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Deletions in the 3' part of the NFIX gene including a recurrent Alu-mediated deletion of exon 6 and 7 account for previously unexplained cases of Marshall-Smith syndrome

Schanze D, Neubauer D, Cormier-Daire V, Delrue MA, Dieux-Coeslier A, Hasegawa T, Holmberg EE, Koenig R, Krueger G, Schanze I, Seemanova E, Shaw AC, Vogt J, Volleth M, Reis A, Meinecke P, Hennekam RCM, Zenker M (2014)

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Publication Type: Journal article

Publication year: 2014

Journal

Book Volume: 35

Pages Range: 1092-100

Journal Issue: 9

DOI: 10.1002/humu.22603

Abstract

Marshall-Smith syndrome (MSS) is a very rare malformation syndrome characterized by typical craniofacial anomalies, abnormal osseous maturation, developmental delay, failure to thrive, and respiratory difficulties. Mutations in the nuclear factor 1/X gene (NFIX) were recently identified as the cause of MSS. In our study cohort of 17 patients with a clinical diagnosis of MSS, conventional sequencing of NFIX revealed frameshift and splice-site mutations in 10 individuals. Using multiplex ligation-dependent probe amplification analysis, we identified a recurrent deletion of NFIX exon 6 and 7 in five individuals. We demonstrate this recurrent deletion is the product of a recombination between AluY elements located in intron 5 and 7. Two other patients had smaller deletions affecting exon 6. These findings show that MSS is a genetically homogeneous Mendelian disorder. RT-PCR experiments with newly identified NFIX mutations including the recurrent exon 6 and 7 deletion confirmed previous findings indicating that MSS-associated mutant mRNAs are not cleared by nonsense-mediated mRNA decay. Predicted MSS-associated mutant NFIX proteins consistently have a preserved DNA binding and dimerization domain, whereas they grossly vary in their C-terminal portion. This is in line with the hypothesis that MSS-associated mutations encode dysfunctional proteins that act in a dominant negative manner.

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APA:

Schanze, D., Neubauer, D., Cormier-Daire, V., Delrue, M.-A., Dieux-Coeslier, A., Hasegawa, T.,... Zenker, M. (2014). Deletions in the 3' part of the NFIX gene including a recurrent Alu-mediated deletion of exon 6 and 7 account for previously unexplained cases of Marshall-Smith syndrome. Human Mutation, 35(9), 1092-100. https://doi.org/10.1002/humu.22603

MLA:

Schanze, Denny, et al. "Deletions in the 3' part of the NFIX gene including a recurrent Alu-mediated deletion of exon 6 and 7 account for previously unexplained cases of Marshall-Smith syndrome." Human Mutation 35.9 (2014): 1092-100.

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