检索结果-内蒙古大学图书馆

The value of age of onset and family history as predictors of molecular diagnosis in a Swedish cohort of inherited retinal disease

引用

ACTA OPHTHALMOLOGICA 2025年第3期103卷 327-338页

作者： De Geer, Karl Lofgren, Stefan Lindstrand, Anna kvarnung, malin Bjorck, Erik Karolinska Inst Dept Mol Med & Surg S-17176 Stockholm Sweden Karolinska Univ Hosp Dept Clin Genet & Genom Stockholm Sweden Karolinska Inst Dept Clin Neurosci Div Ophthalmol & Vis Stockholm Sweden St Erik Eye Hosp Stockholm Sweden

PurposeThis study aimed to characterize clinical and genetic findings in a Swedish cohort with inherited retinal disease (IRD), identify predictors for achieving a molecular diagnosis and evaluate the effects of increased genetic testing over *** and genetic data from 324 nonrelated IRD index individuals referred for genetic testing in the Stockholm region between 2016 and 2023 were collected retrospectively and analysed by clinical subtype, age of onset and testing period (2016-2020 vs. 2021-2023). Logistic regression was used to calculate odds ratios for age of onset and family history on the likelihood of achieving a molecular *** diagnostic yield was 55% and involved 56 genes. In 10% of solved individuals, the molecular diagnosis refined the clinical diagnosis. For each 1-year increase in age of onset, the odds of achieving a molecular diagnosis decreased by 3% (odds ratio 0.97, 95% confidence interval 0.96-0.98). A positive family history doubled the odds (odds ratio 2.1, 95% confidence interval 1.3-3.4). The use of genetic testing increased 2.1-fold and the number of molecular diagnoses increased 1.6-fold relative to the population of the Stockholm region between the two testing *** study adds to the knowledge of the clinical and genetic landscape of IRDs in Sweden and establishes age of onset and family history as significant predictors for achieving a molecular diagnosis. Increased genetic testing on a population level substantially increased the number of individuals receiving a molecular diagnosis with a high diagnostic yield compared to other rare diseases.

关键词： age of onset eye diseases genomics retinal dystrophies

来源：评论

学校读者我要写书评

暂无评论

Unraveling GRIA1 neurodevelopmental disorders: Lessons learned from the p.(Ala636Thr) variant

引用

CLINICAL GENETICS 2024年第4期106卷 427-436页

作者： Tvergaard, Nicolai Kohring Tkemaladze, Tinatin Stodberg, Tommy kvarnung, malin Tatton-Brown, Katrina Baralle, Diana Tumer, Zeynep Bayat, Allan Copenhagen Univ Hosp Kennedy Ctr Rigshosp Dept Clin Genet Blegdamsvej 9 DK-2100 Copenhagen Denmark Tbilisi State Med Univ Dept Mol & Med Genet Tbilisi Georgia Tbilisi State Med Univ Dept Pediat Givi Zhvania Pediat Acad Clin Tbilisi Georgia Karolinska Inst Dept Womens & Childrens Hlth Stockholm Sweden Karolinska Univ Hosp Dept Pediat Neurol Stockholm Sweden Karolinska Inst Dept Mol Med & Surg Stockholm Sweden Karolinska Univ Hosp Dept Clin Genet Stockholm Sweden Univ London St Georges Univ Hosp NHS Fdn Trust & St Georges London England Univ Hosp Southampton NHS Fdn Trust Princess Anne Hosp Wessex Clin Genet Serv Southampton England Univ Southampton Southampton Gen Hosp Fac Med Duthie Bldg Southampton England Univ Copenhagen Fac Hlth & Med Sci Dept Clin Med Copenhagen Denmark Univ Copenhagen Dept Drug Design & Pharmacol Copenhagen Denmark Danish Epilepsy Ctr Dept Epilepsy Genet & Personalized Med Dianalund Denmark Univ Southern Denmark Dept Reg Hlth Res Odense Denmark

