Mackenzie's Mission Gene & Condition List
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Genetic Syndromes with an Increased Risk of Developing Cancer As an Example of the Use of New Technologies
Genetics and Molecular Biology, 37, 1 (suppl), 241-249 (2014) Copyright © 2014, Sociedade Brasileira de Genética. Printed in Brazil www.sbg.org.br Review Article Impact of NGS in the medical sciences: Genetic syndromes with an increased risk of developing cancer as an example of the use of new technologies Pablo Lapunzina1,2, Rocío Ortiz López3,4, Lara Rodríguez-Laguna2, Purificación García-Miguel5, Augusto Rojas Martínez3,4 and Víctor Martínez-Glez1,2 1Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III, Madrid, Spain. 2Instituto de Genética Médica y Molecular, Hospital Universitario la Paz, Madrid, Spain. 3Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León. Monterrey, Nuevo León, México. 4Centro de Investigación y Desarrollo en Ciencias de la Salud, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México. 5Unidad de Oncología Pediátrica, Hospital Infantil La Paz, Madrid, Spain. Abstract The increased speed and decreasing cost of sequencing, along with an understanding of the clinical relevance of emerging information for patient management, has led to an explosion of potential applications in healthcare. Cur- rently, SNP arrays and Next-Generation Sequencing (NGS) technologies are relatively new techniques used to scan genomes for gains and losses, losses of heterozygosity (LOH), SNPs, and indel variants as well as to perform com- plete sequencing of a panel of candidate genes, the entire exome (whole exome sequencing) or even the whole ge- nome. As a result, these new high-throughput technologies have facilitated progress in the understanding and diagnosis of genetic syndromes and cancers, two disorders traditionally considered to be separate diseases but that can share causal genetic alterations in a group of developmental disorders associated with congenital malformations and cancer risk. -
Megalencephaly and Macrocephaly
277 Megalencephaly and Macrocephaly KellenD.Winden,MD,PhD1 Christopher J. Yuskaitis, MD, PhD1 Annapurna Poduri, MD, MPH2 1 Department of Neurology, Boston Children’s Hospital, Boston, Address for correspondence Annapurna Poduri, Epilepsy Genetics Massachusetts Program, Division of Epilepsy and Clinical Electrophysiology, 2 Epilepsy Genetics Program, Division of Epilepsy and Clinical Department of Neurology, Fegan 9, Boston Children’s Hospital, 300 Electrophysiology, Department of Neurology, Boston Children’s Longwood Avenue, Boston, MA 02115 Hospital, Boston, Massachusetts (e-mail: [email protected]). Semin Neurol 2015;35:277–287. Abstract Megalencephaly is a developmental disorder characterized by brain overgrowth secondary to increased size and/or numbers of neurons and glia. These disorders can be divided into metabolic and developmental categories based on their molecular etiologies. Metabolic megalencephalies are mostly caused by genetic defects in cellular metabolism, whereas developmental megalencephalies have recently been shown to be caused by alterations in signaling pathways that regulate neuronal replication, growth, and migration. These disorders often lead to epilepsy, developmental disabilities, and Keywords behavioral problems; specific disorders have associations with overgrowth or abnor- ► megalencephaly malities in other tissues. The molecular underpinnings of many of these disorders are ► hemimegalencephaly now understood, providing insight into how dysregulation of critical pathways leads to ► -
KIF1A-Related Autosomal Dominant Spastic Paraplegias (SPG30) in Russian Families G
