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Open Access 09-07-2022 | Intrauterine Growth Restriction | Original Article

Pathogenic correlation between mosaic variegated aneuploidy 1 (MVA1) and a novel BUB1B variant: a reappraisal of a severe syndrome

Authors: Piero Pavone, Xena Giada Pappalardo, Naira Mustafa, Raffaele Falsaperla, Simona Domenica Marino, Giovanni Corsello, Sebastiano Bianca, Enrico Parano, Martino Ruggieri

Published in: Neurological Sciences | Issue 11/2022

Abstract

Background

The BUB 1 mitotic checkpoint serine/threonine kinase B (BUB1B) gene encodes a key protein in the mitotic spindle checkpoint, which acts as a surveillance mechanism, crucial for the maintenance of the correct chromosome number during cell deviation. Mutations of BUB1B gene are linked to mosaic variegated aneuploidy 1 (MVA1) syndrome, a rare autosomal recessive disorder characterized by widespread mosaic aneuploidies, involving different chromosomes and tissues. MVA1 is clinically characterized by intrauterine growth restriction, post-natal growth retardation, and severe neurologic impairment including microcephaly, developmental delay/intellectual disability, epileptic seizures, and generalized hypotonia. Malignancies are also serious sequelae associated with the disorder. We reported on a case of two-year-old Italian girl with MVA1 who shows severe neurologic impairment, microcephaly and epileptic seizures.

Materials and methods

Clinical data collection and genetic diagnosis of the patient were assessed. Mutational analysis covers the chromosomal microarray analysis, the gene methylation pattern studied using the methylation-specific multiplex ligation-dependent probe amplification, and the family-based Whole Exome Sequencing (WES). A literature research based on reported cases of MVA and premature chromatid separation was also included.

Results

Karyotyping has revealed 12% of mosaics in the patient who carries a novel variant in BUB1B gene (c.2679A > T, p.Arg893Ser) detected by WES. Thirty-one cases of MVA1 including the present report, and four prenatally diagnosed cases with MVA1 were selected and inspected.

Conclusion

Clinical and genetic findings reported in the girl strongly suggest a new MVA1 genotype–phenotype correlation and lead to a reappraisal of a severe syndrome. Diagnosis and in-depth follow-up provided worthwhile data.

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Title: Pathogenic correlation between mosaic variegated aneuploidy 1 (MVA1) and a novel BUB1B variant: a reappraisal of a severe syndrome
Authors: Piero Pavone
Xena Giada Pappalardo
Naira Mustafa
Raffaele Falsaperla
Simona Domenica Marino
Giovanni Corsello
Sebastiano Bianca
Enrico Parano
Martino Ruggieri
Publication date: 09-07-2022
Publisher: Springer International Publishing
Keywords: Intrauterine Growth Restriction
Epileptic Seizure
Published in: Neurological Sciences / Issue 11/2022
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-022-06247-w

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Pathogenic correlation between mosaic variegated aneuploidy 1 (MVA1) and a novel BUB1B variant: a reappraisal of a severe syndrome

Abstract

Background

Materials and methods

Results

Conclusion

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