keyword
MENU ▼
Read by QxMD icon Read
search

Missense variants & pathogenicity prediction

keyword
https://www.readbyqxmd.com/read/29034544/cyp2u1-activity-is-altered-by-missense-mutations-in-hereditary-spastic-paraplegia-56
#1
Christelle M Durand, Laura Dhers, Christelle Tesson, Alessandra Tessa, Laetitia Fouillen, Stéphanie Jacqueré, Laure Raymond, Isabelle Coupry, Giovanni Benard, Frédéric Darios, Khalid H El-Hachimi, Guja Astrea, François Rivier, Guillaume Banneau, Claire Pujol, Didier Lacombe, Alexandra Durr, Patrick J Babin, Filippo M Santorelli, Nicolas Pietrancosta, Jean-Luc Boucher, Daniel Mansuy, Giovanni Stevanin, Cyril Goizet
Hereditary Spastic Paraplegia (HSP) is an inherited disorder of the central nervous system mainly characterized by gradual spasticity and weakness of the lower limbs. SPG56 is a rare autosomal recessive early onset complicated form of HSP caused by mutations in CYP2U1. The CYP2U1 enzyme was shown to catalyze the hydroxylation of arachidonic acid. Here, we report two further SPG56 families carrying 3 novel CYP2U1 missense variants and the development of an in vitro biochemical assay to determine the pathogenicity of missense variants of uncertain clinical significance...
October 16, 2017: Human Mutation
https://www.readbyqxmd.com/read/29028823/novel-mutations-in-darier-disease-and-association-to-self-reported-disease-severity
#2
Ivone U S Leong, Alexander Stuckey, Tara Ahanian, Martin Cederlöf, Jakob D Wikstrom
Darier disease is a rare and severe autosomal dominant skin disease characterised by malodorous keratotic papules in seborrheic areas of the skin. Darier disease affects up to 1 in 30 000 people and is caused by mutations in the ATP2A2 gene, which encodes to the sarco/endoplasmic reticulum calcium-ATPase isoform 2 that pumps calcium into the endoplasmic reticulum. Although many ATP2A2 variants have been described, it is not known if genotype correlates with phenotype, which could be important for prognosis and treatment...
2017: PloS One
https://www.readbyqxmd.com/read/28965847/hypomorphic-recessive-variants-in-sufu-impair-the-sonic-hedgehog-pathway-and-cause-joubert-syndrome-with-cranio-facial-and-skeletal-defects
#3
Roberta De Mori, Marta Romani, Stefano D'Arrigo, Maha S Zaki, Elisa Lorefice, Silvia Tardivo, Tommaso Biagini, Valentina Stanley, Damir Musaev, Joel Fluss, Alessia Micalizzi, Sara Nuovo, Barbara Illi, Luisa Chiapparini, Lucia Di Marcotullio, Mahmoud Y Issa, Danila Anello, Antonella Casella, Monia Ginevrino, Autumn Sa'na Leggins, Susanne Roosing, Romina Alfonsi, Jessica Rosati, Rachel Schot, Grazia Maria Simonetta Mancini, Enrico Bertini, William B Dobyns, Tommaso Mazza, Joseph G Gleeson, Enza Maria Valente
The Sonic Hedgehog (SHH) pathway is a key signaling pathway orchestrating embryonic development, mainly of the CNS and limbs. In vertebrates, SHH signaling is mediated by the primary cilium, and genetic defects affecting either SHH pathway members or ciliary proteins cause a spectrum of developmental disorders. SUFU is the main negative regulator of the SHH pathway and is essential during development. Indeed, Sufu knock-out is lethal in mice, and recessive pathogenic variants of this gene have never been reported in humans...
