Lack of Clinical Differences in X-Linked Mental Retardation with and without Expression of the Fragile Site Xq271

2015 ◽  
pp. 48-52 ◽  
Author(s):  
Angela Schmidt ◽  
E. Passarge
Keyword(s):  
Mental Retardation ◽  
Fragile Site

X-linked mental retardation, macro-orchidism, and the Xq27 fragile site

1980 ◽  
Vol 96 (5) ◽  
pp. 837-841 ◽  
Author(s):  
Gillian Turner ◽  
Art Daniel ◽  
Michael Frost
Keyword(s):  
Mental Retardation ◽  
Fragile Site

DNA studies of X-linked mental retardation associated with a fragile site at Xq27

1986 ◽  
Vol 23 (1-2) ◽  
pp. 633-642 ◽  
Author(s):  
Kay E. Davies ◽  
John M. Opitz ◽  
James F. Reynolds
Keyword(s):  
Mental Retardation ◽  
Fragile Site

Fragile Sites on Chromosomes

PEDIATRICS ◽  
1982 ◽  
Vol 69 (1) ◽  
pp. 121-123
Author(s):  
Frederick Hecht ◽  
Thomas W. Glover ◽  
Barbara Kaiser-Hecht
Keyword(s):  
Mental Retardation ◽  
X Chromosome ◽  
Fanconi Anemia ◽  
Ataxia Telangiectasia ◽  
Autosomal Recessive ◽  
Fragile Site ◽  
Chromosome Instability ◽  
Chromosome Complement ◽  
Fragile Sites ◽  
Chromosome Fragility

A fragile site on the X chromosome is associated with a common form of mental retardation in males and a proportion of females.1-3 This association was not fully appreciated when the fragile site on the X was first described in 1969,4 but it is crystal-clear today. Chromosome fragility can be random, as in Fanconi anemia, Bloom syndrome, and ataxia-telangiectasia, the chromosome instability syndromes.5 Breaks and rearrangements of chromosomes are seen in these disorders, all of which are autosomal recessive conditions predisposing to cancer. Fragile sites are special spots in the genome where gaps and breaks occur nonrandomly. The balance of the chromosome complement is normal.

Study of a family with a fragile site of the X chromosome at Xq27–28 without mental retardation

1989 ◽  
Vol 81 (4) ◽  
pp. 353-357 ◽  
Author(s):  
M. A. Voelckel ◽  
N. Philip ◽  
C. Piquet ◽  
M. C. Pellissier ◽  
I. Oberlé ◽  
...  
Keyword(s):  
Mental Retardation ◽  
X Chromosome ◽  
Fragile Site

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.

Health Supervision for Children With Fragile X Syndrome

PEDIATRICS ◽  
1996 ◽  
Vol 98 (2) ◽  
pp. 297-300
Author(s):  
Keyword(s):  
Mental Retardation ◽  
Developmental Delay ◽  
Fragile X Syndrome ◽  
X Chromosome ◽  
Dna Analysis ◽  
Fragile Site ◽  
Fragile X ◽  
Physical Features ◽  
Relationship Of ◽  
The Relationship

This set of guidelines is designed to assist pediatricians in caring for children with fragile X syndrome confirmed by DNA analysis (Table). Occasionally pediatricians are called on to advise a pregnant woman who has been informed of a prenatal diagnosis of fragile X syndrome. Therefore, guidelines are also offered for this situation. Fragile X syndrome is usually diagnosed during childhood and is characterized by developmental delay or mental retardation, characteristic physical features, and abnormal behavioral patterns.1,2 The distinctive fragile site on the X chromosome was first described in 1969 as a discontinuous site on the long arm of the X chromosome present after cell culture under folate-deficient conditions. In 1977 the relationship of this site to X-linked mental retardation was noted, and fragile X syndrome began to be defined. Since that time, the cytogenetic, molecular, and clinical features of the condition have been more clearly defined,3 and it is now recognized as the most common hereditary cause of mental retardation. Its frequency has been estimated to be approximately per 2500 to 1 per 1250 males and 1 per 5000 to 1 per 1600 females. The phenotype of fragile X syndrome in males often has a number of distinctive, recognizable features, including developmental delay or mental retardation, a prominent forehead, a long, thin face and a prominent jaw that appear late in childhood or early adolescence, large protuberant and slightly dysmorphic ears, and the presence of or ultimate development of macro-orchidism. This phenotype can be very subtle, is not always apparent, and becomes more identifiable with age.2

Dissociation between mental retardation and fragile site expression in a family with fragile X-linked mental retardation

1988 ◽  
Vol 80 (4) ◽  
pp. 375-378 ◽  
Author(s):  
M. A. Voelckel ◽  
M. G. Mattei ◽  
C. N'Guyen ◽  
N. Philip ◽  
F. Birg ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Fragile Site ◽  
Fragile X

scholarly journals Experience with molecular and cytogenetic diagnosis of fragile X syndrome in Brazilian families

1997 ◽  
Vol 20 (4) ◽  
pp. 731-739 ◽  
Author(s):  
Regina C. Mingroni-Netto ◽  
Rita C.M. Pavanello ◽  
Paulo A. Otto ◽  
Angela M. Vianna-Morgante
Keyword(s):  
Mental Retardation ◽  
Dna Analysis ◽  
Fragile Site ◽  
Fragile X ◽  
False Negative ◽  
Full Mutation ◽  
Negative Results ◽  
Cgg Repeats ◽  
False Negative Results ◽  
Normal Males

We report on the cytogenetic and DNA analysis of 55 families with the fragile X (FMR-1 locus) mutation (318 individuals and 15 chorionic villi samples). A total of 129 males were investigated, 54 mentally normal and 75 presenting mental retardation. Among the 54 normal males, 11 had the premutation, and none expressed the fragile site. The full mutation was detected in 73 retarded males, and 14 (18%) presented a premutation along with the full mutation (mosaics). All of them manifested the fragile site. The frequencies of fragile site expression correlated positively with the sizes of the expansion of the CGG repeats (<FONT FACE="Symbol">D</FONT>). Among 153 normal females, 85 were found to be heterozygous for the premutation and 15 had the full mutation. In the premutated females the fragile site was not observed or it occurred at frequencies that did not differ from those observed in 53 noncarriers. Cytogenetic analysis was thus ineffective for the diagnosis of premutated males or females. Among the 51 heterozygotes for the full mutation, 36 (70%) had some degree of mental impairment. As in males, a positive correlation was detected between the frequencies of fragile site manifestation and the size of the expansion. However, the cytogenetic test was less effective for the detection of fully mutated females, than in the case of males, since 14% false negative results were found among females. Segregation analysis confirmed that the risk of mental retardation in the offspring of heterozygotes increases with the length of <FONT FACE="Symbol">D</FONT>. The average observed frequency of mental retardation in the offspring of all heterozygotes was 30%. There was no indication of meiotic drive occurring in female carriers, since the number of individuals who inherited the mutation did not differ from the number of those inheriting the normal allele. No new mutations were detected in the 55 genealogies studied here.

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