Genetic cluster of fragile X syndrome in a Colombian district

Wilmar Saldarriaga, Jose Vicente Forero-Forero, Laura Yuriko González-Teshima, Andrés Fandiño-Losada, Carolina Isaza, Jose Rafael Tovar-Cuevas, Marisol Silva, Nimrah S. Choudhary, Hiu Tung Tang, Sergio Aguilar-Gaxiola, Randi J Hagerman, Flora Tassone

Research output: Contribution to journalArticle

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Abstract

Background:: Fragile X syndrome (FXS) is the most common cause of inherited intellectual disabilities and autism. The reported prevalence of the full mutation (FM) gene FMR1 in the general population is 0.2–0.4 per 1000 males and 0.125–0.4 per 1000 females. Population screening for FMR1 expanded alleles has been performed in newborns and in an adult population. However, it has never been carried out in an entire town. Ricaurte is a Colombian district with 1186 habitants, with a high prevalence of FXS, which was first described by cytogenetic techniques in 1999. Methods:: Using a PCR-based approach, screening for FXS was performed on blood spot samples obtained from 926 (502 males and 424 females) inhabitants from Ricaurte, accounting for 78% of total population. Results:: A high prevalence of carriers of the expanded allele was observed in all FXS mutation categories. Using the Bayesian methods the carrier frequency of FM was 48.2 (95% Credibility Region CR: 36.3–61.5) per 1000 males and 20.5 (95% CR:13.5–28.6) per 1000 females; the frequency of premutation carrier was 14.1 (95% RC: 8.0–21.7) per 1000 males (95% RC: 8.0–21.7 per 1000 males) and 35.9 (95% RC: 26.5–46.2) per 1000 for females (95% RC: 26.5–46.2 per 1000 females), and gray zone carrier was 13.4 (95% RC: 7.4–20.7) per 1000 males (95% RC: 7.4–20.7 per 1000 males) and 42.2 (95% RC: 32.2–53.8) per 1000 for females (95% RC: 32.2–53.8 per 1000 females). Differences in carrier frequencies were observed for premutation and FM alleles between natives and non-natives. Conclusions:: This study shows that in Ricaurte the carrier frequencies of FMR1 expanded alleles (premutations and FMs) are higher than those reported in the literature, suggesting that Ricaurte constitutes a genetic cluster of FXS.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalJournal of Human Genetics
DOIs
StateAccepted/In press - Jan 29 2018

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Fragile X Syndrome
Alleles
Mutation
Population
Bayes Theorem
Cytogenetic Analysis
Mutation Rate
Autistic Disorder
Population Groups
Intellectual Disability
Newborn Infant
Polymerase Chain Reaction
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Saldarriaga, W., Forero-Forero, J. V., González-Teshima, L. Y., Fandiño-Losada, A., Isaza, C., Tovar-Cuevas, J. R., ... Tassone, F. (Accepted/In press). Genetic cluster of fragile X syndrome in a Colombian district. Journal of Human Genetics, 1-8. https://doi.org/10.1038/s10038-017-0407-6

Genetic cluster of fragile X syndrome in a Colombian district. / Saldarriaga, Wilmar; Forero-Forero, Jose Vicente; González-Teshima, Laura Yuriko; Fandiño-Losada, Andrés; Isaza, Carolina; Tovar-Cuevas, Jose Rafael; Silva, Marisol; Choudhary, Nimrah S.; Tang, Hiu Tung; Aguilar-Gaxiola, Sergio; Hagerman, Randi J; Tassone, Flora.

In: Journal of Human Genetics, 29.01.2018, p. 1-8.

