scholarly journals Molecular Testing for Fragile X: Analysis of 5062 Tests from 1105 Fragile X Families—Performed in 12 Clinical Laboratories in Spain

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
María-Isabel Tejada ◽  
Guillermo Glover ◽  
Francisco Martínez ◽  
Miriam Guitart ◽  
Yolanda de Diego-Otero ◽  
...  
Keyword(s):  
Klinefelter Syndrome ◽  
Fragile X ◽  
Female Offspring ◽  
Molecular Diagnostic ◽  
Molecular Testing ◽  
Full Mutation ◽  
Premutation Allele ◽  
Full Mutation Allele ◽  
Intermediate Alleles ◽  
Mutation Allele

Fragile X syndrome is the most common inherited form of intellectual disability. Here we report on a study based on a collaborative registry, involving 12 Spanish centres, of molecular diagnostic tests in 1105 fragile X families comprising 5062 individuals, of whom, 1655 carried a full mutation or were mosaic, three cases had deletions, 1840 had a premutation, and 102 had intermediate alleles. Two patients with the full mutation also had Klinefelter syndrome. We have used this registry to assess the risk of expansion from parents to children. From mothers with premutation, the overall rate of allele expansion to full mutation is 52.5%, and we found that this rate is higher for male than female offspring (63.6% versus 45.6%;P<0.001). Furthermore, in mothers with intermediate alleles (45–54 repeats), there were 10 cases of expansion to a premutation allele, and for the smallest premutation alleles (55–59 repeats), there was a 6.4% risk of expansion to a full mutation, with 56 repeats being the smallest allele that expanded to a full mutation allele in a single meiosis. Hence, in our series the risk for alleles of<59 repeats is somewhat higher than in other published series. These findings are important for genetic counselling.

scholarly journals Prenatal Diagnosis of Fragile X: Can a Full Mutation Allele in the FMR1 Gene Contract to a Normal Size?

2017 ◽  
Vol 8 ◽  
Author(s):  
Esther Manor ◽  
Azhar Jabareen ◽  
Nurit Magal ◽  
Arei Kofman ◽  
Randi J. Hagerman ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Fragile X ◽  
Fmr1 Gene ◽  
Full Mutation ◽  
Full Mutation Allele ◽  
Mutation Allele

scholarly journals Study of telomere length in men who carry a fragile X premutation or full mutation allele

2020 ◽  
Vol 139 (12) ◽  
pp. 1531-1539
Author(s):  
Igor Albizua ◽  
Pankaj Chopra ◽  
Emily G. Allen ◽  
Weiya He ◽  
Ashima S. Amin ◽  
...  
Keyword(s):  
Telomere Length ◽  
Fragile X ◽  
Full Mutation ◽  
Fragile X Premutation ◽  
Full Mutation Allele ◽  
Mutation Allele

scholarly journals Cascade Testing for Fragile X Syndrome in a Rural Setting in Cameroon (Sub-Saharan Africa)

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 136
Author(s):  
Karen Kengne Kamga ◽  
Séraphin Nguefack ◽  
Khuthala Minka ◽  
Edmond Wonkam Tingang ◽  
Alina Esterhuizen ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Fragile X ◽  
Autism Spectrum ◽  
Sub Saharan Africa ◽  
Rural Setting ◽  
Premature Menopause ◽  
Molecular Testing ◽  
Full Mutation ◽  
Cgg Repeat ◽  
Cgg Repeats

Fragile X Syndrome (FXS), an X-linked dominant monogenic condition, is the main genetic cause of intellectual disability (ID) and autism spectrum disorder (ASD). FXS is associated with an expansion of CGG repeat sequence in the Fragile X Mental Retardation gene 1 (FMR1) on chromosome X. Following a neuropediatric assessment of two male siblings who presented with signs of FXS that was confirmed with molecular testing, we provided cascade counselling and testing to the extended family. A total of 46 individuals were tested for FXS; among them, 58.70% (n = 27) were females. The mean age was 9.4 (±5) years for children and 45.9 (±15.9) years for adults. Pedigree analysis suggested that the founder of these families was likely a normal transmitting male. Four out of 19 males with clinical ID were confirmed to have a full mutation for FXS, while 14/27 females had a pathologic CGG expansion (>56 CGG repeats) on one of their X chromosomes. Two women with premature menopause were confirmed of being carriers of premutation (91 and 101 CGG repeats). We also identified maternal alleles (91 and 126 CGG repeats) which expanded to a full mutation in their offspring (>200 CGG repeats). This study is a rare report on FXS from Africa and illustrates the case scenario of implementing genetic medicine for a neurogenetic condition in a rural setting.