Rudenskaya et al. BMC Neurology (2020) 20:290 https://doi.org/10.1186/s12883-020-01872-4 RESEARCH ARTICLE Open Access KIF1A-related autosomal dominant spastic paraplegias (SPG30) in Russian families G. E. Rudenskaya1 , V. A. Kadnikova1* , O. P. Ryzhkova1 , L. A. Bessonova1, E. L. Dadali1 , D. S. Guseva1 , T. V. Markova1 , D. N. Khmelkova2 and A. V. Polyakov1 Abstract Background: Spastic paraplegia type 30 (SPG30) caused by KIF1A mutations was first reported in 2011 and was initially considered a very rare autosomal recessive (AR) form. In the last years, thanks to the development of massive parallel sequencing, SPG30 proved to be a rather common autosomal dominant (AD) form of familial or sporadic spastic paraplegia (SPG),, with a wide range of phenotypes: pure and complicated. The aim of our study is to detect AD SPG30 cases and to examine their molecular and clinical characteristics for the first time in the Russian population. Methods: Clinical, genealogical and molecular methods were used. Molecular methods included massive parallel sequencing (MPS) of custom panel ‘spastic paraplegias’ with 62 target genes complemented by familial Sanger sequencing. One case was detected by the whole -exome sequencing. Results: AD SPG30 was detected in 10 unrelated families, making it the 3rd (8.4%) most common SPG form in the cohort of 118 families. No AR SPG30 cases were detected. In total, 9 heterozygous KIF1A mutations were detected, with 4 novel and 5 known mutations. All the mutations were located within KIF1A motor domain. Six cases had pure phenotypes, of which 5 were familial, where 2 familial cases demonstrated incomplete penetrance, early onset and slow relatively benign SPG course. -
Clinical, Radiological, and Chondro
195 LETTER TO JMG J Med Genet: first published as 10.1136/jmg.40.3.195 on 1 March 2003. Downloaded from Clinical, radiological, and chondro-osseous findings in opsismodysplasia: survey of a series of 12 unreported cases V Cormier-Daire, A L Delezoide, N Philip, P Marcorelles, K Casas, Y Hillion, L Faivre, D L Rimoin, A Munnich, P Maroteaux, M Le Merrer ............................................................................................................................. J Med Genet 2003;40:195–200 psismodysplasia (opsismos in Greek = late) is a rare Key points chondrodysplasia, first described in 1977 by Zonana et al1 as a unique chondrodysplasia and designated O 2 “opsismodysplasia” only in 1984. The disorder is character- • We present the clinical, radiographic, and histological ised clinically by micromelia with extremely short hands and findings of 11 new cases of opsismodysplasia feet and respiratory distress responsible for death in the first belonging to eight families. few years of life.2 The main radiological features include severe • All cases presented with dysmorphic features, large platyspondyly, major delay in skeletal ossification, and anterior fontanelle, short hands and feet, and short stat- metaphyseal cupping. To date, 13 cases have been reported ure. Radiographic features included very delayed bone and recurrence in sibs and/or consanguinity have suggested maturation, marked shortness of the hand and foot an autosomal recessive mode of inheritance.1–6 Here, we bones with metaphyseal cupping and thin vertebral describe the clinical, radiological and chondro-osseous find- bodies. ings of 12 previously unreported cases in nine families. We • The outcome was variable and five children are still show that opsismodysplasia is not a consistently lethal condi- alive. -
Peds Ortho: What Is Normal, What Is Not, and When to Refer
Peds Ortho: What is normal, what is not, and when to refer Future of Pedatrics June 10, 2015 Matthew E. Oetgen Benjamin D. Martin Division of Orthopaedic Surgery AGENDA • Definitions • Lower Extremity Deformity • Spinal Alignment • Back Pain LOWER EXTREMITY ALIGNMENT DEFINITIONS coxa = hip genu = knee cubitus = elbow pes = foot varus valgus “bow-legged” “knock-knee” apex away from midline apex toward midline normal varus hip (coxa vara) varus humerus valgus ankle valgus hip (coxa valga) Genu varum (bow-legged) Genu valgum (knock knee) bow legs and in toeing often together Normal Limb alignment NORMAL < 2 yo physiologic = reassurance, reevaluate @ 2 yo Bow legged 7° knock knee normal Knock knee physiologic = reassurance, reevaluate in future 4 yo abnormal 10 13 yo abnormal + pain 11 Follow-up is essential! 12 Intoeing 1. Femoral anteversion 2. Tibial torsion 3. Metatarsus adductus MOST LIKELY PHYSIOLOGIC AND WILL RESOLVE! BRACES ARE HISTORY! Femoral Anteversion “W” sitters Internal rotation >> External rotation knee caps point in MOST LIKELY PHYSIOLOGIC AND MAY RESOLVE! Internal Tibial Torsion Thigh foot angle MOST LIKELY PHYSIOLOGIC AND WILL RESOLVE BY SCHOOL AGE Foot is rotated inward Internal Tibial Torsion (Fuchs 1996) Metatarsus Adductus • Flexible = correctible • Observe vs. casting CURVED LATERAL BORDER toes point in NOT TO BE CONFUSED WITH… Clubfoot talipes equinovarus adductus internal varus rotation equinus CAN’T DORSIFLEX cavus Clubfoot START19 CASTING JUST AFTER BIRTH Calcaneovalgus Foot • Intrauterine positioning • Resolve -
