A Case of Mosaicism with Fragile-X and XXY Components

1987 ◽  
Vol 150 (5) ◽  
pp. 700-702 ◽  
Author(s):  
Saumitra Deb ◽  
Valerie A. Cowie ◽  
Carol Timberlake
Keyword(s):  
Cell Lines ◽  
Fragile Site ◽  
Fragile X ◽  
Chromosomal Mosaicism ◽  
Mentally Handicapped ◽  
Phenotypic Features

The case of a 63-year-old severely mentally handicapped man is reported with chromosomal mosaicism. His karyotype was established as mosaic 46XY/47XXY with the fragile site present in a proportion of cells of both cell-lines. He showed phenotypic features which could be related both to the fragile-X and Klinefelter's syndromes.

scholarly journals Analysis of unstable DNA sequence in FMR1 gene in Polish families with fragile X syndrome.

1996 ◽  
Vol 43 (2) ◽  
pp. 383-388
Author(s):  
M Milewski ◽  
M Zygulska ◽  
J Bal ◽  
W H Deelen ◽  
E Obersztyn ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Dna Sequence ◽  
Clinical Features ◽  
Fragile Site ◽  
Fragile X ◽  
Fmr1 Gene ◽  
Repeat Number ◽  
Full Mutation ◽  
Cgg Repeats ◽  
Large Expansion

The unstable DNA sequence in the FMR1 gene was analyzed in 85 individuals from Polish families with fragile X syndrome in order to characterize mutations responsible for the disease in Poland. In all affected individuals classified on the basis of clinical features and expression of the fragile site at X(q27.3) a large expansion of the unstable sequence (full mutation) was detected. About 5% (2 of 43) of individuals with full mutation did not express the fragile site. Among normal alleles, ranging in size from 20 to 41 CGG repeats, allele with 29 repeats was the most frequent (37%). Transmission of premutated and fully mutated alleles to the offspring was always associated with size increase. No change in repeat number was found when normal alleles were transmitted.

FRAGILE X CHROMOSOME: CONSISTENT DEMONSTRATION OF FRAGILE SITE IN FIBROBLAST CULTURES

The Lancet ◽  
1982 ◽  
Vol 319 (8263) ◽  
pp. 101 ◽  
Author(s):  
AnneP. Gardner ◽  
R.T. Howell ◽  
A. Mcdermott
Keyword(s):  
X Chromosome ◽  
Fragile Site ◽  
Fragile X ◽  
Fibroblast Cultures

Fragile X: A Family of Disorders

2010 ◽  
Author(s):  
Ann M. Mastergeorge ◽  
Jacky Au
Keyword(s):  
Intellectual Disability ◽  
Fragile X Syndrome ◽  
X Chromosome ◽  
Culture Media ◽  
Fragile Site ◽  
Fragile X ◽  
Single Gene ◽  
Repeat Sequence ◽  
Full Mutation ◽  
Tissue Culture Media

Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability known, and it is the most common single gene disorder associated with autism (Belmonte and Bourgeron 2006; Reddy 2005). It is caused by the lack or deficiency of the FMR1 protein, FMRP (Loesch et al. 2004b). The typical physical features of FXS include prominent ears, hyperextensible finger joints, flat feet, soft skin, and in adolescence and adulthood large testicles (macroorchidism) and a long face (Hagerman 2002b). The behavioral features include poor eye contact, hyperarousal to stimuli, anxiety, hyperactivity, attention deficit, impulsivity, hand stereotypies (such as hand biting and hand flapping), and social deficits including autism and autism spectrum disorder (ASD) (Budimirovic et al. 2006; Clifford et al. 2007; Hall et al. 2008b; Hatton et al. 2006b; Sullivan et al. 2007b). Fragile-X syndrome was first reported by Lubs (1969) in two brothers who had intellectual disability and the appearance of a marker X chromosome, which is a fragile site on their X chromosome. It was later detected that this fragile site on the X chromosome only occurred when the chromosomes were studied in a folate-deficient tissue culture media (Sutherland 1977). Therefore cytogenetic studies were utilized to document cases of FXS throughout the 1980s until the Fragile X Mental Retardation 1 gene (FMR1) was discovered in 1991 (Verkerk et al. 1991). The FMR1 gene was found to have a trinucleotide (CGG) repeat sequence at the 5’ untranslated region, with the normal range later determined to be up to 44 repeats, a gray zone of 45–54 repeats, a premutation of 55–200 repeats, and a full mutation range of more than 200 repeats (Maddalena et al. 2001). Those individuals with the full mutation have a deficit or absence of the FMR1 protein (FMRP) that causes the physical, behavioral, and cognitive features of FXS (Loesch et al. 2004b). Females with the full mutation have another X chromosome that is producing FMRP, depending on the activation ratio (AR) or the percentage of cells that have the normal X chromosome as the active X chromosome.

