GM03200

GM03200 LCL from B-Lymphocyte

Description:

FRAGILE X MENTAL RETARDATION SYNDROME
FMR1 GENE; FMR1

Affected:

Yes

Sex:

Male

Age:

34 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

White

Relation to Proband

proband

Confirmation

Karyotypic analysis after cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

46,fra(X)(q27),Y; 17% in PBL and 7 to 50% of lymphoblasts using FudR; negative for FMR-1 gene expression; affected male by Southern analysis

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

X CHROMOSOME FRAGILE SITE

Pieretti et al (Cell 66:817-822,1991) reported that there was no detectable expression of the gene, FMR-1, that is expressed in brain at the fragile X locus in this lymphoblast culture established from a male with fragile X syndrome.

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

46,fra(X)(q27),Y; 17% in PBL and 7 to 50% of lymphoblasts using FudR; negative for FMR-1 gene expression; affected male by Southern analysis

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: 2022

PubMed ID: 35394024

Joshi I, DeRycke J, Palmowski M, LeSuer R, Feng W, Genome-wide mapping of DNA double-strand breaks from eukaryotic cell cultures using Break-seq STAR protocols2:100554 2021

PubMed ID: 34189468

Chakraborty A, Jenjaroenpun P, Li J, El Hilali S, McCulley A, Haarer B, Hoffman EA, Belak A, Thorland A, Hehnly H, Schildkraut C, Chen CL, Kuznetsov VA, Feng W, Replication Stress Induces Global Chromosome Breakage in the Fragile X Genome Cell reports32:108179 2020

PubMed ID: 32966779

Kumari D, Sciascia N, Usdin K, Small Molecules Targeting H3K9 Methylation Prevent Silencing of Reactivated Genes11:108179 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

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 genetics105:151-165 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

Smith KT, Nicholls RD, Reines D, The gene encoding the fragile X RNA-binding protein is controlled by nuclear respiratory factor 2 and the CREB family of transcription factors Nucleic acids research34:1205-15 2006

PubMed ID: 16500891

Smith KT, Coffee B, Reines D, Occupancy and synergistic activation of the FMR1 promoter by Nrf-1 and Sp1 in vivo. Hum Mol Genet13(15):1611-21 2004

PubMed ID: 15175277

Coffee B, Zhang F, Ceman S, Warren ST, Reines D, Histone modifications depict an aberrantly heterochromatinized FMR1 gene in fragile x syndrome. Am J Hum Genet71(4):923-32 2002

PubMed ID: 12232854

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

Abruzzo MA, Hunt PA, Mayer M, Jacobs PA, Wang JC, Erbe RW, Cytogenetic analysis of lymphoblastoid cell lines. Cytogenet Cell Genet42:169-73 1986

PubMed ID: 3731885

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

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

Rattner JB, Lin CC, Radial loops and helical coils coexist in metaphase chromosomes. Cell42:291-6 1985

PubMed ID: 4016953

Howard-Peebles PN, Pryor JC, Marker X chromosomes and tissue-culture conditions [letter] N Engl J Med301:166 1979

PubMed ID: 36560

Howard-Peebles PN, Stoddard GR, Mims MG, Familial X-linked mental retardation, verbal disability, and marker X chromosomes. Am J Hum Genet31:214-22 1979

PubMed ID: 453204