One variant is novel and two were already described as variants of uncertain significance. We confirm the pathogenicity of these three variants and suggest a broadening of the phenotypic spectrum associated with mutations in SLC20A2.

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