Ionotropic glutamate receptors (iGluRs), specifically alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs), play a crucial role in orchestrating excitatory neurotransmission in the brain. AMPARs are intricate assemblies of subunits encoded by four paralogous genes: GRIA1-4. Functional studies have established that rare GRIA variants can alter AMPAR currents leading to a loss- or gain-of-function. Patients affected by rare heterozygous GRIA variants tend to have family specific variants and only few recurrent variants have been reported. We deep-phenotyped a cohort comprising eight unrelated children and adults, harboring a recurrent and well-established disease-causing GRIA1 variant (NM_001114183.1: c.1906G>A, p.(Ala636Thr)). Recurrent symptoms included motor and/or language delay, mild-severe intellectual disability, behavioral and psychiatric comorbidities, hypotonia and epilepsy. We also report challenges in social skills, autonomy, living and work situation, and occupational levels. Furthermore, we compared their clinical manifestations in relation to those documented in patients presenting with rare heterozygous variants at analogous positions within paralogous genes. This study provides unprecedented details on the neurodevelopmental outcomes, cognitive abilities, seizure profiles, and behavioral abnormalities associated with p.(Ala636Thr) refining and broadening the clinical phenotype.

关键词： AMPAR autonomy developmental trajectory epilepsy GRIA1 natural history outcome syndrome treatment

来源：评论

学校读者我要写书评

暂无评论

Multi-omics analysis detail a submicroscopic inv(15)(q14q15) generating fusion transcripts and MEIS2 and NUSAP1 haploinsufficiency

引用

SCIENTIFIC REPORTS 2024年第1期14卷 1-7页

作者： Ek, Marlene kvarnung, malin Pettersson, Maria Soller, Maria Johansson Anderlid, Britt-Marie Thonberg, Hakan Eisfeldt, Jesper Lindstrand, Anna Karolinska Inst Dept Mol Med & Surg S-17176 Stockholm Sweden Karolinska Univ Hosp Dept Clin Genet & Genom S-17176 Stockholm Sweden Karolinska Inst Sci Pk Sci Life Lab S-17165 Solna Sweden

Inversions are balanced structural variants that often remain undetected in genetic diagnostics. We present a female proband with a de novo Chromosome 15 paracentric inversion, disrupting MEIS2 and NUSAP1. The inversion was detected by short-read genome sequencing and confirmed with adaptive long-read sequencing. The breakpoint junction analysis revealed a 96 bp (bp) deletion and an 18 bp insertion in the two junctions, suggesting that the rearrangement arose through a replicative error. Transcriptome sequencing of cultured fibroblasts revealed normal MEIS2 levels and 0.61-fold decreased expression of NUSAP1. Furthermore, three fusion transcripts were detected and confirmed by Sanger sequencing. Heterozygous loss of MEIS2 (MIM# 600987) is associated with a cleft palate, heart malformations, and intellectual impairment, which overlap with the clinical symptoms observed in the proband. The observed fusion transcripts are likely non-functional, and MEIS2 haploinsufficiency is the likely disease causative mechanism. Altogether, this study's findings illustrate the importance of including inversions in rare disease diagnostic testing and highlight the value of long read sequencing for the validation and characterization of such variants.

关键词： Inversion Short-read whole genome sequencing Adaptive long-read sequencing Transcriptome sequencing MEIS2 Gene disruption Gene fusion

来源：评论

学校读者我要写书评

暂无评论

Identification of biallelic POLA2 variants in two families with an autosomal recessive telomere biology disorder

