Evaluation of clinical checklists for fragile X syndrome screening in Brazilian intellectually disabled males

Christofolini, Denise Maria; Abbud, Eduardo M.; Lipay, Mônica Vannucci Nunes; Costa, Silvia Souza da; Vianna‐Morgante, Angela Maria; Bellucco, Fernanda Teixeira da Silva; Nogueira, Sintia I.; Kulikowski, Leslie Domenici; Brunoni, Décio; Juliano, Yára; Ramos, Marco A.; Melaragno, Maria Isabel

doi:10.1177/1744629509348429

Cited by 11 publications

(14 citation statements)

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“…Although, a number of studies have been carried out reporting prevalence of FXS in different populations (Crawford et al, 2001;Puusepp et al, 2008;Essop & Krause, 2013;Tejada et al, 2014), knowledge in Latin America is relatively scant (Lacassie et al, 1983;Florencia et al, 2006;Christofolini et al, 2009). Although, a number of studies have been carried out reporting prevalence of FXS in different populations (Crawford et al, 2001;Puusepp et al, 2008;Essop & Krause, 2013;Tejada et al, 2014), knowledge in Latin America is relatively scant (Lacassie et al, 1983;Florencia et al, 2006;Christofolini et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

FMR1 gene mutations in patients with fragile X syndrome and obligate carriers: 30 years of experience in Chile

et al. 2016

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Fragile X syndrome (FXS) is the most common form of inherited intellectual disability (ID) and co-morbid autism. It is caused by an amplification of the CGG repeat (>200), which is known as the full mutation, within the 5'UTR of the FMR1 gene. Expansions between 55-200 CGG repeats are termed premutation and are associated with a greater risk for fragile X-associated tremor/ataxia syndrome and fragile X-associated premature ovarian insufficiency. Intermediate alleles, also called the grey zone, include approximately 45-54 repeats and are considered borderline. Individuals with less than 45 repeats have a normal FMR1 gene. We report the occurrence of CGG expansions of the FMR1 gene in Chile among patients with ID and families with a known history of FXS. Here, we present a retrospective review conducted on 2321 cases (2202 probands and 119 relatives) referred for FXS diagnosis and cascade screening at the Institute of Nutrition and Food Technology (INTA), University of Chile. Samples were analysed using traditional cytogenetic methods and/or PCR. Southern blot was used to confirm the diagnosis. Overall frequency of FMR1 expansions observed among probands was 194 (8·8%), the average age of diagnosis was 8·8 ± 5·4 years. Of 119 family members studied, 72 (60%) were diagnosed with a CGG expansion. Our results indicated that the prevalence of CGG expansions of the FMR1 gene among probands is relatively higher than other populations. The average age of diagnosis is also higher than reference values. PCR and Southern blot represent a reliable molecular technique in the diagnosis of FXS.

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Section: Discussionmentioning

confidence: 99%

FMR1 gene mutations in patients with fragile X syndrome and obligate carriers: 30 years of experience in Chile

et al. 2016

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“…The key clinical features present in adolescent males are ID, long narrow face, large and prominent ears, attention deficits, hyperactivity, often autistic behavior, and macro‐orchidism. The phenotype is quite unremarkable in young children but progresses with age [Hagerman and Hagerman, ; Christofolini et al, ; Hersh et al, ].…”

Section: Introductionmentioning

confidence: 99%

Frequency of FMR1 gene mutation and CGG repeat polymorphism in intellectually disabled children in Pakistan

Fatima

Zaidi

Sarfraz

et al. 2014

American J of Med Genetics Pt A

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Fragile X syndrome is considered the most common heritable form of X-linked intellectual disability (ID). The syndrome is caused by silencing of the fragile X mental retardation 1 gene (Xq27.3) due to hypermethylation. This mutation results in absence or deficit of its protein product, the fragile X mental retardation protein (FMRP) that affects synaptic plasticity in neurons, hence leads to brain dysfunction. The syndrome is widely distributed throughout the world. This study reported for the first time the frequency of the fragile X mental retardation 1 gene mutations in intellectually disabled children in Pakistan. We recruited 333 intellectually disabled children and 250 normal children with age ranging from 5 to 18 years for this study. Genomic DNA was extracted from peripheral blood and full mutations were identified by methylation sensitive PCR using primers corresponding to modified methylated and unmethylated DNA. Southern blot was used for confirmation of the results. The frequency of fragile X syndrome with full mutation was found as 4.8%. It was 6.5% in males as opposed to 0.9% in females; 29 CGG repeats were found as the most common allele; 31.5% in the intellectually disabled and 34% in control subjects. In Pakistan intellectual disability is considered as a social stigma for the individuals and their families. Due to lack of knowledge and cultural background people make such patients and families isolated. This study will increase public awareness about the intellectual disability and importance of prenatal screening and genetic counseling for vulnerable families.