October 5, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28965491/compound-heterozygous-mutations-in-uba5-causing-early-onset-epileptic-encephalopathy-in-two-sisters
#4
Gudny A Arnadottir, Brynjar O Jensson, Sigurdur E Marelsson, Gerald Sulem, Asmundur Oddsson, Ragnar P Kristjansson, Stefania Benonisdottir, Sigurjon A Gudjonsson, Gisli Masson, Gudmundur A Thorisson, Jona Saemundsdottir, Olafur Th Magnusson, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Asgeir Sigurdsson, Daniel F Gudbjartsson, Unnur Thorsteinsdottir, Reynir Arngrimsson, Patrick Sulem, Kari Stefansson
BACKGROUND: Epileptic encephalopathies are a group of childhood epilepsies that display high phenotypic and genetic heterogeneity. The recent, extensive use of next-generation sequencing has identified a large number of genes in epileptic encephalopathies, including UBA5 in which biallelic mutations were first described as pathogenic in 2016 (Colin E et al., Am J Hum Genet 99(3):695-703, 2016. Muona M et al., Am J Hum Genet 99(3):683-694, 2016). UBA5 encodes an activating enzyme for a post-translational modification mechanism known as ufmylation, and is the first gene from the ufmylation pathway that is linked to disease...
October 2, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28965043/a-novel-pax9-mutation-causing-oligodontia
#5
Eiman Mohammed Daw, Christian Saliba, Godfrey Grech, Simon Camilleri
INTRODUCTION: An extended family presenting with several members affected by developmentally missing teeth was investigated by analysis of the MSX1 and PAX9 genes. MATERIALS AND METHODS: Saliva samples were collected and DNA extracted. Primers were designed to span the exons and intron-exon junctions of the MSX1 and PAX9 genes. These primers were optimised using gradient Polymerase Chain Reaction. The amplified fragments were sent for Sanger sequencing RESULTS: a novel heterozygote missense mutation in exon 3 of PAX9 (c...
September 25, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28950846/analysis-of-the-vsx1-gene-in-sporadic-keratoconus-patients-from-china
#6
Tao Guan, Xue Wang, Li-Bin Zheng, Hai-Jian Wu, Yu-Feng Yao
BACKGROUND: Keratoconus normally presents as a sporadic disease. Although different studies have found sequence variants of the visual system homeobox 1 (VSX1) gene associated with keratoconus in humans, no research has detected such variants in sporadic keratoconus patients from China. To investigate the possibility of VSX1 being a candidate susceptibility gene for Chinese patients with sporadic keratoconus, we performed sequence screening of this gene in such patients. METHODS: Whole DNA was obtained from the leukocytes in the peripheral venous blood of 50 patients with sporadic keratoconus and 50 control subjects without this ocular disorder...
September 26, 2017: BMC Ophthalmology
https://www.readbyqxmd.com/read/28950840/diagnostic-challenge-in-a-patient-with-nephropathic-juvenile-cystinosis-a-case-report
#7
Satomi Higashi, Natsuki Matsunoshita, Masako Otani, Etsuro Tokuhiro, Kandai Nozu, Shuichi Ito
BACKGROUND: Cystinosis is a rare autosomal recessive lysosomal disorder characterized by the accumulation of cystine in lysosomes. Cystinosis is much rarer in Asian than Caucasian populations. There are only 14 patients have with cystinosis alive in Japan. Most cystinosis is the nephropathic infantile form, as indicated by its apparent and severe clinical manifestations, including renal and ocular symptoms. Patients with the nephropathic juvenile form account for 5% of those with cystinosis...
September 26, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28946916/prevalence-of-tecta-mutation-in-patients-with-mid-frequency-sensorineural-hearing-loss
#8
Nobuko Yamamoto, Hideki Mutai, Kazunori Namba, Noriko Morita, Shin Masuda, Yasuyuki Nishi, Atsuko Nakano, Sawako Masuda, Masato Fujioka, Kimitaka Kaga, Kaoru Ogawa, Tatsuo Matsunaga
BACKGROUND: To date, 102 genes have been reported as responsible for non-syndromic hearing loss, some of which are associated with specific audiogram features. Four genes have been reported as causative for mid-frequency sensorineural hearing loss (MFSNHL), among which TECTA is the most frequently reported; however, the prevalence of TECTA mutations is unknown. To elucidate the prevalence of TECTA mutation in MFSNHL and clarify genotype-phenotype correlations, we analyzed the genetic and clinical features of patients with MFSNHL...