引用

EUROPEAN JOURNAL OF HUMAN GENETICS 2025年第5期33卷 580-587页

作者： kvarnung, malin Pettersson, Maria Chun-on, Pattra Rafati, Maryam Mcreynolds, Lisa J. Norberg, Anna Moura, Pedro Luis Pesonen, Ida Chaireti, Roza Soderholm, Boa Gronros Burlin, Julia Ryden, Jenny Lindberg, Eva Hellstroem Giri, Neelam Savage, Sharon A. Agarwal, Suneet Nordgren, Ann Tesi, Bianca Karolinska Inst Dept Mol Med & Surg Stockholm Sweden Karolinska Univ Hosp Clin Genet & Genom Stockholm Sweden Boston Childrens Hosp Dept Pediat Div Hematol Oncol Boston MA USA Harvard Med Sch Dana Farber Canc Inst Pediat Oncol Boston MA USA NCI Div Canc Epidemiol & Genet Clin Genet Branch Bethesda MD USA Umea Univ Dept Med Biosci Med & Clin Genet Umea Sweden Karolinska Inst Ctr Hematol & Regenerat Med Dept Med Huddinge Stockholm Sweden Karolinska Inst Dept Med Solna Resp Med Unit Stockholm Sweden Karolinska Univ Hosp Dept Resp Med & Allergy Stockholm Sweden Karolinska Univ Hosp Dept Hematol Stockholm Sweden Karolinska Inst Dept Med Solna Stockholm Sweden Danderyd Hosp Div Nephrol Stockholm Sweden Sahlgrens Univ Hosp Dept Clin Genet & Genom Gothenburg Sweden Univ Gothenburg Sahlgrenska Acad Inst Biomed Dept Lab Med Gothenburg Sweden Karolinska Univ Hosp Genom Med Ctr Karolinska Stockholm Sweden

POLA2 encodes the accessory subunit of DNA polymerase alpha (pol alpha)/primase, which is crucial for telomere C-strand fill-in. Incomplete fill-in of the C-rich telomeric strand after DNA replication has been proposed as a mechanism for Coats plus syndrome, a phenotype within the broader spectrum of telomere biology disorders (TBD). Coats plus syndrome has so far been associated with pathogenic variants in POT1, CTC1, and STN1. Here we report the findings of biallelic deleterious rare variants in POLA2 gene detected by whole genome sequencing and segregation analysis in five young adults from two unrelated families. All five individuals displayed abnormally short telomeres and a clinical phenotype suggesting a TBD disorder with Coats plus features including retinal and gastrointestinal telangiectasias. Our results suggest POLA2 as a novel autosomal recessive gene for a TBD with Coats plus features.

关键词：

来源：评论

学校读者我要写书评

暂无评论

Genome sequencing is a sensitive first-line test to diagnose individuals with intellectual disability

引用

GENETICS IN MEDICINE 2022年第11期24卷 2296-2307页

作者： Lindstrand, Anna Ek, Marlene kvarnung, malin Anderlid, Britt-Marie Bjoerck, Erik Carlsten, Jonas Eisfeldt, Jesper Grigelioniene, Giedre Gustavsson, Peter Hammarsjoe, Anna Helgadottir, Hafdis T. Hellstroem-Pigg, Maritta Kuchinskaya, Ekaterina Lagerstedt-Robinson, Kristina Levin, Lars-Ake Lieden, Agne Lindeloef, Hillevi Malmgren, Helena Nilsson, Daniel Svensson, Eva Paucar, Martin Sahlin, Ellika Tesi, Bianca Tham, Emma Winberg, Johanna Winerdal, Max Wincent, Josephine Soller, Maria Johansson Pettersson, Maria Nordgren, Ann Karolinska Inst Dept Mol Med & Surg Stockholm Sweden Karolinska Univ Hosp Dept Clin Genet SE-17176 Stockholm Sweden Karolinska Inst Dept Mol Med & Surg Sci Life Lab Solna Sweden Linkoping Univ Dept Hlth Med & Caring Sci Linkoping Sweden Karolinska Univ Hosp Dept Pediat Neurol Huddinge Sweden

Purpose: Individuals with intellectual disability (ID) and/or neurodevelopment disorders (NDDs) are currently investigated with several different approaches in clinical genetic diagnostics. Methods: We compared the results from 3 diagnostic pipelines in patients with ID/NDD: genome sequencing (GS) first (N = 100), GS as a secondary test (N = 129), or chromosomal microarray (CMA) with or without FMR1 analysis (N = 421). Results: The diagnostic yield was 35% (GS -first), 26% (GS as a secondary test), and 11% (CMA/FMR1). Notably, the age of diagnosis was delayed by 1 year when GS was performed as a secondary test and the cost per diagnosed individual was 36% lower with GS first than with CMA/FMR1. Furthermore, 91% of those with a negative result after CMA/FMR1 analysis (338 individuals) have not yet been referred for additional genetic testing and remain undiagnosed. Conclusion: Our findings strongly suggest that genome analysis outperforms other testing strategies and should replace traditional CMA and FMR1 analysis as a first-line genetic test in individuals with ID/NDD. GS is a sensitive, time-and cost-effective method that results in a confirmed molecular diagnosis in 35% of all referred patients. (c) 2022 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY license (http://***/licenses/by/4.0/).

