ATRX mutation in two adult brothers with non-specific moderate intellectual disability identified by exome sequencing
Open accessAbstract
In this report, we describe two adult brothers affected by moderate non-specific intellectual disability (ID). They showed minor facial anomalies, not clearly ascribable to any specific syndromic patterns, microcephaly, brachydactyly and broad toes. Both brothers presented seizures. Karyotype, subtelomeric and FMR1 analysis were normal in both cases. We performed array-CGH analysis that revealed no copy-number variations potentially associated with ID. Subsequent exome sequence analysis allowed the identification of the ATRX c.109C>T (p.R37X) mutation in both the affected brothers. Sanger sequencing confirmed the presence of the mutation in the brothers and showed that the mother is a healthy carrier. Mutations in the ATRX gene cause the X-linked alpha thalassemia/mental retardation (ATR-X) syndrome (MIM #301040), a severe clinical condition usually associated with profound ID, facial dysmorphism and alpha thalassemia. However, the syndrome is clinically heterogeneous and some mutations, including the c.109C>T, are associated with a broad phenotypic spectrum, with patients displaying a less severe phenotype with only mild-moderate ID. In the case presented here, exome sequencing provided an effective strategy to achieve the molecular diagnosis of ATR-X syndrome, which otherwise would have been difficult to consider due to the mild non-specific phenotype and the absence of a family history with typical severe cases.
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Mutations in the HHMC-carrying gene encoding for the transcription factor ATRX cause facial dysmorphism.
“mutations in the HHMC-carrying gene encoding for the transcription factor ATRX cause facial dysmorphism138.”
From A catalog of single nucleotide changes distinguishing modern humans from archaic hominins (2019) · cites this paper as [138]
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A catalog of single nucleotide changes distinguishing modern humans from archaic hominins
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- Authors
- Moncini, S., Bedeschi, M. F., Castronovo, P., Crippa, M., Calvello, M., Garghentino, R. R., Scuvera, G., Finelli, P., & Venturin, M.
- Affiliations
- University of Milan (IT)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- IRCCS Istituto Auxologico Italiano (IT)
- IRCCS Eugenio Medea (IT)
- Corresponding author
- Venturin, M.
- Venue
- Meta Gene
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 1
- Pages
- 102-108
- ISSN
- 2214-5400 (ISSN-L)
- PMC
- PMC4205036
- OpenAlex
- W2019599574
- Cited by
- 10
- References
- 15
- Citations by year
- 2025: 1 · 2024: 2 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 2
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Meta Gene (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, cc-by-nc-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- ATRX mutation, ATR-X syndrome, X-linked intellectual disability, alpha-thalassemia, seizures, microcephaly, brachydactyly, facial anomalies, phenotypic heterogeneity, molecular diagnosis, exome sequencing
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