scholarly journals Urine-Derived Epithelial Cell Lines: A New Tool to Model Fragile X Syndrome (FXS)

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2240
Author(s):  
Marwa Zafarullah ◽  
Mittal Jasoliya ◽  
Flora Tassone
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Fragile X Syndrome ◽  
Cell Lines ◽  
Behavioral Problems ◽  
Cell Model ◽  
Fragile X ◽  
Healthy Controls ◽  
Full Mutation ◽  
Epithelial Cell Lines

Fragile X syndrome (FXS) is an X-linked neurodevelopmental condition associated with intellectual disability and behavioral problems due to the lack of the Fragile X mental retardation protein (FMRP), which plays a crucial role in synaptic plasticity and memory. A desirable in vitro cell model to study FXS would be one that can be generated by simple isolation and culture method from a collection of a non-invasive donor specimen. Currently, the various donor-specific cells can be isolated mainly from peripheral blood and skin biopsy. However, they are somewhat invasive methods for establishing cell lines from the primary subject material. In this study, we characterized a cost-effective and straightforward method to derive epithelial cell lines from urine samples collected from participants with FXS and healthy controls (TD). The urine-derived cells expressed epithelial cell surface markers via fluorescence-activated cell sorting (FACS). We observed inter, and the intra-tissue CGG mosaicism in the PBMCs and the urine-derived cells from participants with FXS potentially related to the observed variations in the phenotypic and clinical presentation FXS. We characterized these urine-derived epithelial cells for FMR1 mRNA and FMRP expression and observed some expression in the lines derived from full mutation mosaic participants. Further, FMRP expression was localized in the cytoplasm of the urine-derived epithelial cells of healthy controls. Deficient FMRP expression was also observed in mosaic males, while, as expected, no expression was observed in cells derived from participants with a hypermethylated full mutation.

Characterisation of a new rare fragile site easily confused with the fragile X

1992 ◽  
Vol 1 (2) ◽  
pp. 111-113 ◽  
Author(s):  
Grant R. Sutherland ◽  
Elizabeth Baker
Keyword(s):  
Fragile Site ◽  
Fragile X

Biallelic deletion and loss of expression analysis of genes at FRA2G common fragile site in tumor-derived cell lines

2005 ◽  
Vol 161 (2) ◽  
pp. 181-186 ◽  
Author(s):  
Zaira M. Limongi ◽  
Angela Curatolo ◽  
Franca Pelliccia ◽  
Angela Rocchi
Keyword(s):  
Cell Lines ◽  
Expression Analysis ◽  
Fragile Site ◽  
Common Fragile Site

Transcriptional profiling of genes at the human common fragile site FRA1H in tumor-derived cell lines

2007 ◽  
Vol 178 (2) ◽  
pp. 144-150 ◽  
Author(s):  
Franca Pelliccia ◽  
Angela Curatolo ◽  
Zaira M. Limongi ◽  
Nazario Bosco ◽  
Angela Rocchi
Keyword(s):  
Cell Lines ◽  
Fragile Site ◽  
Transcriptional Profiling ◽  
Common Fragile Site

Prenatal diagnosis of the fragile-X in male monozygotic twins: Discordant expression of the fragile site in amniocytes

1985 ◽  
Vol 5 (3) ◽  
pp. 229-231 ◽  
Author(s):  
M. Rocchi ◽  
V. Pecile ◽  
N. Archidiacono ◽  
G. Monni ◽  
Y. Dumez ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Fragile Site ◽  
Fragile X ◽  
Monozygotic Twins

The fragile X syndrome I: Familial variation in the proportion of lymphocytes with the fragile site in males

1984 ◽  
Vol 17 (1) ◽  
pp. 241-252 ◽  
Author(s):  
D. Soudek ◽  
M. W. Partington ◽  
J. S. Lawson ◽  
John M. Opitz
Keyword(s):  
Fragile X Syndrome ◽  
Fragile Site ◽  
Fragile X

scholarly journals BASES GENÉTICAS Y BIOLÓGICAS DEL SÍNDROME DE X FRÁGIL

2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Ruth Maribel Forero Castro ◽  
Edwin Javier Vergara Estupiñán ◽  
Jefer Iván Moreno Granados
Keyword(s):  
Mental Retardation ◽  
Fragile X Syndrome ◽  
Messenger Rna ◽  
Fragile Site ◽  
Fragile X ◽  
Normal Population ◽  
Incomplete Penetrance ◽  
Racial Groups ◽  
Full Mutation ◽  
Mendelian Segregation

