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intellectual disease genetics

Dorothy A Fink, Lawrence M Nelson, Reed Pyeritz, Josh Johnson, Stephanie L Sherman, Yoram Cohen, Shai E Elizur
Abnormalities in the X-linked FMR1 gene are associated with a constellation of disorders, which have broad and profound implications for the person first diagnosed, and extended family members of all ages. The rare and pleiotropic nature of the associated disorders, both common and not, place great burdens on (1) the affected families, (2) their care providers and clinicians, and (3) investigators striving to conduct research on the conditions. Fragile X syndrome, occurring more severely in males, is the leading genetic cause of intellectual disability...
2018: Frontiers in Genetics
Allison M Matthews, Ingrid Blydt-Hansen, Basmah Al-Jabri, John Andersen, Maja Tarailo-Graovac, Magda Price, Katherine Selby, Michelle Demos, Mary Connolly, Britt Drögemoller, Casper Shyr, Jill Mwenifumbo, Alison M Elliott, Jessica Lee, Aisha Ghani, Sylvia Stöckler, Ramona Salvarinova, Hilary Vallance, Graham Sinclair, Colin J Ross, Wyeth W Wasserman, Margaret L McKinnon, Gabriella A Horvath, Helly Goez, Clara D van Karnebeek
PURPOSE: The presentation and etiology of cerebral palsy (CP) are heterogeneous. Diagnostic evaluation can be a prolonged and expensive process that might remain inconclusive. This study aimed to determine the diagnostic yield and impact on management of next-generation sequencing (NGS) in 50 individuals with atypical CP (ACP). METHODS: Patient eligibility criteria included impaired motor function with onset at birth or within the first year of life, and one or more of the following: severe intellectual disability, progressive neurological deterioration, other abnormalities on neurological examination, multiorgan disease, congenital anomalies outside of the central nervous system, an abnormal neurotransmitter profile, family history, brain imaging findings not typical for cerebral palsy...
December 13, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
Meenal Garg, Shilpa D Kulkarni, Anaita Udwadia Hegde, Margi Desai, Rafat J Sayed
Introduction: Giant axonal neuropathy (GAN) is an inherited neurodegenerative disorder caused by mutations in the GAN gene. It affects both the central and peripheral nervous systems. We discuss clinical, electrophysiological, radiological and genetic features in three new unrelated patients with GAN. Methods: Three pediatric patients with suspected GAN were included. The diagnosis was considered in patients with early onset polyneuropathy and characteristic hair with central nervous system involvement or suggestive neuroimaging findings...
October 2018: Annals of Indian Academy of Neurology
Teresa H Wen, Jonathan W Lovelace, Iryna M Ethell, Devin K Binder, Khaleel A Razak
Fragile X Syndrome (FXS) is a leading genetic cause of autism and intellectual disabilities. Sensory processing deficits are common in humans with FXS and an animal model, the Fmr1 knockout (KO) mouse, manifesting in the auditory system as debilitating hypersensitivity and abnormal electroencephalographic (EEG) and event-related potential (ERP) phenotypes. FXS is a neurodevelopmental disorder, but how EEG/ERP phenotypes change during development is unclear. Therefore, we characterized baseline and stimulus-evoked EEG in auditory and frontal cortex of developing (postnatal day (P) 21 and P30) and adult (P60) wildtype (WT) and Fmr1 KO mice with the FVB genetic background...