Prevalence and Incidence of Rare Diseases: Bibliographic Data
Number 1 | January 2019 Prevalence and incidence of rare diseases: Bibliographic data Prevalence, incidence or number of published cases listed by diseases (in alphabetical order) www.orpha.net www.orphadata.org If a range of national data is available, the average is Methodology calculated to estimate the worldwide or European prevalence or incidence. When a range of data sources is available, the most Orphanet carries out a systematic survey of literature in recent data source that meets a certain number of quality order to estimate the prevalence and incidence of rare criteria is favoured (registries, meta-analyses, diseases. This study aims to collect new data regarding population-based studies, large cohorts studies). point prevalence, birth prevalence and incidence, and to update already published data according to new For congenital diseases, the prevalence is estimated, so scientific studies or other available data. that: Prevalence = birth prevalence x (patient life This data is presented in the following reports published expectancy/general population life expectancy). biannually: When only incidence data is documented, the prevalence is estimated when possible, so that : • Prevalence, incidence or number of published cases listed by diseases (in alphabetical order); Prevalence = incidence x disease mean duration. • Diseases listed by decreasing prevalence, incidence When neither prevalence nor incidence data is available, or number of published cases; which is the case for very rare diseases, the number of cases or families documented in the medical literature is Data collection provided. A number of different sources are used : Limitations of the study • Registries (RARECARE, EUROCAT, etc) ; The prevalence and incidence data presented in this report are only estimations and cannot be considered to • National/international health institutes and agencies be absolutely correct. -
WES Gene Package Multiple Congenital Anomalie.Xlsx
Whole Exome Sequencing Gene package Multiple congenital anomalie, version 5, 1‐2‐2018 Technical information DNA was enriched using Agilent SureSelect Clinical Research Exome V2 capture and paired‐end sequenced on the Illumina platform (outsourced). The aim is to obtain 8.1 Giga base pairs per exome with a mapped fraction of 0.99. The average coverage of the exome is ~50x. Duplicate reads are excluded. Data are demultiplexed with bcl2fastq Conversion Software from Illumina. Reads are mapped to the genome using the BWA‐MEM algorithm (reference: http://bio‐bwa.sourceforge.net/). Variant detection is performed by the Genome Analysis Toolkit HaplotypeCaller (reference: http://www.broadinstitute.org/gatk/). The detected variants are filtered and annotated with Cartagenia software and classified with Alamut Visual. It is not excluded that pathogenic mutations are being missed using this technology. At this moment, there is not enough information about the sensitivity of this technique with respect to the detection of deletions and duplications of more than 5 nucleotides and of somatic mosaic mutations (all types of sequence changes). HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered % covered gene symbol gene ID >10x >20x >30x A4GALT [Blood group, P1Pk system, P(2) phenotype], 111400 607922 101 100 100 99 [Blood group, P1Pk system, p phenotype], 111400 NOR polyagglutination syndrome, 111400 AAAS Achalasia‐addisonianism‐alacrimia syndrome, 231550 605378 73 100 100 100 AAGAB Keratoderma, palmoplantar, -
Blueprint Genetics Craniosynostosis Panel