Research output: Contribution to journalArticle

Saldarriaga, W, Forero-Forero, JV, González-Teshima, LY, Fandiño-Losada, A, Isaza, C, Tovar-Cuevas, JR, Silva, M, Choudhary, NS, Tang, HT, Aguilar-Gaxiola, S, Hagerman, RJ & Tassone, F 2018, 'Genetic cluster of fragile X syndrome in a Colombian district', Journal of Human Genetics, pp. 1-8. https://doi.org/10.1038/s10038-017-0407-6
Saldarriaga W, Forero-Forero JV, González-Teshima LY, Fandiño-Losada A, Isaza C, Tovar-Cuevas JR et al. Genetic cluster of fragile X syndrome in a Colombian district. Journal of Human Genetics. 2018 Jan 29;1-8. https://doi.org/10.1038/s10038-017-0407-6
Saldarriaga, Wilmar ; Forero-Forero, Jose Vicente ; González-Teshima, Laura Yuriko ; Fandiño-Losada, Andrés ; Isaza, Carolina ; Tovar-Cuevas, Jose Rafael ; Silva, Marisol ; Choudhary, Nimrah S. ; Tang, Hiu Tung ; Aguilar-Gaxiola, Sergio ; Hagerman, Randi J ; Tassone, Flora. / Genetic cluster of fragile X syndrome in a Colombian district. In: Journal of Human Genetics. 2018 ; pp. 1-8.
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abstract = "Background:: Fragile X syndrome (FXS) is the most common cause of inherited intellectual disabilities and autism. The reported prevalence of the full mutation (FM) gene FMR1 in the general population is 0.2–0.4 per 1000 males and 0.125–0.4 per 1000 females. Population screening for FMR1 expanded alleles has been performed in newborns and in an adult population. However, it has never been carried out in an entire town. Ricaurte is a Colombian district with 1186 habitants, with a high prevalence of FXS, which was first described by cytogenetic techniques in 1999. Methods:: Using a PCR-based approach, screening for FXS was performed on blood spot samples obtained from 926 (502 males and 424 females) inhabitants from Ricaurte, accounting for 78{\%} of total population. Results:: A high prevalence of carriers of the expanded allele was observed in all FXS mutation categories. Using the Bayesian methods the carrier frequency of FM was 48.2 (95{\%} Credibility Region CR: 36.3–61.5) per 1000 males and 20.5 (95{\%} CR:13.5–28.6) per 1000 females; the frequency of premutation carrier was 14.1 (95{\%} RC: 8.0–21.7) per 1000 males (95{\%} RC: 8.0–21.7 per 1000 males) and 35.9 (95{\%} RC: 26.5–46.2) per 1000 for females (95{\%} RC: 26.5–46.2 per 1000 females), and gray zone carrier was 13.4 (95{\%} RC: 7.4–20.7) per 1000 males (95{\%} RC: 7.4–20.7 per 1000 males) and 42.2 (95{\%} RC: 32.2–53.8) per 1000 for females (95{\%} RC: 32.2–53.8 per 1000 females). Differences in carrier frequencies were observed for premutation and FM alleles between natives and non-natives. Conclusions:: This study shows that in Ricaurte the carrier frequencies of FMR1 expanded alleles (premutations and FMs) are higher than those reported in the literature, suggesting that Ricaurte constitutes a genetic cluster of FXS.",
author = "Wilmar Saldarriaga and Forero-Forero, {Jose Vicente} and Gonz{\'a}lez-Teshima, {Laura Yuriko} and Andr{\'e}s Fandi{\~n}o-Losada and Carolina Isaza and Tovar-Cuevas, {Jose Rafael} and Marisol Silva and Choudhary, {Nimrah S.} and Tang, {Hiu Tung} and Sergio Aguilar-Gaxiola and Hagerman, {Randi J} and Flora Tassone",
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T1 - Genetic cluster of fragile X syndrome in a Colombian district

AU - Saldarriaga, Wilmar

AU - Forero-Forero, Jose Vicente

AU - González-Teshima, Laura Yuriko

AU - Fandiño-Losada, Andrés

AU - Isaza, Carolina

AU - Tovar-Cuevas, Jose Rafael

AU - Silva, Marisol

AU - Choudhary, Nimrah S.

