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A female with typical fragile-X phenotype caused by maternal isodisomy of the entire X chromosome

Journal of Human Genetics volume 65, pages 551–555 (2020)Cite this article

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Abstract

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability, especially in males. Females with FXS tend to be relatively mildly affected because of compensation by a second X chromosome with a normal FMR1 gene. In most cases, FXS is caused by an expansion of the CGG repeats (>200 triplets, full mutation, FM) in the 5′-untranslated region of the FMR1 gene. Premutation alleles (PM, 55–200 repeats), usually lack the clinical features of FXS, are highly unstable when transmitted to offspring and can give rise to FM, especially in female meiosis. We describe a 3-year-old girl with typical FXS, with only a fully expanded FMR1 allele (288 CGG repeats) due to uniparental isodisomy of X chromosome, inherited from mother carrying a premutation allele. The patient’s FMR1 methylation region is completely methylated due to full mutation of CGG repeat. This unusual and rare case indicates the importance of a detailed genomic approach to explain nontraditional Mendelian inheritance pattern.

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Authors and Affiliations

  1. Department of Pediatrics, Daegu Catholic University School of Medicine, Daegu, South Korea

    Jin-Kyung Kim & Ji-Eun Jeong

  2. Department of Laboratory Medicine, Green Cross Genome, Yong-in, South Korea

    Jong-Moon Choi

  3. Department of Pediatrics & Medical Genetics, Asan Medical, Center University of Ulsan College of Medicine, Seoul, South Korea

    Gu-Hwan Kim & Han-Wook Yoo

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  1. Jin-Kyung Kim
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  2. Ji-Eun Jeong
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  3. Jong-Moon Choi
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  4. Gu-Hwan Kim
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Correspondence to Han-Wook Yoo.

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Kim, JK., Jeong, JE., Choi, JM. et al. A female with typical fragile-X phenotype caused by maternal isodisomy of the entire X chromosome. J Hum Genet 65, 551–555 (2020). https://doi.org/10.1038/s10038-020-0735-9

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  • DOI: https://doi.org/10.1038/s10038-020-0735-9

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