Intragenic MBD5 familial deletion variant does not negatively impact MBD5 mRNA expression

Area of Science:

• Genetics
• Molecular Biology
• Neurology

Background:

• 2q23.1 deletion syndrome presents with intellectual disability, speech impairment, seizures, sleep disturbances, behavioral issues, and hypotonia.
• Haploinsufficiency of the MBD5 gene is the primary cause of the core features associated with 2q23.1 deletion syndrome.
• Deletions involving coding and noncoding exons of MBD5 typically lead to reduced MBD5 mRNA expression.

Purpose of the Study:

• To investigate a patient exhibiting a neurological and behavioral phenotype resembling 2q23.1 deletion syndrome.
• To determine the pathogenicity of an inherited intronic deletion in the 5-prime untranslated region of the MBD5 gene in this patient.

Main Methods:

• Clinical evaluation of a patient with a neurological and behavioral phenotype.
• Genetic analysis to identify an inherited intronic deletion in the 5-prime untranslated region of MBD5.
• Quantitative assessment of MBD5 mRNA expression levels.

Main Results:

• The patient presented with a phenotype similar to 2q23.1 deletion syndrome.
• An inherited intronic deletion in the 5-prime untranslated region of MBD5 was identified.
• MBD5 mRNA expression levels in the patient were found to be normal, indicating the deletion is likely not causative.

Conclusions:

• The identified intronic deletion in MBD5 is unlikely to be the cause of the patient's 2q23.1 deletion syndrome-like phenotype.
• It is crucial to validate the pathogenicity of intronic deletions, particularly those in untranslated regions, when assessing genetic disorders.
• This case highlights the importance of correlating genetic findings with molecular data like mRNA expression for accurate diagnosis.