December 4, 2018: Neuroscience
Joshi Stephen, Sateesh Maddirevula, Sheela Nampoothiri, John D Burke, Matthew Herzog, Anju Shukla, Katharina Steindl, Ascia Eskin, Siddaramappa J Patil, Pascal Joset, Hane Lee, Lisa J Garrett, Tadafumi Yokoyama, Nicholas Balanda, Steven P Bodine, Nathanial J Tolman, Patricia M Zerfas, Allison Zheng, Georgia Ramantani, Katta M Girisha, Cecilia Rivas, Pujar V Suresh, Abdel Elkahloun, Hessa S Alsaif, Salma M Wakil, Laila Mahmoud, Rehab Ali, Michaela Prochazkova, Ashok B Kulkarni, Tawfeg Ben-Omran, Dilek Colak, H Douglas Morris, Anita Rauch, Julian A Martinez-Agosto, Stanley F Nelson, Fowzan S Alkuraya, William A Gahl, May Christine V Malicdan
Neurodevelopmental disorders (NDD) are genetically and phenotypically heterogeneous conditions due to defects in genes involved in development and function of the nervous system. Individuals with NDD, in addition to their primary neurodevelopmental phenotype, may also have accompanying syndromic features that can be very helpful diagnostically especially those with recognizable facial appearance. In this study, we describe ten similarly affected individuals from six unrelated families of different ethnic origins having bi-allelic truncating variants in TMEM94, which encodes for an uncharacterized transmembrane nuclear protein that is highly conserved across mammals...
December 6, 2018: American Journal of Human Genetics
Miriam Kessi, Juan Xiong, Liwen Wu, Lifen Yang, Fang He, Chen Chen, Nan Pang, Haolin Duan, Wen Zhang, Ahmed Arafat, Fei Yin, Jing Peng
Introduction: The concurrence of intellectual disability/global developmental delay and epilepsy (ID/GDD-EP) is very common in the pediatric population. The etiologies for both conditions are complex and largely unknown. The predictors of significant copy number variations (CNVs) are known for the cases with ID/GDD, but unknown for those with exclusive ID/GDD-EP. Importantly, the known predictors are largely from the same ethnic group; hence, they lack replication. Purpose: We aimed to determine and investigate the diagnostic yield of CNV tests, new causative CNVs, and the independent predictors of significant CNVs in Chinese children with unexplained ID/GDD-EP...
2018: Frontiers in Neurology
Dang Ton Nguyen, Hai Ha Nguyen, Thuy Duong Nguyen, Thi Thanh Hoa Nguyen, Kaoru Nakano, Kazuhiro Maejima, Aya Sasaki-Oku, Van Ba Nguyen, Duy Bac Nguyen, Bach Quang Le, Jing Hao Wong, Tatsuhiko Tsunoda, Hidewaki Nakagawa, Akihiro Fujimoto, Van Hai Nong
Although it has been a half-century since dioxin-contaminated herbicides were used to defoliate the landscape during the Vietnam War, dioxin contamination "hotspots" still remain in Vietnam. Environmental and health impacts of these hotspots need to be evaluated. Intellectual disability (ID) is one of the diseases found in the children of people exposed to the herbicides. This study aims to identify genetic alterations of a patient whose family lived in a dioxin hotspot. The patient's father had a highly elevated dioxin concentration...
November 23, 2018: International Journal of Environmental Research and Public Health
İlker Karacan, Reyhan Diz Küçükkaya, Fatma Nur Karakuş, Seyhun Solakoğlu, Aslıhan Tolun, Veysel Sabri Hançer, Eda Tahir Turanlı
OBJECTIVE: Autosomal recessive cutis laxa type IIA (ARCL2A) is a rare congenital disorder characterized by loose and elastic skin, growth and developmental delay, and skeletal anomalies. It is caused by biallelic mutations in ATP6V0A2 . Those mutations lead to increased pH in secretory vesicles and thereby to impaired glycosyltransferase activity and organelle trafficking. We aimed to identify the genetic and molecular cause of the unexpected haematological findings in a Turkish family...
November 26, 2018: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
D V Bryzgalov, I L Kuznetsova, E I Rogaev
The problem of memory enhancement is extremely important in intellectual activity areas and therapy of different types of dementia, including Alzheimer's disease (AD). The attempts to solve this problem have come from different research fields. In the first part of our review, we describe the results of targeting certain genes involved in memory-associated molecular pathways. The second part of the review is focused on the deep stimulation of brain structures that can slow down memory loss in AD. The third part describes the results of the use of non-invasive brain stimulation techniques for memory modulation, consolidation, and retrieval in healthy people and animal models...