关键词： Chromosomal microarray Clinical diagnostics FMR1 analysis Genome sequencing Intellectual disability

来源：评论

学校读者我要写书评

暂无评论

Increasing involvement of CAPN1 variants in spastic ataxias and phenotype-genotype correlations

引用

NEUROGENETICS 2021年第1期22卷 71-79页

作者： Mereaux, Jean-Loup Firanescu, Cristina Coarelli, Giulia kvarnung, malin Rodrigues, Rita Pegoraro, Elena Tazir, Meriem Taithe, Frederic Valter, Remi Huin, Vincent Lidstrom, Kristina Banneau, Guillaume Morais, Sara Parodi, Livia Coutelier, Marie Papin, Melanie Svenningsson, Per Azulay, Jean-Philippe Alonso, Isabel Nilsson, Daniel Brice, Alexis Le Guern, Eric Press, Rayomand Vazza, Giovanni Loureiro, Jose Leal Goizet, Cyril Durr, Alexandra Paucar, Martin Stevanin, Giovanni Sorbonne Univ Paris Brain Inst Hop Pitie Salpetriere Inst CerveauICMInsermCNRSAP HPDMU Neurosci 6 Paris France Rouen Univ Hosp Rouen France Paris Sci & Lettres Univ EPHE Paris France Karolinska Univ Hosp Dept Neurol Stockholm Sweden Pitie Salpetriere Univ Hosp AP HP Natl Reference Ctr Rare Dis Neurogenet Dept Genet Paris France Karolinska Univ Hosp Dept Clin Genet Stockholm Sweden Karolinska Inst Ctr Mol Med Dept Mol Med & Surg Stockholm Sweden Ctr Hosp Entre Douro & Vouga Neurol Dept Santa Maria Feira Portugal Univ Padua ERN Neuromuscular Ctr Dept Neurosci DNS Padua Italy Univ Alger 1 CHU Mustapha Serv Neurol Lab Rech Neurosci Pl 1er Mai Algiers 16000 Algeria CHU Clermont Ferrand F-63000 Clermont Ferrand France Pitie Salpetriere Univ Hosp AP HP Dept Genet Paris France Univ Porto i3S Inst Invest & Inovacao Saude IBMC Inst Mol & Cell Biol UnIGENe Porto Portugal Univ Padua Dept Biol Padua Italy Karolinska Inst Dept Clin Neurosci Stockholm Sweden AMU Aix Marseille CNRS Dept Neurol & Pathol Mouvement Pole Neurosci ClinINT Marseille France Genetyca ICM Porto Portugal Bordeaux Univ Hosp Pellegrin Hosp Dept Med Genet Natl Reference Ctr Rare Dis Neurogenet Bordeaux France Bordeaux Univ INSERM U1211 Rare Dis Lab Genet & Metab MRGM Bordeaux France Hop La Pitie Salpetriere Inst Cerveau ICM CS21414 47 Bd Hop F-75646 Paris France

Spastic ataxias are rare neurogenetic disorders involving spinocerebellar and pyramidal tracts. Many genes are involved. Among them, CAPN1, when mutated, is responsible for a complex inherited form of spastic paraplegia (SPG76). We report the largest published series of 21 novel patients with nine new CAPN1 disease-causing variants and their clinical characteristics from two European university hospitals (Paris and Stockholm). After a formal clinical examination, causative variants were identified by next-generation sequencing and confirmed by Sanger sequencing. CAPN1 variants are a rare cause (similar to 1.4%) of young-adult-onset spastic ataxia;however, together with all published cases, they allowed us to better describe the clinical and genetic spectra of this form. Truncating variants are the most frequent, and missense variants lead to earlier age at onset in favor of an additional deleterious effect. Cerebellar ataxia with cerebellar atrophy, dysarthria and lower limb weakness are often associated with spasticity. We also suggest that cognitive impairment and depression should be assessed specifically in the follow-up of SPG76 cases.