Mosaicism in Fragile X syndrome: A family case series

2021 ◽  
pp. 174462952199534
Author(s):  
Wilmar Saldarriaga ◽  
Laura Yuriko González-Teshima ◽  
Jose Vicente Forero-Forero ◽  
Hiu-Tung Tang ◽  
Flora Tassone
Keyword(s):  
Mental Retardation ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Fmr1 Gene ◽  
Molecular Testing ◽  
Full Mutation ◽  
Mild Phenotype ◽  
Variable Expression ◽  
Fragile X Mental Retardation ◽  
Classic Phenotype

Fragile X syndrome (FXS) has a classic phenotype, however its expression can be variable among full mutation males. This is secondary to variable methylation mosaicisms and the number of CGG triplet repeats in the non-coding region of the Fragile X Mental Retardation 1 ( FMR1) gene, producing a variable expression of the Fragile X Mental Retardation Protein (FMRP). Here we report a family with several individuals affected by FXS: a boy with a hypermethylated FMR1 mutation and a classic phenotype; a man with an FMR1 gene mosaicism in the range of premutation (PM) and full mutation (FM), who has a mild phenotype due to which FXS was initially disregarded; and the cases of four women with a FM and mosaicism. This report highlights the importance of DNA molecular testing for the diagnosis of FXS in patients with developmental delay, intellectual disability and/or autism due to the variable phenotype that occurs in individuals with FMR1 mosaicisms.

Paternal transmission of a FMR1 full mutation allele

2017 ◽  
Vol 173 (10) ◽  
pp. 2795-2797 ◽  
Author(s):  
Maria Isabel Alvarez-Mora ◽  
Miriam Guitart ◽  
Laia Rodriguez-Revenga ◽  
Irene Madrigal ◽  
Elisabeth Gabau ◽  
...  
Keyword(s):  
Full Mutation ◽  
Paternal Transmission ◽  
Full Mutation Allele ◽  
Mutation Allele

scholarly journals Urine microRNA Profiling Displays miR-125a Dysregulation in Children with Fragile X Syndrome

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 289
Author(s):  
Noora Putkonen ◽  
Asta Laiho ◽  
Doug Ethell ◽  
Juha Pursiheimo ◽  
Anna-Kaisa Anttonen ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Metabotropic Glutamate Receptor ◽  
Fragile X ◽  
Type I ◽  
Neuronal Function ◽  
Full Mutation ◽  
Treatment Target ◽  
Metabotropic Glutamate ◽  
Triplet Repeat Expansion ◽  
Premutation Allele

A triplet repeat expansion leading to transcriptional silencing of the FMR1 gene results in fragile X syndrome (FXS), which is a common cause of inherited intellectual disability and autism. Phenotypic variation requires personalized treatment approaches and hampers clinical trials in FXS. We searched for microRNA (miRNA) biomarkers for FXS using deep sequencing of urine and identified 28 differentially regulated miRNAs when 219 reliably identified miRNAs were compared in dizygotic twin boys who shared the same environment, but one had an FXS full mutation, and the other carried a premutation allele. The largest increase was found in miR-125a in the FXS sample, and the miR-125a levels were increased in two independent sets of urine samples from a total of 19 FXS children. Urine miR-125a levels appeared to increase with age in control subjects, but varied widely in FXS subjects. Should the results be generalized, it could suggest that two FXS subgroups existed. Predicted gene targets of the differentially regulated miRNAs are involved in molecular pathways that regulate developmental processes, homeostasis, and neuronal function. Regulation of miR-125a has been associated with type I metabotropic glutamate receptor signaling (mGluR), which has been explored as a treatment target for FXS, reinforcing the possibility that urine miR-125a may provide a novel biomarker for FXS.

scholarly journals Detection of Cryptic Fragile X Full Mutation Alleles by Southern Blot in a Female and Her Foetal DNA via Chorionic Villus Sampling, Complicated by Mosaicism for 45,X0/46,XX/47,XXX

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 798
Author(s):  
Alison Pandelache ◽  
David Francis ◽  
Ralph Oertel ◽  
Rebecca Dickson ◽  
Rani Sachdev ◽  
...  
Keyword(s):  
Southern Blot ◽  
Fragile X ◽  
Chorionic Villus ◽  
Prenatal Testing ◽  
Chorionic Villus Sampling ◽  
Full Mutation ◽  
Fmr1 Premutation ◽  
Full Mutation Allele ◽  
History Of ◽  
Polymerase Chain