September 2018: Biochemistry. Biokhimii︠a︡
Leda Paganini, Loubna Abdel Hadi, Massimiliano Chetta, Davide Rovina, Laura Fontana, Patrizia Colapietro, Eleonora Bonaparte, Lidia Pezzani, Paola Marchisio, Tabano Silvia Maria, Jole Costanza, Sirchia Silvia Maria, Laura Riboni, Donatella Milani, Monica Miozzo
X-Linked Intellectual Disability (XLID) refers to a clinically and genetically heterogeneous neurodevelopmental disorder, in which males are more heavily affected than females. Among the syndromic forms of XLID, identified by additional clinical signs as part of the disease spectrum, the association between XLID and severe myopia has been poorly characterized. We used Whole Exome Sequencing (WES) to study two Italian male twins presenting impaired intellectual function and adaptive behavior, in association with severe myopia and mild facial dysmorphisms...
November 24, 2018: Clinical Genetics
Yanyan Qian, Bingbing Wu, Yulan Lu, Xinran Dong, Qian Qin, Wenhao Zhou, Huijun Wang
Epileptic encephalopathies are severe seizure disorders accompanied by intellectual disability. Whole-exome sequencing technology has enabled the discovery of genetic mutations responsible for a wide range of diseases, and severe epilepsy and neurodevelopmental diseases are often associated with rare de novo mutations. We identified a novel de novo frameshift mutation in the PPP3CA gene encoding calcium-dependent protein phosphatase (calcineurin) catalytic subunit A (c.1255_1256del, p.Ser419Cysfs*31) in an 11...
November 19, 2018: Cold Spring Harbor Molecular Case Studies
Pengzhi Hu, Lamei Yuan, Hao Deng
Protein O-mannosyltransferase 1 (POMT1) is a critical enzyme participating in the first step of protein O-mannosylation. Mutations in the coding gene, POMT1, have been described to be related to a series of autosomal recessive disorders associated with defective alpha-dystroglycan glycosylation, later termed muscular dystrophy-dystroglycanopathies (MDDGs). MDDGs are characterized by a broad phenotypic spectrum of congenital muscular dystrophy or later-onset limb-girdle muscular dystrophy, accompanied by variable degrees of intellectual disability, brain defects, and ocular abnormalities...
October 2018: Mutation Research
Cecilia Mancini, Andrea Zonta, Giovanni Botta, Andrea Breda Klobus, Stefano Valbonesi, Barbara Pasini, Elisa Giorgio, Elsa Viora, Alfredo Brusco, Alessandro Brussino
Microphthalmia with limb anomalies (MLA, OMIM, 206920) is a rare autosomal-recessive disease caused by biallelic pathogenic variants in the SMOC1 gene. It is characterized by ocular disorders (microphtalmia or anophtalmia) and limb anomalies (oligodactyly, syndactyly, and synostosis of the 4th and 5th metacarpals), variably associated with long bone hypoplasia, horseshoe kidney, venous anomalies, vertebral anomalies, developmental delay, and intellectual disability. Here, we report the case of a woman who interrupted her pregnancy after ultrasound scans revealed a depression of the frontal bone, posterior fossa anomalies, cerebral ventricular enlargement, cleft spine involving the sacral and lower-lumbar vertebrae, and bilateral microphthalmia...
November 13, 2018: European Journal of Medical Genetics
Z J Gao, Q Jiang, X L Chen, Q Chen, X N Ji, Y Y Mao, S Feng, J J Dong, K M Xu
Objective: To analyze the de novo point mutations in known genes among patients with unexplained intellectual disability (ID) or developmental retardation (DD). Methods: A total of 120 outpatients with ID or DD were recruited in the Department of Neurology, Affiliated Children's Hospital of Capital Institute of Pediatrics between September 2015 and April 2017. Target gene sequencing was used to screen the candidate gene. The sequencing data were analyzed by a variety of bioinformatics software. Combining with the phenotypes of the patients, the candidate genetic/genomic variants were identified from next-generation sequencing data...
November 13, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
M Elmas, H Yıldız, M Erdoğan, B Gogus, K Avcı, M Solak
Whole-exome sequencing (WES) is an ideal method for the diagnosis of autosomal recessive diseases. The aim of this study was to evaluate the diagnostic power of WES in patients with autosomal recessive inheritance and to determine the relationship between genotype and phenotype. Retrospective screenings of 24 patients analysed with WES were performed and clinical and genetic data were evaluated. Any pathogenic mutation that could explain the suspected disease in 4 patients was not identified. A homozygous pathogenic mutation was detected in 18 patients...