关键词： CAPN1 Spastic ataxia Neurodegeneration Spastic paraplegia Cerebellar ataxia

来源：评论

学校读者我要写书评

暂无评论

Genome sequencing in a cohort of 32 fetuses with genetic skeletal disorders

引用

European journal of human genetics : EJHG 2025年 2025 Jun 11页

作者： Hillevi Lindelöf Anna Hammarsjö Ulrika Voss Serena Gaetana Piticchio Peter Conner Nikos Papadogiannakis Dominyka Batkovskyte Laura Orellana malin kvarnung Helena Malmgren Kristina Lagerstedt Robinson Ann Nordgren Anna Lindstrand Gen Nishimura Giedre Grigelioniene Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden. Department of Clinical Genetics and Genomics Karolinska University Hospital Stockholm Sweden. Department of Pediatric Radiology Karolinska University Hospital Stockholm Sweden. Protein Dynamics and Mutation lab Department of Oncology-Pathology Karolinska Institutet Stockholm Sweden. Center for Fetal Medicine Karolinska University Hospital Stockholm Sweden. Department of Laboratory Medicine Division of Pathology Karolinska Institutet Stockholm Sweden. Department of Radiology Musashino-Yowakai Hospital Tokyo Japan. Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden. giedre.grigelioniene@ki.se. Department of Clinical Genetics and Genomics Karolinska University Hospital Stockholm Sweden. giedre.grigelioniene@ki.se.

Approximately 200 genetic skeletal disorders can present prenatally, detectable through ultrasound abnormalities during pregnancy. Severe forms are typically identified during the first or second trimester, whereas milder phenotypes are recognized later, in the third trimester. Diagnosing skeletal dysplasia prenatally is challenging due to the large number of disorders and the overlapping clinical findings that can be detected by ultrasound. This study, conducted at Karolinska University Hospital between 2015 and 2022, examines the genetic and radiographic findings in 32 fetuses (14 female and 18 male, from unrelated families) with skeletal abnormalities detected on prenatal ultrasound and confirmed by radiographs at birth or after pregnancy termination. Fetal DNA samples from all 32 fetuses underwent singleton genome sequencing using an in silico skeletal dysplasia gene panel. As a second step, for six fetuses with molecularly unsolved diagnoses, trio genome sequencing analysis involving the fetus and both parents was performed. The diagnostic yield of genome sequencing was 72%, with pathogenic or likely pathogenic variants identified in 23 of the 32 fetuses. Additionally, four variants of uncertain significance, strongly suspected to be causative based on clinical and radiographic features, as well as structural protein analyses, were identified in four fetuses with autosomal recessive conditions. The diagnoses of five fetuses remain molecularly unsolved. In conclusion, by combining detailed phenotypic data with singleton genome sequencing we were able to reach a genetic diagnosis in 72% of 32 fetal genetic skeletal disorder cases investigated at the Karolinska University Hospital.

关键词：

来源：评论

学校读者我要写书评

暂无评论

TUBB3 Arg262His causes a recognizable syndrome including CFEOM3, facial palsy, joint contractures, and early-onset peripheral neuropathy