Craniosynostosis Panel Test code: MA2901 Is a 38 gene panel that includes assessment of non-coding variants. Is ideal for patients with craniosynostosis. About Craniosynostosis Craniosynostosis is defined as the premature fusion of one or more cranial sutures leading to secondary distortion of skull shape. It may result from a primary defect of ossification (primary craniosynostosis) or, more commonly, from a failure of brain growth (secondary craniosynostosis). Premature closure of the sutures (fibrous joints) causes the pressure inside of the head to increase and the skull or facial bones to change from a normal, symmetrical appearance resulting in skull deformities with a variable presentation. Craniosynostosis may occur in an isolated setting or as part of a syndrome with a variety of inheritance patterns and reccurrence risks. Craniosynostosis occurs in 1/2,200 live births. Availability 4 weeks Gene Set Description Genes in the Craniosynostosis Panel and their clinical significance Gene Associated phenotypes Inheritance ClinVar HGMD ALPL Odontohypophosphatasia, Hypophosphatasia perinatal lethal, AD/AR 78 291 infantile, juvenile and adult forms ALX3 Frontonasal dysplasia type 1 AR 8 8 ALX4 Frontonasal dysplasia type 2, Parietal foramina AD/AR 15 24 BMP4 Microphthalmia, syndromic, Orofacial cleft AD 8 39 CDC45 Meier-Gorlin syndrome 7 AR 10 19 EDNRB Hirschsprung disease, ABCD syndrome, Waardenburg syndrome AD/AR 12 66 EFNB1 Craniofrontonasal dysplasia XL 28 116 ERF Craniosynostosis 4 AD 17 16 ESCO2 SC phocomelia syndrome, Roberts syndrome -
Orphanet Report Series Rare Diseases Collection
Marche des Maladies Rares – Alliance Maladies Rares Orphanet Report Series Rare Diseases collection DecemberOctober 2013 2009 List of rare diseases and synonyms Listed in alphabetical order www.orpha.net 20102206 Rare diseases listed in alphabetical order ORPHA ORPHA ORPHA Disease name Disease name Disease name Number Number Number 289157 1-alpha-hydroxylase deficiency 309127 3-hydroxyacyl-CoA dehydrogenase 228384 5q14.3 microdeletion syndrome deficiency 293948 1p21.3 microdeletion syndrome 314655 5q31.3 microdeletion syndrome 939 3-hydroxyisobutyric aciduria 1606 1p36 deletion syndrome 228415 5q35 microduplication syndrome 2616 3M syndrome 250989 1q21.1 microdeletion syndrome 96125 6p subtelomeric deletion syndrome 2616 3-M syndrome 250994 1q21.1 microduplication syndrome 251046 6p22 microdeletion syndrome 293843 3MC syndrome 250999 1q41q42 microdeletion syndrome 96125 6p25 microdeletion syndrome 6 3-methylcrotonylglycinuria 250999 1q41-q42 microdeletion syndrome 99135 6-phosphogluconate dehydrogenase 67046 3-methylglutaconic aciduria type 1 deficiency 238769 1q44 microdeletion syndrome 111 3-methylglutaconic aciduria type 2 13 6-pyruvoyl-tetrahydropterin synthase 976 2,8 dihydroxyadenine urolithiasis deficiency 67047 3-methylglutaconic aciduria type 3 869 2A syndrome 75857 6q terminal deletion 67048 3-methylglutaconic aciduria type 4 79154 2-aminoadipic 2-oxoadipic aciduria 171829 6q16 deletion syndrome 66634 3-methylglutaconic aciduria type 5 19 2-hydroxyglutaric acidemia 251056 6q25 microdeletion syndrome 352328 3-methylglutaconic -
2020.07.27.20162974V1.Full.Pdf
medRxiv preprint doi: https://doi.org/10.1101/2020.07.27.20162974; this version posted July 29, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. 1 Title: Genotype and defects in microtubule-based motility correlate with clinical severity in 2 KIF1A Associated Neurological Disorder 3 Authors: Lia Boyle,1 Lu Rao,2 Simranpreet Kaur,3 Xiao Fan,1,4 Caroline Mebane,1 Laura 4 Hamm,5 Andrew Thornton,6 Jared T Ahrendsen,7 Matthew P Anderson,7,8 John Christodoulou,3 5 Arne Gennerich,2 Yufeng Shen,4,9 Wendy K Chung1,10 6 7 Abstract: KIF1A Associated Neurological Disorder (KAND) encompasses a recently identified 8 group of rare neurodegenerative conditions caused by variants in KIF1A, a member of the 9 kinesin-3 family of microtubule (MT) motor proteins. Here we characterize the natural history of 10 KAND in 117 individuals using a combination of caregiver or self-reported medical history, a 11 standardized measure of adaptive behavior, clinical records, and neuropathology. We developed 12 a heuristic severity score using a weighted sum of common symptoms to assess disease severity. 13 Focusing on 100 individuals, we compared the average clinical severity score for each variant 14 with in silico predictions of deleteriousness and location in the protein. We found increased 15 severity is strongly associated with variants occurring in regions involved with ATP and MT- 16 binding: the P-loop, switch I, and switch II. -