November 13, 2018: Molecular Biology Reports
Ye Zhu, Gautam Runwal, Pawel Obrocki, David C Rubinsztein
Autophagy is a tightly modulated lysosomal degradation pathway. Genetic disorders of autophagy during nervous system development may lead to developmental delay, neurodegeneration, and other neurological signs in children. Here we aimed to summarize single gene disorders that perturb various steps of autophagy pathway and their roles in the causation of childhood neurological diseases. Numerous childhood-onset disorders are caused by mutations that impact the autophagy pathway. These can manifest with a range of features including ataxia, spastic paraplegia, and intellectual disability...
November 12, 2018: Developmental Medicine and Child Neurology
Qin Wang, Jingxin Yang, Yang Liu, Xingping Li, Fuwei Luo, Jiansheng Xie
BACKGROUND: X-linked creatine transporter deficiency (OMIM#300036,CRTR-D) is characterized by cerebral creatine deficiency, intellectual disabilities, severe speech impairment, seizures and behavioral problems. Mutations in the creatine transporter gene SLC6A8, a member of the solute-carrier family 6 mapped to Xq28, have been reported to cause the creatine transporter deficiency. CASE PRESENTATION: The proband presented at 5 yrs. 1 month of age with delays in intellectual and development, seizures and behavioral problems...
November 6, 2018: BMC Medical Genetics
Demy J S Kuipers, Jonathan Carr, Soraya Bardien, Pearl Thomas, Boiketlo Sebate, Guido J Breedveld, Rick van Minkelen, Rutger W W Brouwer, Wilfred F J van Ijcken, Marjon A van Slegtenhorst, Vincenzo Bonifati, Marialuisa Quadri
BACKGROUND: The genetic bases of PD in sub-Saharan African (SSA) populations remain poorly characterized, and analysis of SSA families with PD might lead to the discovery of novel disease-related genes. OBJECTIVES: To investigate the clinical features and identify the disease-causing gene in a black South African family with 3 members affected by juvenile-onset parkinsonism and intellectual disability. METHODS: Clinical evaluation, neuroimaging studies, whole-exome sequencing, homozygosity mapping, two-point linkage analysis, and Sanger sequencing of candidate variants...
November 2018: Movement Disorders: Official Journal of the Movement Disorder Society
Karl P Schlingmann, Sascha Bandulik, Cherry Mammen, Maja Tarailo-Graovac, Rikke Holm, Matthias Baumann, Jens König, Jessica J Y Lee, Britt Drögemöller, Katrin Imminger, Bodo B Beck, Janine Altmüller, Holger Thiele, Siegfried Waldegger, William Van't Hoff, Robert Kleta, Richard Warth, Clara D M van Karnebeek, Bente Vilsen, Detlef Bockenhauer, Martin Konrad
Over the last decades, a growing spectrum of monogenic disorders of human magnesium homeostasis has been clinically characterized, and genetic studies in affected individuals have identified important molecular components of cellular and epithelial magnesium transport. Here, we describe three infants who are from non-consanguineous families and who presented with a disease phenotype consisting of generalized seizures in infancy, severe hypomagnesemia, and renal magnesium wasting. Seizures persisted despite magnesium supplementation and were associated with significant intellectual disability...
November 1, 2018: American Journal of Human Genetics
Gerarda Cappuccio, Annalaura Torella, Mario Mastrangelo, Claudia Carducci, Vincenzo Nigro, Nicola Brunetti-Pierri, Vincenzo Leuzzi
In 2012 Acta Paediatrica published our paper, which reported a possible new form of cerebral folate deficiency, with microcephaly, growth delay, severe intellectual disability and compulsive self-harm behaviour (1). Our patient has now been included in the Telethon Undiagnosed Diseases Program, which aims at providing diagnoses for paediatric patients with an unnamed genetic disease. This article is protected by copyright. All rights reserved.
November 1, 2018: Acta Paediatrica
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