GM04025

GM04025 LCL from B-Lymphocyte

Description:

FRAGILE X MENTAL RETARDATION SYNDROME
FMR1 GENE; FMR1

Affected:

Yes

Sex:

Male

Age:

29 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Chromosome Abnormalities

Class

Disorders with Trinucleotide Expansions

Class

X Chromosome Markers

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

Black/African American

Family Member

Relation to Proband

proband

Confirmation

Clinical summary/Case history

ISCN

46,XY[20]

Species

Homo sapiens

Common Name

Human

Remarks

Macro-orchidism; mental retardation; 52% 46,fra(X)(q27),Y in PBL and 4% in fibroblasts; fra(X) observed in 0 to 50% of lymphoblasts using FudR; G6PD type A in blood; see GM04024 Fibroblast; CGG repeat size of 645 in the FMR1 gene as detected by PCR (normal size range is 5-45 repeats); full mutation (fully methylated) characteristic of Fragile X syndrome.

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis and by Chromosome Analysis

Gene

FMR1

Chromosomal Location

Xq27.3

Allelic Variant 1

309550.0004; FRAGILE X MENTAL RETARDATION SYNDROME

Identified Mutation

(CGG)n EXPANSION; The usual cause of the fragile X syndrome is an expanded (CGG)n repeat in the 5-prime noncoding region of the FMR1 gene.

Phenotypic Data

Remarks

Publications

Caballero M, Ge T, Rebelo AR, Seo S, Kim S, Brooks K, Zuccaro M, Kanagaraj R, Vershkov D, Kim D, Smogorzewska A, Smolka M, Benvenisty N, West SC, Egli D, Mace EM, Koren A, Comprehensive analysis of DNA replication timing across 184 cell lines suggests a role for MCM10 in replication timing regulation Human molecular genetics: 2021

PubMed ID: 35394024

Dolskiy AA, Yarushkin AA, Grishchenko IV, Lemskaya NA, Pindyurin AV, Boldyreva LV, Pustylnyak VO, Yudkin DV, miRNA expression and interaction with the 3'UTR of FMR1 in FRAXopathy pathogenesis Non-coding RNA research6:1-7 2020

PubMed ID: 33426406

Kumari D, Sciascia N, Usdin K, Small Molecules Targeting H3K9 Methylation Prevent Silencing of Reactivated Genes11:1-7 2020

PubMed ID: 32230785

Kurosaki T, Imamachi N, Pröschel C, Mitsutomi S, Nagao R, Akimitsu N, Maquat LE, Loss of the fragile X syndrome protein FMRP results in misregulation of nonsense-mediated mRNA decay Nature cell biology23:40-48 2019

PubMed ID: 33420492

Rafehi H, Szmulewicz DJ, Bennett MF, Sobreira NLM, Pope K, Smith KR, Gillies G, Diakumis P, Dolzhenko E, Eberle MA, Barcina MG, Breen DP, Chancellor AM, Cremer PD, Delatycki MB, Fogel BL, Hackett A, Halmagyi GM, Kapetanovic S, Lang A, Mossman S, Mu W, Patrikios P, Perlman SL, Rosemergy I, Storey E, Watson SRD, Wilson MA, Zee DS, Valle D, Amor DJ, Bahlo M, Lockhart PJ, Bioinformatics-Based Identification of Expanded Repeats: A Non-reference Intronic Pentamer Expansion in RFC1 Causes CANVAS American journal of human genetics105:151-165 2019

PubMed ID: 31230722

Sun JH, Zhou L, Emerson DJ, Phyo SA, Titus KR, Gong W, Gilgenast TG, Beagan JA, Davidson BL, Tassone F, Phillips-Cremins JE, Disease-Associated Short Tandem Repeats Co-localize with Chromatin Domain Boundaries Cell175:224-238.e15 2018

PubMed ID: 30173918

Tankard RM, Bennett MF, Degorski P, Delatycki MB, Lockhart PJ, Bahlo M, Detecting Expansions of Tandem Repeats in Cohorts Sequenced with Short-Read Sequencing Data American journal of human genetics175:224-238.e15 2017

PubMed ID: 30503517

Kumari D, Swaroop M, Southall N, Huang W, Zheng W, Usdin K, High-Throughput Screening to Identify Compounds That Increase Fragile X Mental Retardation Protein Expression in Neural Stem Cells Differentiated From Fragile X Syndrome Patient-Derived Induced Pluripotent Stem Cells Stem cells translational medicine4:800-8 2014

