Book ChapterDOI
X-linked mental deficiency.
Reads0
Chats0
TLDR
Although some forms of X-linked mental retardation are not very specific and the phenotype for each given gene is somewhat heterogeneous, a clinical diagnostic strategy is emerging.Abstract:
Ten percent of cases of intellectual deficiency in boys are caused by genes located on the X chromosome. X-linked mental retardation (XLMR) includes more than 200 syndromes and 80 genes identified to date. The fragile X syndrome is the most frequent syndrome, due to a dynamic mutation with a CGG triplet amplification. Mental retardation is virtually always present. Phonological and syntactic impairments are often combined with pragmatic language impairment and visuospatial reasoning difficulties. A minority fulfill the criteria for autism. In girls, the clinical expression of the complete mutation varies according to the X chromosome inactivation profile. Several XLMR occur as severe early onset encephalopathies: Lowe oculocerebrorenal syndrome, ATR-X syndrome (alpha thalassemia/mental retardation X-linked), Allan-Herdon-Dudley syndrome (MCT8 gene). Two genes, ARX (X-LAG; Partington syndrome) and MECP2 (Rett syndrome in females; mild MR with spastic diplegia/psychotic problems in males) are associated with various phenotypes, according to the mutation involved. Oligophrenine 1 (OPHN-1) gene mutations lead to vermal dysplasia. PQBP1 gene mutations (Renpenning syndrome) are responsible for moderate to severe mental deficiency, microcephaly, and small stature. Although some forms of XLMR are not very specific and the phenotype for each given gene is somewhat heterogeneous, a clinical diagnostic strategy is emerging.read more
Citations
More filters
Journal ArticleDOI
Distinct and overlapping functions of the cullin E3 ligase scaffolding proteins CUL4A and CUL4B
Jeffrey Hannah,Pengbo Zhou +1 more
TL;DR: The most essential functions of the CUL4 genes in: DNA repair and replication, chromatin-remodeling, cell cycle regulation, embryogenesis, hematopoiesis and spermatogenesis are highlighted.
Journal ArticleDOI
Variants in HNRNPH2 on the X Chromosome Are Associated with a Neurodevelopmental Disorder in Females
Jennifer M. Bain,Megan T. Cho,Aida Telegrafi,Ashley Wilson,Susan Sklower Brooks,Christina Botti,Gordon C. Gowans,Leigh Anne Autullo,Vidya Krishnamurthy,Marcia C. Willing,Tomi L. Toler,Bruria Ben-Zev,Orly Elpeleg,Yufeng Shen,Kyle Retterer,Kristin G. Monaghan,Wendy K. Chung +16 more
TL;DR: Six females from independent families with a common neurodevelopmental phenotype including developmental delay, intellectual disability, autism, hypotonia, and seizures are identified with de novo predicted deleterious variants in the nuclear localization signal of Heterogeneous Nuclear Ribonucleoprotein H2, encoded by HNRNPH2, a gene located on the X chromosome.
Journal ArticleDOI
Placebo Responses in Genetically Determined Intellectual Disability: A Meta-Analysis.
Aurore Curie,Katherine Yang,Irving Kirsch,Irving Kirsch,Randy L. Gollub,Vincent des Portes,Ted J. Kaptchuk,Karin B. Jensen,Karin B. Jensen,Karin B. Jensen +9 more
TL;DR: The results suggest that patients with genetically determined ID improve in the placebo arm of RCTs, demonstrating how contextual factors can affect clinical outcomes and emphasize the importance of being vigilant on the role of placebos when testing novel treatments in ID.
Journal ArticleDOI
Reconsidering animal models used to study autism spectrum disorder: Current state and optimizing future
Jill L. Silverman,Audrey Thurm,Sarah B Ethridge,Makayla M Soller,Stela P. Petkova,Ted Abel,Melissa D. Bauman,Edward S. Brodkin,Hala Harony-Nicolas,Markus Wöhr,Alycia K. Halladay +10 more
TL;DR: In this paper , the authors discuss the maximal utility and limitations of behavior in animal models with construct validity and provide guidelines on how in vivo models should be used and reported reliably and rigorously.
Journal ArticleDOI
Insights into the Genetic Foundations of Human Communication
TL;DR: Evidence from genetics, molecular cell biology, animal models and human neuroimaging has converged to build a picture of the role of FOXP2 in neurodevelopment, providing a framework for future endeavors to bridge the gaps between genes, brains and behavior.
References
More filters
Journal ArticleDOI
The mGluR theory of fragile X mental retardation
TL;DR: Loss of fragile X mental retardation protein (FMRP), the defect responsible for fragile X syndrome in humans, increases LTD in mouse hippocampus, consistent with the growing evidence that FMRP normally functions as a repressor of translation of specific mRNAs.
Journal ArticleDOI
Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome
I. Oberlé,François Rousseau,Dominique Heitz,Christine Kretz,Didier Devys,André Hanauer,Joëlle Boué,Bertheas Mf,Jean-Louis Mandel +8 more
TL;DR: expression of the fragile X syndrome appears to result from a two-step mutation as well as a highly localized methylation, and can easily be detected regardless of sex or phenotypic expression.
Journal ArticleDOI
Fragile X Premutation Tremor/Ataxia Syndrome: Molecular, Clinical, and Neuroimaging Correlates
Sébastien Jacquemont,Randi J Hagerman,Maureen A. Leehey,Jim Grigsby,Lin Zhang,James A. Brunberg,Claudia M. Greco,Vincent des Portes,Tristan Jardini,Richard A. Levine,Elizabeth Berry-Kravis,W. Ted Brown,Stephane Schaeffer,John T. Kissel,Flora Tassone,Paul J. Hagerman +15 more
TL;DR: The clinical presentation of these patients, coupled with a specific lesion visible on magnetic resonance imaging and with neuropathological findings, affords a more complete delineation of this fragile X premutation-associated tremor/ataxia syndrome and distinguishes it from other movement disorders.
Journal ArticleDOI
Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans.
Kunio Kitamura,Masako Yanazawa,Noriyuki Sugiyama,Hirohito Miura,Akiko Iizuka-Kogo,Masatomo Kusaka,Kayo Omichi,Rika Suzuki,Yuko Kato-Fukui,Kyoko Kamiirisa,Mina Matsuo,Shin Ichi Kamijo,Megumi Kasahara,Hidefumi Yoshioka,Tsutomu Ogata,Takayuki Fukuda,Ikuko Kondo,Mitsuhiro Kato,William B. Dobyns,Minesuke Yokoyama,Ken Ichirou Morohashi +20 more
TL;DR: The present report is the first to use phenotypic analysis of a knockout mouse to identify a gene associated with an X-linked human brain malformation, and concludes that mutation of ARX causes XLAG.
Journal ArticleDOI
A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene.
TL;DR: For the first time, mutations in the monocarboxylate transporter 8 (MCT8) gene, located on the X chromosome, have been linked to a defect in cellular hormone transport as mentioned in this paper.