September 25, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28945736/rapid-functional-analysis-of-computationally-complex-rare-human-irf6-gene-variants-using-a-novel-zebrafish-model
#9
Edward B Li, Dawn Truong, Shawn A Hallett, Kusumika Mukherjee, Brian C Schutte, Eric C Liao
Large-scale sequencing efforts have captured a rapidly growing catalogue of genetic variations. However, the accurate establishment of gene variant pathogenicity remains a central challenge in translating personal genomics information to clinical decisions. Interferon Regulatory Factor 6 (IRF6) gene variants are significant genetic contributors to orofacial clefts. Although approximately three hundred IRF6 gene variants have been documented, their effects on protein functions remain difficult to interpret. Here, we demonstrate the protein functions of human IRF6 missense gene variants could be rapidly assessed in detail by their abilities to rescue the irf6 -/- phenotype in zebrafish through variant mRNA microinjections at the one-cell stage...
September 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28911202/pathogenicity-of-a-novel-missense-variant-associated-with-choroideremia-and-its-impact-on-gene-replacement-therapy
#10
Simona Torriano, Nejla Erkilic, Valérie Faugère, Krishna Damodar, Christian P Hamel, Anne-Francoise Roux, Vasiliki Kalatzis
Choroideremia (CHM) is an inherited retinal dystrophy characterised by progressive degeneration of photoreceptors, retinal pigment epithelium (RPE) and underlying choroid. It is caused by loss-of-function mutations in CHM, which has an X-linked inheritance, and is thus an ideal candidate for gene replacement strategies. CHM encodes REP1, which plays a key role in the prenylation of Rab GTPases. We recently showed that an induced pluripotent stem cell (iPSc)-derived RPE model for CHM is fully functional and reproduces the underlying prenylation defect...
September 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28911001/whole-exome-analysis-of-a-li-fraumeni-family-trio-with-a-novel-tp53-prd-mutation-and-anticipation-profile
#11
Sara Franceschi, Laura Spugnesi, Paolo Aretini, Francesca Lessi, Rosa Scarpitta, Alvaro Galli, Caterina Congregati, Maria Adelaide Caligo, Chiara Maria Mazzanti
Li-Fraumeni syndrome is a clinically heterogeneous familial cancer predisposition syndrome with autosomal-dominant inheritance caused by heterozygous germline mutations in the TP53 gene. We here analyze the genetic background of a family with a 4-year-proband presented with a Li-Fraumeni tumor. The mother developed breast cancer at age 37 and the proband died at age 8. We performed Sanger sequencing and whole-exome sequencing on peripheral blood DNA from proband and relatives. Data analysis selected only high-quality score and depth reads, rare variants and protein impact involving missense, non-sense, frameshift and splice disrupt mutations...
September 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28910730/pathogenic-and-likely-pathogenic-genetic-alterations-and-polymorphisms-in-growth-hormone-gene-gh1-and-growth-hormone-releasing-hormone-receptor-gene-ghrhr-in-a-cohort-of-isolated-growth-hormone-deficient-ighd-children-in-sri-lanka
#12
Tharmini Sundralingam, Kamani Hemamala Tennekoon, Shamya de Silva, Sumadee De Silva, Asanka Sudeshini Hewage
OBJECTIVE: Genetic alterations in GH1 and GHRHR genes are known to cause isolated growth hormone deficiency (IGHD). Of these, GHRHR codon 72 mutation has been reported to be highly prevalent in the Indian subcontinent, but among Sri Lankans its prevalence was low compared to reports from neighboring countries. The present study was therefore carried out to identify genetic alterations in the GH1 gene and rest of the GHRHR gene in a cohort of Sri Lankan IGHD patients who tested negative for GHRHR codon 72 mutation...