PubMed ID: 25999519

Grasso M, Boon EM, Filipovic-Sadic S, van Bunderen PA, Gennaro E, Cao R, Latham GJ, Hadd AG, Coviello DA., A Novel Methylation PCR that Offers Standardized Determination of FMR1 Methylation and CGG Repeat Length without Southern Blot Analysis. J Mol Diagn.13:pii: S1525-1578 2013

PubMed ID: 24177047

Adler K, Moore JK, Filippov G, Wu S, Carmichael J, Schermer M, A novel assay for evaluating fragile x locus repeats The Journal of molecular diagnostics : JMD13:614-20 2011

PubMed ID: 21798368

Juusola JS, Anderson P, Sabato F, Wilkinson DS, Pandya A, Ferreira-Gonzalez A, Performance evaluation of two methods using commercially available reagents for PCR-based detection of FMR1 mutation The Journal of molecular diagnostics : JMD14:476-86 2011

PubMed ID: 22765921

Lyon E, Laver T, Yu P, Jama M, Young K, Zoccoli M, Marlowe N, A simple, high-throughput assay for Fragile X expanded alleles using triple repeat primed PCR and capillary electrophoresis The Journal of molecular diagnostics : JMD12:505-11 2010

PubMed ID: 20431035

Lavedan CN, Garrett L, Nussbaum RL, Trinucleotide repeats (CGG)22TGG(CGG)43TGG(CGG)21 from the fragile X gene remain stable in transgenic mice. Hum Genet100:407-14 1997

PubMed ID: 9272164

Maxwell IH, Glode LM, Maxwell F, Expression of the diphtheria toxin A-chain coding sequence under the control of promoters and enhancers from immunoglobulin genes as a means of directing toxicity to B-lymphoid cells. Cancer Res51:4299-304 1991

PubMed ID: 1868451

Pieretti M, Zhang FP, Fu YH, Warren ST, Oostra BA, Caskey CT, Nelson DL, Absence of expression of the FMR-1 gene in fragile X syndrome. Cell66:817-22 1991

PubMed ID: 1878973

Verkerk AJ, Pieretti M, Sutcliffe JS, Fu YH, Kuhl DP, Pizzuti A, Reiner O, Richards S, Victoria MF, Zhang FP, et al, Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell65:905-14 1991

PubMed ID: 1710175

Vincent A, Heitz D, Petit C, Kretz C, Oberle I, Mandel JL, Abnormal pattern detected in fragile-X patients by pulsed-field gel electrophoresis. Nature349:624-6 1991

PubMed ID: 1672039

Yu WD, Wenger SL, Steele MW, X chromosome imprinting in fragile X syndrome. Hum Genet85:590-4 1990

PubMed ID: 2227950

Ledbetter SA, Ledbetter DH, A common fragile site at Xq27: theoretical and practical implications. Am J Hum Genet42:694-702 1988

PubMed ID: 3358421

Trent JM, Flink IL, Morkin E, van Tuinen P, Ledbetter DH, Localization of the human thyroxine-binding globulin gene to the long arm of the X chromosome (Xq21-22). Am J Hum Genet41:428-35 1987

PubMed ID: 3115094

Ledbetter DH, Airhart SD, Nussbaum RL, Caffeine enhances fragile (X) expression in somatic cell hybrids. Am J Med Genet23:445-55 1986

PubMed ID: 2937299

Ledbetter DH, Airhart SD, Nussbaum RL, Somatic cell hybrid studies of fragile (X) expression in a carrier female and transmitting male. Am J Med Genet23:429-43 1986

PubMed ID: 2937298

Ledbetter DH, Ledbetter SA, Nussbaum RL, Implications of fragile X expression in normal males for the nature of the mutation. Nature324:161-3 1986

PubMed ID: 3785381

Maxwell IH, Maxwell F, Glode LM, Regulated expression of a diphtheria toxin A-chain gene transfected into human cells: possible strategy for inducing cancer cell suicide. Cancer Res46:4660-4 1986

PubMed ID: 3460697

Nussbaum RL, Airhart SD, Ledbetter DH, A rodent-human hybrid containing Xq24-qter translocated to a hamster chromosome expresses the Xq27 folate-sensitive fragile site. Am J Med Genet23:457-66 1986

PubMed ID: 2937300

Cantu ES, Nussbaum RL, Airhart SD, Ledbetter DH, Fragile (X) expression induced by FUdR is transient and inversely related to levels of thymidylate synthase activity. Am J Hum Genet37:947-55 1985

PubMed ID: 2931977

Howard-Peebles PN, Stoddard GR, Race distribution in X-linked mental retardation with macro-orchidism and fragile site in Xq [letter] Am J Hum Genet32:629-30 1980

PubMed ID: 6930822