AU - Tang, Hiu Tung

AU - Aguilar-Gaxiola, Sergio

AU - Hagerman, Randi J

AU - Tassone, Flora

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N2 - Background:: Fragile X syndrome (FXS) is the most common cause of inherited intellectual disabilities and autism. The reported prevalence of the full mutation (FM) gene FMR1 in the general population is 0.2–0.4 per 1000 males and 0.125–0.4 per 1000 females. Population screening for FMR1 expanded alleles has been performed in newborns and in an adult population. However, it has never been carried out in an entire town. Ricaurte is a Colombian district with 1186 habitants, with a high prevalence of FXS, which was first described by cytogenetic techniques in 1999. Methods:: Using a PCR-based approach, screening for FXS was performed on blood spot samples obtained from 926 (502 males and 424 females) inhabitants from Ricaurte, accounting for 78% of total population. Results:: A high prevalence of carriers of the expanded allele was observed in all FXS mutation categories. Using the Bayesian methods the carrier frequency of FM was 48.2 (95% Credibility Region CR: 36.3–61.5) per 1000 males and 20.5 (95% CR:13.5–28.6) per 1000 females; the frequency of premutation carrier was 14.1 (95% RC: 8.0–21.7) per 1000 males (95% RC: 8.0–21.7 per 1000 males) and 35.9 (95% RC: 26.5–46.2) per 1000 for females (95% RC: 26.5–46.2 per 1000 females), and gray zone carrier was 13.4 (95% RC: 7.4–20.7) per 1000 males (95% RC: 7.4–20.7 per 1000 males) and 42.2 (95% RC: 32.2–53.8) per 1000 for females (95% RC: 32.2–53.8 per 1000 females). Differences in carrier frequencies were observed for premutation and FM alleles between natives and non-natives. Conclusions:: This study shows that in Ricaurte the carrier frequencies of FMR1 expanded alleles (premutations and FMs) are higher than those reported in the literature, suggesting that Ricaurte constitutes a genetic cluster of FXS.

AB - Background:: Fragile X syndrome (FXS) is the most common cause of inherited intellectual disabilities and autism. The reported prevalence of the full mutation (FM) gene FMR1 in the general population is 0.2–0.4 per 1000 males and 0.125–0.4 per 1000 females. Population screening for FMR1 expanded alleles has been performed in newborns and in an adult population. However, it has never been carried out in an entire town. Ricaurte is a Colombian district with 1186 habitants, with a high prevalence of FXS, which was first described by cytogenetic techniques in 1999. Methods:: Using a PCR-based approach, screening for FXS was performed on blood spot samples obtained from 926 (502 males and 424 females) inhabitants from Ricaurte, accounting for 78% of total population. Results:: A high prevalence of carriers of the expanded allele was observed in all FXS mutation categories. Using the Bayesian methods the carrier frequency of FM was 48.2 (95% Credibility Region CR: 36.3–61.5) per 1000 males and 20.5 (95% CR:13.5–28.6) per 1000 females; the frequency of premutation carrier was 14.1 (95% RC: 8.0–21.7) per 1000 males (95% RC: 8.0–21.7 per 1000 males) and 35.9 (95% RC: 26.5–46.2) per 1000 for females (95% RC: 26.5–46.2 per 1000 females), and gray zone carrier was 13.4 (95% RC: 7.4–20.7) per 1000 males (95% RC: 7.4–20.7 per 1000 males) and 42.2 (95% RC: 32.2–53.8) per 1000 for females (95% RC: 32.2–53.8 per 1000 females). Differences in carrier frequencies were observed for premutation and FM alleles between natives and non-natives. Conclusions:: This study shows that in Ricaurte the carrier frequencies of FMR1 expanded alleles (premutations and FMs) are higher than those reported in the literature, suggesting that Ricaurte constitutes a genetic cluster of FXS.

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