引用

HUMAN GENETICS 2021年第12期140卷 1709-1731页

作者： Whitman, Mary C. Barry, Brenda J. Robson, Caroline D. Facio, Flavia M. Van Ryzin, Carol Chan, Wai-Man Lehky, Tanya J. Thurm, Audrey Zalewski, Christopher King, Kelly A. Brewer, Carmen Almpani, Konstantinia Lee, Janice S. Delaney, Angela FitzGibbon, Edmond J. Lee, Paul R. Toro, Camilo Paul, Scott M. Abdul-Rahman, Omar A. Webb, Bryn D. Jabs, Ethylin Wang Moller, Hans Ulrik Larsen, Dorte Ancher Antony, Jayne H. Troedson, Christopher Ma, Alan Ragnhild, Glad Wirgenes, Katrine, V Tham, Emma kvarnung, malin Maarup, Timothy James MacKinnon, Sarah Hunter, David G. Collins, Francis S. Manoli, Irini Engle, Elizabeth C. Boston Childrens Hosp Dept Ophthalmol Boston MA 02115 USA Harvard Med Sch Dept Ophthalmol Boston MA 02115 USA Boston Childrens Hosp Dept Neurol Boston MA 02115 USA Howard Hughes Med Inst Chevy Chase MD 20815 USA Boston Childrens Hosp Dept Radiol Boston MA 02115 USA Harvard Med Sch Dept Radiol Boston MA 02115 USA NHGRI Ctr Precis Hlth Res NIH Bethesda MD 20892 USA NINDS EMG Sect NIH Bethesda MD 20892 USA NIMH Neurodev & Behav Phenotyping Serv NIH Bethesda MD 20892 USA NIDCD Audiol Unit Otolaryngol Branch NIH Bethesda MD 20892 USA Natl Inst Dent & Craniofacial Res NIH Bethesda MD 20892 USA Univ Wisconsin Dept Pediat Div Genet & Metab Madison WI USA Eunice Kennedy Shriver Natl Inst Child Hlth & Hum Pediat Endocrinol & Metab NIH Bethesda MD 20892 USA NEI Lab Sensorimotor Res NIH Bethesda MD 20892 USA NHGRI Undiagnosed Dis Program NIH Bethesda MD 20892 USA NIH Dept Rehabil Med Ctr Clin Bethesda MD 20892 USA JHU Sch Med Dept Biomed Engn Baltimore MD 21205 USA JHU Sch Med Dept Phys Med & Rehabil Baltimore MD 21205 USA Univ Mississippi Div Med Genet Med Ctr Jackson MS 39216 USA Icahn Sch Med Mt Sinai Dept Genet & Genom Sci New York NY 10029 USA Icahn Sch Med Mt Sinai Dept Cell Dev & Regenerat Biol New York NY 10029 USA Icahn Sch Med Mt Sinai Dept Pediat New York NY 10029 USA Aarhus Univ Aarhus Denmark Childrens Hosp Westmead Westmead NSW Australia Univ Sydney Specialty Genom Med Sydney NSW Australia Univ Hosp North Norway Dept Med Genet Tromso Norway Oslo Univ Hosp Dept Med Genet Oslo Norway Univ Oslo Inst Clin Med Oslo Norway Karolinska Univ Hosp Clin Genet Stockholm Sweden Karolinska Inst Dept Mol Med & Surg Stockholm Sweden Karolinska Univ Hosp Dept Clin Genet Stockholm Sweden Kaiser Permanente Dept Genet Los Angeles CA USA NIH Off Director Bethesda MD 20892 USA Boston Childrens Hosp Kirby Ctr Boston MA 02115 USA Harvard Med Sch Dept Neurol Boston MA 02115 USA St Jude Childrens Res Hosp 332 N Lauderdale

Microtubules are formed from heterodimers of alpha- and beta-tubulin, each of which has multiple isoforms encoded by separate genes. Pathogenic missense variants in multiple different tubulin isoforms cause brain malformations. Missense mutations in TUBB3, which encodes the neuron-specific beta-tubulin isotype, can cause congenital fibrosis of the extraocular muscles type 3 (CFEOM3) and/or malformations of cortical development, with distinct genotype-phenotype correlations. Here, we report fourteen individuals from thirteen unrelated families, each of whom harbors the identical NM_006086.4 (TUBB3):c.785G>A (***262His) variant resulting in a phenotype we refer to as the TUBB3 R262H syndrome. The affected individuals present at birth with ptosis, ophthalmoplegia, exotropia, facial weakness, facial dysmorphisms, and, in most cases, distal congenital joint contractures, and subsequently develop intellectual disabilities, gait disorders with proximal joint contractures, Kallmann syndrome (hypogonadotropic hypogonadism and anosmia), and a progressive peripheral neuropathy during the first decade of life. Subsets may also have vocal cord paralysis, auditory dysfunction, cyclic vomiting, and/or tachycardia at rest. All fourteen subjects share a recognizable set of brain malformations, including hypoplasia of the corpus callosum and anterior commissure, basal ganglia malformations, absent olfactory bulbs and sulci, and subtle cerebellar malformations. While similar, individuals with the TUBB3 R262H syndrome can be distinguished from individuals with the TUBB3 E410K syndrome by the presence of congenital and acquired joint contractures, an earlier onset peripheral neuropathy, impaired gait, and basal ganglia malformations.