September 5, 2017: Growth Hormone & IGF Research
https://www.readbyqxmd.com/read/28875386/novel-spg20-mutation-in-an-extended-family-with-troyer-syndrome
#13
S Bizzari, A R Hamzeh, P Nair, M Mohamed, F Saif, G Aithala, M T Al-Ali, F Bastaki
Troyer Syndrome (TRS) is a rare autosomal recessive complicated spastic paraplegia disorder characterized by various neurological and musculoskeletal manifestations. Pathogenicity stems from mutations in SPG20 which encodes Spartin, a multifunctional protein that is thought to be essential for neuron viability. Here we report on the clinical and molecular characterization of TRS in five patients from an extended consanguineous family in the United Arab Emirates. Molecular analysis involved Whole Exome Sequencing and Sanger sequencing for identification and confirmation of the causative variant respectively...
September 5, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28867931/targeted-next-generation-sequencing-analysis-identifies-novel-mutations-in-families-with-severe-familial-exudative-vitreoretinopathy
#14
Xiao-Yan Huang, Hong Zhuang, Ji-Hong Wu, Jian-Kang Li, Fang-Yuan Hu, Yu Zheng, Laurent Christian Asker M Tellier, Sheng-Hai Zhang, Feng-Juan Gao, Jian-Guo Zhang, Ge-Zhi Xu
PURPOSE: Familial exudative vitreoretinopathy (FEVR) is a genetically and clinically heterogeneous disease, characterized by failure of vascular development of the peripheral retina. The symptoms of FEVR vary widely among patients in the same family, and even between the two eyes of a given patient. This study was designed to identify the genetic defect in a patient cohort of ten Chinese families with a definitive diagnosis of FEVR. METHODS: To identify the causative gene, next-generation sequencing (NGS)-based target capture sequencing was performed...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28866361/targeted-next-generation-sequencing-of-glandular-odontogenic-cyst-a-preliminary-study
#15
Elisa Carvalho de Siqueira, Silvia Ferreira de Sousa, Josiane Alves França, Marina Gonçalves Diniz, Thaís Dos Santos Fontes Pereira, Rennan Garcias Moreira, Pablo Agustin Vargas, Ricardo Santiago Gomez, Carolina Cavalieri Gomes
OBJECTIVE: Glandular odontogenic cyst (GOC) is an uncommon developmental cyst. Its molecular pathogenesis is unclear, and deep sequencing may help identify causative low-frequency variants in tumors. We investigated in GOC mutations in 50 genes commonly altered in human cancers. STUDY DESIGN: Targeted next-generation sequencing was used to interrogate a panel of approximately 2800 mutations in GOC. RESULTS: Six missense single nucleotide variations (SNVs) were reported...
July 26, 2017: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/28864920/discovery-of-mutations-in-homologous-recombination-genes-in-african-american-women-with-breast-cancer
#16
Yuan Chun Ding, Aaron W Adamson, Linda Steele, Adam M Bailis, Esther M John, Gail Tomlinson, Susan L Neuhausen
African-American women are more likely to develop aggressive breast cancer at younger ages and experience poorer cancer prognoses than non-Hispanic Caucasians. Deficiency in repair of DNA by homologous recombination (HR) is associated with cancer development, suggesting that mutations in genes that affect this process may cause breast cancer. Inherited pathogenic mutations have been identified in genes involved in repairing DNA damage, but few studies have focused on African-Americans. We screened for germline mutations in seven HR repair pathway genes in DNA of 181 African-American women with breast cancer, evaluated the potential effects of identified missense variants using in silico prediction software, and functionally characterized a set of missense variants by yeast two-hybrid assays...
