Novel heterozygous mutation in TBX1 in an infant with hypocalcemic seizures

Area of Science:

• Genetics
• Pediatrics
• Developmental Biology

Background:

• 22q11.2 deletion syndrome is characterized by specific facial features, palate issues, hypoparathyroidism, thymic hypoplasia, and heart defects.
• The TBX1 gene, located in the 22q11.2 region, is implicated in this syndrome, with mutations found in some patients lacking the deletion.

Purpose of the Study:

• To investigate the role of TBX1 mutations in infants presenting with hypocalcemia and thymic hypoplasia but without 22q11.2 deletion.
• To explore genotype-phenotype correlations in TBX1-related disorders.

Main Methods:

• Case report of an infant with hypocalcemic seizures and thymic hypoplasia.
• Genetic analysis including G-banding, fluorescent in situ hybridization (FISH), and TBX1 gene sequencing.
• Clinical evaluation for characteristic 22q11.2 deletion syndrome features.

Main Results:

• A novel heterozygous TBX1 mutation was identified in the infant.
• The infant presented with hypocalcemic seizures and thymic hypoplasia but lacked typical facial features, palate abnormalities, and cardiac anomalies of 22q11.2 deletion syndrome.
• Tbx1 transgenic mouse studies previously linked TBX1 to 22q11.2 deletion syndrome.

Conclusions:

• Thymic hypoplasia in hypocalcemic infants lacking 22q11.2 deletion should prompt investigation for TBX1 mutations.
• This case highlights the phenotypic variability associated with TBX1 mutations and expands the spectrum of conditions linked to this gene.