Después del síndrome de Down, el síndrome de X frágil es la causa más frecuente de retardo mental. Su distribución geográfica es universal y afecta a diferentes grupos raciales. Esta anomalía genética presenta un patrón de herencia ligado a X, dominante, con penetrancia incompleta y anticipación, por lo que revela una segregación no-mendeliana. En 1969, Lubs fue el primero en relacionar el retardo mental con la existencia de un sitio frágil, actualmente reconocido en el brazo largo del cromosoma X en la banda Xq27.3 denominada FRAXA. El gen involucrado en el síndrome de X frágil es el FMR 1, el cual fue identificado en 1991 y su defecto fue atribuido a una expansión del trinucleótido repetitivo CGG, localizado en el primer exón del gen. En la población normal, las repeticiones CGG varían<br />entre un rango de 6 a 54, en individuos portadores entre 43 a 200<br />repeticiones (premutación), mientras que en afectados la expansión de la secuencia CGG tiene más de 200 repeticiones (mutación  completa) y está asociada con la metilación e inactivación del gen. El clonaje del gen FMR 1 condujo a la caracterización de su producto de expresión: la proteína FMRP, involucrada en el metabolismo del RNA y en la función ribosomal. Cuando la región promotora está hipermetilada, se frena la producción del ARN mensajero (ARNm) del gen FMR 1 y, por ende, la producción de la proteína, causando retardo mental, macroorquidismo y otros rasgos físicos y comportamentales característicos del síndrome de X frágil. El diagnóstico del síndrome de X frágil se puede hacer a nivel clínico, citogenético, molecular e inmunohistoquímico, implicando el hallazgo de la fragilidad, la determinación de individuos normales, portadores y afectados, el<br />grado de metilación del gen FMR 1 y la expresión de la proteína FMRP. Aunque este síndrome no tiene cura, el tratamiento en la última década ha sido un foco de interés no solo para los genetistas y médicos generales sino también para otros profesionales, tales como pediatras, psicólogos, trabajadores sociales, logopedas y educadores. El presente artículo tiene como objetivo informar sobre las bases genéticas y biológicas del síndrome de X frágil, y la ruta diagnóstica que debe tenerse en cuenta en el seguimiento de los pacientes y familias afectadas.<br /><br /><strong>Palabras clave:</strong> Síndrome de X frágil, FMR 1, FMRP, retardo mental, premutación, mutación completa.<br /><br /><strong>Abstract</strong><br />Following the Down syndrome, Fragile X Syndrome is the most common cause of mental retardation. Its geographical distribution is universal and affects different racial groups. This genetic anomaly shows a pattern of inheritance linked to X, dominant, with incomplete penetrance and anticipation, so it reveals a non-Mendelian segregation. In 1969, Lubs was the first to link mental retardation with the existence of a fragile site, currently recognised by the long arm of the X chromosome in band Xq27.3 called FRAXA. The gene involved in Fragile X Syndrome is the FMR 1, which was identified in 1991 and its defect was attributed to an expansion of repetitive trinucleotide CGG, located in the first exon of the gene. In the normal population, the CGG repetitions vary from a range of 6 to 54, in carriers between 43 to 200 repetitions (Premutation) while in affected individuals the expansion of the sequence CGG has more than 200 repetitions (Full Mutation) and associated with methylation and gene inactivation. The cloning of the FMR 1 gene led to the characterization of its expression product: FMRP protein, involved in RNA metabolism and<br />ribosomal function. When the promoter region is hypermethylated, it<br />reduces the production of messenger RNA (mRNA) of FMR-1 gene<br />and, thus, the production of the protein, causing mental retardation,<br />macroorquidism and other physical and behavioral traits which are characteristic of Fragile X Syndrome. The diagnosis of Fragile X Syndrome can be made at clinical, cytogenetic, molecular and immunohistochemical level, involving the discovery of the fragility, the determination of normal individuals, carriers and affected persons, <br />the degree of methylation of the FMR-1 gene and expression of<br />FMRP protein. Although this syndrome has no cure, treatment in the<br />last decade has been a source of interest not only for geneticists<br />and general practitioners, but also for other professionals, such as<br />paediatricians, psychologists, social workers, speech therapists and<br />educators. This article aims to report on the biological and genetic<br />bases of the Fragile X Syndrome, and the diagnostic route to be<br />taken into account in the follow-up of patients and families affected.<br /><strong>Keywords:</strong> Fragile X Syndrome, FMR 1, FMRP, mental retardation,<br />premutation, full mutation.

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