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“…Table 1 summarizes the characteristics of included studies. It shows that six studies were from North America and Europe (Arvio, Peippo, & Simola, 1997;Bellavance & Morin, 2017;Butler, Brunschwig, Miller, & Hagerman, 1992;Hagerman et al, 1991;Lachiewicz, Dawson, & Spiridigliozzi, 2000;de Vries, Halley, Oostra, & Niermeijer, 1998), two from South to Central Asia (Guruju et al, 2009;Kanwal et al, 2015), two from Latin America and the Caribbean (Boy, Correia, Llerena, Machado-Ferreira, & Pimentel, 2001;Christofolini et al, 2009), and one from Africa (Behery, 2008). We did come across two interesting fragile X syndrome studies from Sub-Saharan Africa, but none of them met the criteria to be included in this study (Essop & Krause, 2013;Peprah, Allen, Williams, Woodard, & Sherman, 2010).…”

Section: Resultsmentioning

confidence: 99%

Fragile X checklists: A meta‐analysis and development of a simplified universal clinical checklist

Lubala

Lumaka

Kanteng

et al. 2018

Molec Gen & Gen Med

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BackgroundClinical checklists available have been developed to assess the risk of a positive Fragile X syndrome but they include relatively small sample sizes. Therefore, we carried out a meta‐analysis that included statistical pooling of study results to obtain accurate figures on the prevalence of clinical predictors of Fragile X syndrome among patients with intellectual disability, thereby helping health professionals to improve their referrals for Fragile X testing.MethodsAll published studies consisting of cytogenetic and/or molecular screening for fragile X syndrome among patients with intellectual disability, were eligible for the meta‐analysis. All patients enrolled in clinical checklists trials of Fragile X syndrome were eligible for this review, with no exclusion based on ethnicity or age. Odds ratio values, with 95% confidence intervals as well as Cronbach coefficient alpha, was reported to assess the frequency of clinical characteristics in subjects with intellectual disability with and without the fragile X mutation to determine the most discriminating.ResultsThe following features were strongly associated with Fragile X syndrome: skin soft and velvety on the palms with redundancy of skin on the dorsum of hand [OR: 16.85 (95% CI 10.4–27.3; α:0.97)], large testes [OR: 7.14 (95% CI 5.53–9.22; α: 0.80)], large and prominent ears [OR: 18.62 (95% CI 14.38–24.1; α: 0.98)], pale blue eyes [OR: 8.97 (95% CI 4.75–16.97; α: 0.83)], family history of intellectual disability [OR: 3.43 (95% CI 2.76–4.27; α: 0.81)] as well as autistic‐like behavior [OR: 3.08 (95% CI 2.48–3.83; α: 0.77)], Flat feet [OR: 11.53 (95% CI 6.79–19.56; α:0.91)], plantar crease [OR: 3.74 (95% CI 2.67–5.24; α: 0.70)]. We noted a weaker positive association between transverse palmar crease [OR: 2.68 (95% CI 1.70–4.18; α: 0.51)], elongated face [OR: 3.69 (95% CI 2.84–4.81; α: 0.63)]; hyperextensible metacarpo‐phalangeal joints [OR: 2.68 (95% CI 2.15–3.34; α: 0.57)] and the Fragile X syndrome.ConclusionThis study has identified the highest risk features for patients with Fragile X syndrome that have been used to design a universal clinical checklist.

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Evaluation of clinical checklists for fragile X syndrome screening in Brazilian intellectually disabled males

Cited by 11 publications

References 20 publications

FMR1 gene mutations in patients with fragile X syndrome and obligate carriers: 30 years of experience in Chile

FMR1 gene mutations in patients with fragile X syndrome and obligate carriers: 30 years of experience in Chile

Frequency of FMR1 gene mutation and CGG repeat polymorphism in intellectually disabled children in Pakistan

Fragile X checklists: A meta‐analysis and development of a simplified universal clinical checklist

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