We describe a female with a 72 CGG FMR1 premutation (PM) (CGG 55–199) and family history of fragile X syndrome (FXS), referred for prenatal testing. The proband had a high risk of having an affected pregnancy with a full mutation allele (FM) (CGG > 200), that causes FXS through hypermethylation of the FMR1 promoter. The CGG sizing analysis in this study used AmplideX triplet repeat primed polymerase chain reaction (TP-PCR) and long-range methylation sensitive PCR (mPCR). These methods detected a 73 CGG PM allele in the proband’s blood, and a 164 CGG PM allele in her male cultured chorionic villus sample (CVS). In contrast, the Southern blot analysis showed mosaicism for: (i) a PM (71 CGG) and an FM (285–768 CGG) in the proband’s blood, and (ii) a PM (165 CGG) and an FM (408–625 CGG) in the male CVS. The FMR1 methylation analysis, using an EpiTYPER system in the proband, showed levels in the range observed for mosaic Turner syndrome. This was confirmed by molecular and cytogenetic karyotyping, identifying 45,X0/46,XX/47,XXX lines. In conclusion, this case highlights the importance of Southern blot in pre- and postnatal testing for presence of an FM, which was not detected using AmplideX TP-PCR or mPCR in the proband and her CVS.

scholarly journals A Pseudo-Full Mutation Identified in Fragile X Assay Reveals a Novel Base Change Abolishing an EcoRI Restriction Site

2008 ◽  
Vol 10 (5) ◽  
pp. 469-474 ◽  
Author(s):  
Shujian Liang ◽  
Harold N. Bass ◽  
Hanlin Gao ◽  
Caroline Astbury ◽  
Mehdi R. Jamehdor ◽  
...  
Keyword(s):  
Restriction Site ◽  
Fragile X ◽  
Base Change ◽  
Full Mutation ◽  
Ecori Restriction

Learning-disabled Males With a Fragile X CGG Expansion in the Upper Premutation Size Range

PEDIATRICS ◽  
1996 ◽  
Vol 97 (1) ◽  
pp. 122-126
Author(s):  
Randi J. Hagerman ◽  
Louise W. Staley ◽  
Rebecca O'Conner ◽  
Kellie Lugenbeel ◽  
David Nelson ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Fragile X Syndrome ◽  
Size Range ◽  
Cpg Island ◽  
Fragile X ◽  
Learning Disabled ◽  
Full Mutation ◽  
Cgg Repeat ◽  
Responsible Gene ◽  
Repeat Segment

There is a broad spectrum of clinical involvement in both boys and girls affected by fragile X syndrome. Although this disorder is best known as the most common inherited cause of mental retardation, it also can manifest as learning disabilities in individuals with IQs in the broad range of normal. Boys are usually retarded, and girls are usually learning disabled with fragile X syndrome.1 The responsible gene, fragile X mental retardation 1 (FMR1), was isolated in 1991, and the mutation was found to involve expansion of a trinucleotide (CGG) repeat segment. Individuals with fragile X syndrome have a CGG expansion of more than 200 repeats associated with hypermethylation of both the expansion and an adjacent CpG island (full mutation).2,3

Molecular Testing of Solid Tumors

2011 ◽  
Vol 135 (1) ◽  
pp. 67-82 ◽  
Author(s):  
Anne Igbokwe ◽  
Dolores H. Lopez-Terrada
Keyword(s):  
Solid Tumors ◽  
Solid Tumor ◽  
Unknown Origin ◽  
Standard Of Care ◽  
Soft Tissue Tumors ◽  
Molecular Diagnostic ◽  
Original Research ◽  
Molecular Testing ◽  
Neoplastic Disease ◽  
Therapeutic Decisions

Abstract Context—Molecular testing of solid tumors is steadily becoming a vital component of the contemporary anatomic pathologist's armamentarium. These sensitive and specific ancillary tools are useful for confirming ambiguous diagnoses suspected by light microscopy and for guiding therapeutic decisions, assessing prognosis, and monitoring patients for residual neoplastic disease after therapy. Objective—To review current molecular biomarkers and tumor-specific assays most useful in solid tumor testing, specifically of breast, colon, lung, thyroid, and soft tissue tumors, malignant melanoma, and tumors of unknown origin. A few upcoming molecular diagnostic assays that may become standard of care in the near future will also be discussed. Data Sources—Original research articles, review articles, and the authors' personal practice experience. Conclusions—Molecular testing in anatomic pathology is firmly established and will continue to gain ground as the need for more specific diagnoses and new targeted therapies evolve. Knowledge of the more common and clinically relevant molecular tests available for solid tumor diagnosis and management, and their indications and limitations, is necessary if anatomic pathologists are to optimally use these tests and act as consultants for fellow clinicians directly involved in patient care.

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