Rapid Publication International Nosology and Classification of Constitutional Disorders of Bone
American Journal of Medical Genetics 113:65–77 (2002) Rapid Publication International Nosology and Classification of Constitutional Disorders of Bone (2001) Christine M. Hall* Department of Radiology, Great Ormond Street Children’s Hospital, London, United Kingdom The last International Classification of Con- combination of morphological and molecular groupings stitutional Disorders of Bone was published it is anticipated that two parallel but interacting clas- in 1998. Since then rapid advances have been sifications will evolve: one clinical, identifying accepted made in identifying the molecular changes terminology or nosology, and the other molecular, to responsible for defined conditions and new help further understand the pathogenesis of individual disorders are constantly being delineated. disorders. For these reasons a further update on the The major change in the classification has been the classification is appropriate. It has been addition of genetically determined dysostoses to the expended to not only the osteochondrodys- skeletal dysplasias or osteochondrodysplasias. This is plasias (33 groups) but also genetically deter- because in clinical practice these two groups overlap. mined dysostoses (3 groups). Dysostoses may be defined as skeletal malformations ß 2002 Wiley-Liss, Inc. occurring singly or in combination. The dysostoses are static and their malformations occur during blastogen- KEY WORDS: osteochondrodysplasia; dys- esis (the first eight weeks of embryonic life). This is in ostosis; gene contrast to the skeletal dysplasias which often present after this stage, have a more general skeletal involve- ment and continue to evolve as a result of active gene The International Working Group on the Classifica- involvement throughout life. Only those dysostoses tion of Constitutional Disorders of Bone met in Oxford which have an identified chromosomal locus have been on September 4th and 5th 2001 to update the last clas- included. -
New Therapeutic Targets in Rare Genetic Skeletal Diseases
Briggs MD, Bell PA, Wright MJ, Pirog KA. New therapeutic targets in rare genetic skeletal diseases. Expert Opinion on Orphan Drugs 2015, 3(10), 1137- 1154. Copyright: ©2015 The Author(s). Published by Taylor & Francis. DOI link to article: http://dx.doi.org/10.1517/21678707.2015.1083853 Date deposited: 16/10/2015 This work is licensed under a Creative Commons Attribution 4.0 International License Newcastle University ePrints - eprint.ncl.ac.uk Expert Opinion on Orphan Drugs ISSN: (Print) 2167-8707 (Online) Journal homepage: http://www.tandfonline.com/loi/ieod20 New therapeutic targets in rare genetic skeletal diseases Michael D Briggs PhD , Peter A Bell PhD, Michael J Wright MB ChB MSc FRCP & Katarzyna A Pirog PhD To cite this article: Michael D Briggs PhD , Peter A Bell PhD, Michael J Wright MB ChB MSc FRCP & Katarzyna A Pirog PhD (2015) New therapeutic targets in rare genetic skeletal diseases, Expert Opinion on Orphan Drugs, 3:10, 1137-1154, DOI: 10.1517/21678707.2015.1083853 To link to this article: http://dx.doi.org/10.1517/21678707.2015.1083853 © 2015 The Author(s). Published by Taylor & Francis. Published online: 24 Sep 2015. Submit your article to this journal Article views: 102 View related articles View Crossmark data Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ieod20 Download by: [Newcastle University] Date: 16 October 2015, At: 07:31 Review New therapeutic targets in rare genetic skeletal diseases † Michael D Briggs , Peter A Bell, Michael J Wright & Katarzyna A Pirog † 1. Introduction Newcastle University, Institute of Genetic Medicine, International Centre for Life, Newcastle-upon-Tyne, UK 2.