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Hyperphagia, mild developmental delay but apparently no structural brain anomalies in a boy without SOX3 expression.
Johan Robert Helle1, Tuva Barøy, Doriana Misceo
1Faculty of Medicine, Department of Medical Genetics, University of Oslo, Blindern, Oslo, Norway.
American Journal of Medical Genetics. Part A
|March 7, 2013
Summary
A small deletion of the SOX3 gene in a boy caused mild intellectual disability and developmental delays. Genetic redundancy likely compensated for SOX3 loss, preserving brain structure despite the mutation.
Area of Science:
- Genetics
- Developmental Biology
- Neuroscience
Background:
- SOX3 is crucial for early vertebrate brain, pituitary, and craniofacial development.
- SOX3 gene mutations, including duplications and expansions, are linked to intellectual disability and hypopituitarism in humans.
- Sox3 knockout mice exhibit developmental anomalies in branchial arches and midline brain structures.
Observation:
- We present an 8-year-old male with a 2.1 Mb deletion in Xq27.1q27.2, encompassing the entire SOX3 gene, inherited from his mother.
- This represents the smallest reported deletion including the complete SOX3 gene in a male.
- The patient displays mild intellectual disability, language delay, dysarthria, behavioral issues, minor facial anomalies, and hyperphagia, but has normal hormone levels and no apparent brain structural abnormalities on MRI.
Findings:
- Despite the complete absence of SOX3, the patient's brain structures appear normal on MRI.
- The observed phenotype is milder than expected for SOX3 nullisomy, suggesting compensatory mechanisms.
- Hormonal axes, including the hypothalamo-pituitary axis, are functioning normally.
Implications:
- Genetic redundancy among SOX family proteins may play a significant role in early human brain development.
- This case highlights the complex genotype-phenotype correlations in SOX3-related disorders.
- Understanding SOX gene family interactions is crucial for diagnosing and managing neurodevelopmental disorders.
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