关键词： Human Genetics Molecular Medicine Gene Function Metabolic Diseases

来源：评论

学校读者我要写书评

暂无评论

Genomic screening in rare disorders: New mutations and phenotypes, highlighting ALG14 as a novel cause of severe intellectual disability

引用

CLINICAL GENETICS 2018年第6期94卷 528-537页

作者： kvarnung, malin Taylan, Fulya Nilsson, Daniel Anderlid, Britt-Marie Malmgren, Helena Lagerstedt-Robinson, Kristina Holmberg, Eva Burstedt, Magnus Nordenskjoeld, Magnus Nordgren, Ann Lundberg, Elisabeth S. Karolinska Inst Dept Mol Med & Surg Ctr Mol Med Stockholm Sweden Karolinska Univ Hosp Dept Clin Genet L5 03 S-17176 Stockholm Sweden Karolinska Inst Sci Pk Sci Life Lab Stockholm Sweden Umea Univ Dept Med Biosci Med & Clin Genet Umea Sweden

We have investigated 20 consanguineous families with multiple children affected by rare disorders. Detailed clinical examinations, exome sequencing of affected as well as unaffected family members and further validation of likely pathogenic variants were performed. In 16/20 families, we identified pathogenic variants in autosomal recessive disease genes (ALMS1, PIGT, FLVCR2, TFG, CYP7B1, ALG14, EXOSC3, MEGF10, ASAH1, WDR62, ASPM, PNPO, ERCC5, KIAA1109, RIPK4, MAN1B1). A number of these genes have only rarely been reported previously and our findings thus confirm them as disease genes, further delineate the associated phenotypes and expand the mutation spectrum with reports of novel variants. We highlight the findings in two affected siblings with splice altering variants in ALG14 and propose a new clinical entity, which includes severe intellectual disability, epilepsy, behavioral problems and mild dysmorphic features, caused by biallelic variants in ALG14.

关键词： ALG14 exome sequencing genome screening intellectual disability KIAA1109 rare disorders

来源：评论

学校读者我要写书评

暂无评论

Pushing the boundaries of rare disease diagnostics with the help of the first Undiagnosed Hackathon

