Background: Chromosome 1p31 deletion (OMIM #613735) involving the NFIA gene (OMIM 600727) is characterised by variable defects in the formation of the corpus callosum, craniofacial abnormalities and urinary tract defects. A review of current literature suggests only seven cases have been reported, none of which had an isolated NFIA gene defect.
Methods: We submit the clinical and molecular features of an 8-year-old female patient with a microdeletion of chromosome 1p31.3 who has developmental delay, metopic synostosis and macroscopic haemoglobinuria. She was investigated with karyotyping, subtelomeric FISH and microarray CGH.
Results: Array CGH identified a single 120 kb microdeletion of 1p31.3 involving exons 4-9 of the NFIA gene. Her brain MRI showed hypoplasia of the corpus callosum especially in the posterior areas. Karyotype was normal, ruling out structural chromosomal abnormalities.
Conclusion: In this study, we confirmed that a microdeletion in the chromosome region 1p31.3 involving the NFIA gene is associated with hypoplasia of the corpus callosum, developmental delay, metopic synostosis and urinary tract abnormalities. Furthermore, we propose a mechanism by which disruptions in the NFIA gene causes craniofacial abnormalities. This report presents the first case of an intragenic deletion within the NFIA gene that is still consistent with classic clinical phenotypes present in previously reported cases of chromosome 1p31.3 related deletion. This finding will help clarify the role of the NFIA gene in the normal formation of parts of the CNS, the craniofacial complex and the urinary tract.
Keywords: Chromosome 1p31.3; Corpus callosum agenesis; Craniofacial defects; Microdeletion; NFIA gene.
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