September 2, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28864458/optimizing-genomic-medicine-in-epilepsy-through-a-gene-customized-approach-to-missense-variant-interpretation
#17
Joshua Traynelis, Michael Silk, Quanli Wang, Samuel F Berkovic, Liping Liu, David B Ascher, David J Balding, Slavé Petrovski
Gene panel and exome sequencing have revealed a high rate of molecular diagnoses among diseases where the genetic architecture has proven suitable for sequencing approaches, with a large number of distinct and highly penetrant causal variants identified among a growing list of disease genes. The challenge is, given the DNA sequence of a new patient, to distinguish disease-causing from benign variants. Large samples of human standing variation data highlight regional variation in the tolerance to missense variation within the protein-coding sequence of genes...
October 2017: Genome Research
https://www.readbyqxmd.com/read/28862263/neurofibromin-c-terminus-specific-antibody-clone-nfc-is-a-valuable-tool-for-the-identification-of-nf1-inactivated-gists
#18
Sabrina Rossi, Daniela Gasparotto, Matilde Cacciatore, Marta Sbaraglia, Alessia Mondello, Maurizio Polano, Alessandra Mandolesi, Alessandro Gronchi, David E Reuss, Andreas von Deimling, Roberta Maestro, Angelo Paolo Dei Tos
An increasing body of evidence supports the involvement of NF1 mutations, constitutional or somatic, in the pathogenesis of gastrointestinal stromal tumors (GISTs). Due to the large size of the NF1 locus, the existence of multiple pseudogenes and the wide spectrum of mechanisms of gene inactivation, the analysis of NF1 gene status is still challenging for most laboratories. Here we sought to assess the efficacy of a recently developed neurofibromin-specific antibody (NFC) in detecting NF1-inactivated GISTs...
September 1, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28837161/biallelic-variants-in-lingo1-are-associated-with-autosomal-recessive-intellectual-disability-microcephaly-speech-and-motor-delay
#19
Muhammad Ansar, Saima Riazuddin, Muhammad Tahir Sarwar, Periklis Makrythanasis, Sohail Aziz Paracha, Zafar Iqbal, Jamshed Khan, Muhammad Zaman Assir, Mureed Hussain, Attia Razzaq, Daniel Lôpo Polla, Abid Sohail Taj, Asbjørn Holmgren, Naila Batool, Doriana Misceo, Justyna Iwaszkiewicz, Arjan P M de Brouwer, Michel Guipponi, Sylviane Hanquinet, Vincent Zoete, Federico A Santoni, Eirik Frengen, Jawad Ahmed, Sheikh Riazuddin, Hans van Bokhoven, Stylianos E Antonarakis
PurposeTo elucidate the novel molecular cause in two unrelated consanguineous families with autosomal recessive intellectual disability.MethodsA combination of homozygosity mapping and exome sequencing was used to locate the plausible genetic defect in family F162, while only exome sequencing was followed in the family PKMR65. The protein 3D structure was visualized with the University of California-San Francisco Chimera software.ResultsAll five patients from both families presented with severe intellectual disability, aggressive behavior, and speech and motor delay...
August 24, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28831623/structural-consequences-of-mutations-associated-with-idiopathic-restrictive-cardiomyopathy
#20
Svetlana Tarnovskaya, Artem Kiselev, Anna Kostareva, Dmitrij Frishman
Idiopathic restrictive cardiomyopathy (RCM, MIM# 115210) is the least common type of cardiomyopathies, often of genetic origin. Recently we described a spectrum of variants-classified as pathogenic, likely pathogenic and variants of unknown significance-in 24 patients suffering from idiopathic RCM. Pathogenic variants, detected in half of the RCM cases, were found in sarcomeric and cytoskeletal genes that have a predominant role in the development of RCM. Here we have analyzed the structural consequences of these missense variants and predicted their effect on the function of three large groups of domains: intrinsically disordered regions (IDRs), fibronectin-type III (FnIII) domains, and immunoglobulin-like (Ig) domains...
August 22, 2017: Amino Acids
keyword
keyword
19415
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"