引用

NATURE GENETICS 2024年第11期56卷 2287-2294页

作者： Delgado-Vega, Angelica Maria Cederroth, Helene Taylan, Fulya Ekholm, Katja Ek, Marlene Thonberg, Hakan Jemt, Anders Nilsson, Daniel Eisfeldt, Jesper Saether, Kristine Bilgrav Hoijer, Ida Akgun-Dogan, Ozlem Asano, Yui Barakat, Tahsin Stefan Batkovskyte, Dominyka Baynam, Gareth Bodamer, Olaf Chetruengchai, Wanna Corcoran, Padraic Couse, Madeline Danis, Daniel Demidov, German Dohi, Eisuke Erhardsson, Mattias Fernandez-Luna, Luis Fujiwara, Toyofumi Garg, Neha Giugliani, Roberto Gonzaga-Jauregui, Claudia Grigelioniene, Giedre Groza, Tudor Gunnarsson, Cecilia Hammarsjo, Anna Hammond, Charles Kumi Ng, Ozden Hatirnaz Hesketh, Sirisha Hettiarachchi, Dineshani Soller, Maria Johansson Kirmani, Umn Ahmed Kjellberg, Martin kvarnung, malin Kvlividze, Oleg Lagerstedt-Robinson, Kristina Lasko, Paul Lassmann, Timo Lau, Lynette Y. S. Laurie, Steven Lim, Weng Khong Liu, Zhandong Wiklander, Mariya Lysenkova Makay, Prince Maiga, Alassane Baneye Maya-Gonzalez, Carolina Meyn, M. Stephen Neethiraj, Ramprasad Nigro, Vincenzo Nordgren, Felix Nordlund, Jessica Orrsjo, Sara Ottosson, Jesper Ozbek, Ugur Ozdemir, Ozkan Partin, Clyde Pearce, David A. Peck, Raquel Pedersen, Annie Pettersson, Maria Pongpanich, Monnat de la Paz, Manuel Posada Ramani, Arun Romero, Juan Andres Romero, Vanessa I. Rosenquist, Richard Saw, Aung Min Spencer, Matthew Stattin, Eva-Lena Srichomthong, Chalurmpon Tapia-Paez, Isabel Taruscio, Domenica Taylor, Julie P. Tkemaladze, Tinatin Tully, Ian Tumer, Zeynep van Zelst-Stams, Wendy A. G. Verloes, Alain Vasterviga, Emma Wang, Sailan Yang, Rachel Yamamoto, Shinya Yepez, Vicente A. Zhang, Qing Shotelersuk, Vorasuk Wiafe, Samuel Agyei Alanay, Yasemin Botto, Lorenzo D. Kirmani, Salman Lumaka, Aime Palmer, Elizabeth Emma Puri, Ratna Dua Wirta, Valtteri Lindstrand, Anna Buske, Orion J. Cederroth, Mikk Nordgren, Ann Karolinska Univ Hosp Dept Clin Genet & Genom Stockholm Sweden Karolinska Inst Dept Mol Med & Surg Stockholm Sweden Wilhelm Fdn Brottby Sweden Karolinska Inst Dept Microbiol Tumor & Cell Biol Sci Life Lab Stockholm Sweden Karolinska Univ Hosp Genom Med Ctr Karolinska Stockholm Sweden Karolinska Inst Dept Mol Med & Surg Sci Life Lab Stockholm Sweden Uppsala Univ Dept Immunol Genet & Pathol Uppsala Sweden Uppsala Univ Sci Life Lab Uppsala Sweden Acibadem Univ Sch Med Div Pediat Genet Dept Pediat Istanbul Turkiye Acibadem Univ Rare Dis & Orphan Drugs Applicat & Res Ctr ACURARE Istanbul Turkiye Acibadem Univ Dept Med Genet Istanbul Turkiye Swallow Design Studio Tokyo Japan Erasmus MC Univ Med Ctr Dept Clin Genet Rotterdam Netherlands Erasmus MC Univ Med Ctr Dept Clin Genet Discovery Unit Rotterdam Netherlands Erasmus MC ENCORE Expertise Ctr Neurodev Disorders Rotterdam Netherlands Perth Childrens Hosp Rare Care Ctr Perth WA Australia Western Australian Register Dev Anomalies Perth WA Australia King Edward Mem Hosp Undiagnosed Dis Program Genet Hlth WA Perth WA Australia Australian Natl Univ Fac Med Perth WA Australia Boston Childrens Hosp Dept Pediat Div Genet & Gen Boston MA USA Chulalongkorn Univ Fac Med Ctr Excellence Med Gen Dept Pediat Bangkok Thailand King Chulalongkorn Mem Hosp Thai Red Cross Soc Excellence Ctr Genom & Precis Med Bangkok Thailand Hosp Sick Children Ctr Computat Med Toronto ON Canada Jackson Lab Genom Med Farmington CT USA Univ Tubingen Inst Med Genet & Appl Gen Tubingen Germany Nat Inst Neurosci Natl Ctr Neurol & Psychiat Tokyo Japan Univ Gothenburg Sahlgrenska Acad Inst Biomed Dept Med Biochem & Cell Biol Gothenburg Sweden Univ Nacl Autonoma Mexico Int Lab Human Genome Res Lab Int Invest Genoma Humano Queretaro Mexico Res Org Informat & Syst Database Ctr Life Sci Joint Support Ctr Data Chiba Japan Sir Ganga Ram Hosp Inst Med Genet & Gen New Delhi India Casa dos Raros Porto Alegre RS Br

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：