Abstract
Interstitial 6p25.1p24.3 microdeletions are rare events and a clear karyotype/phenotype correlation has not yet been determined. In this study, we present the clinical and molecular description of a child with a de novo 6p25.1p24.3 microdeletion, characterized by array-CGH, associated with mild intellectual disability, facial dysmorphisms, hypopigmentation of the skin of the abdomen, heart defects, mild pontine hypoplasia and hypotonia. This deleted region contains 14 OMIM genes (NRN1, F13A1, RREB1, SSR1, RIOK1, DSP, BMP6, TXNDC5, BLOC1S5, EEF1E1, SLC35B3 and HULC). To the best of our knowledge until now only six cases have been reported presenting an interstitial microdeletion, but a unique case carries a deleted region containing the same genes of our patient. We compared clinical features and genetic data with that of the previously reported patient. We also analysed the gene content of the deleted region to investigate the possible role of specific genes in the clinical phenotype of our patient.
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Andriopoulos B., Corradini E., Xia Y., Faasse S. A., Chen S., Grgurevic L. et al. 2009 BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nat. Genet. 41, 482–487.
An K., Jung J. H., Jeong A. Y., Kim H. G., Jung S. Y., Lee K. et al. 2014 Neuritin can normalize neural deficits of Alzheimer’s disease. Cell Death Dis. 5, e1523.
Boone P. M., Bacino C. A., Shaw C. A., Eng P. A., Hixson P. M., Pursley A. N. et al. 2010 Detection of clinically relevant exonic copy-number changes by array CGH. Hum. Mutat. 31, 1326–1342.
Bravo R., Parra V., Gatica D., Rodriguez A. E., Torrealba N., Paredes F. et al. 2013 Chapter five - Endoplasmic reticulum and the unfolded protein response: dynamics and metabolic integration. Int. Rev. Cell Mol. Biol. 301, 215–290.
Davies A. F., Mirza G., Flinter F. and Ragoussis J. 1999 An interstitial deletion of 6p24-p25 proximal to the FKHL7 locus and including AP-2alpha that affects anterior eye chamber development. J. Med. Genet. 36, 708–710.
DeScipio C. 2007 The 6p subtelomere deletion syndrome. Am. J. Med. Genet. C. Semin. Med. Genet. 145C, 377–382.
Farley J. E., Burdett T. C., Barria R., Neukomm L. J., Kenna K. P., Landers J. E. et al. 2018 Transcription factor Pebbled/RREB1 regulates injury-induced axon degeneration. Proc. Natl. Acad. Sci. USA 115, 1358–1363.
Fujino T., Wu Z., Lin W. C., Phillips M. A. and Nedivi E. 2008 cpg15 and cpg15-2 constitute a family of activity-regulated ligands expressed differentially in the nervous system to promote neurite growth and neuronal survival. J. Comp. Neurol. 507, 1831–1845.
Karamoysoyli E., Burnand R. C., Tomlinson D. R. and Gardiner N. J. 2008 Neuritin mediates Nerve Growth Factor–induced axonal regeneration and is deficient in experimental diabetic neuropathy. Diabetes 57, 181–189.
Kautz L., Meynard D., Monnier A., Darnaud V., Bouvet R. and Wang R. H. 2008 Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6, Smad 7, Id1, and Atoh8 in the mouse liver. Blood 112, 1503–1509.
Kuipers B. C., Vulto-van Silfhout A. and T., Marcelis C., Pfundt R., de Leeuw N. and de Vries B. B. 2013 Two patients with intellectual disability, overlapping facial features, and overlapping deletions in 6p25.1p24.3. Clin. Dysmorphol. 22, 18–21.
Larimore J., Zlatic S. A., Gokhale A., Tornieri K., Singleton K. S., Mullin A. P. et al. 2014 Mutations in the BLOC-1 subunits dysbindin and muted generate divergent and dosage dependent phenotypes. J. Biol. Chem. 289, 14291–14300.
Linhares N. D., Svartman M., Rodrigues T. C., Rosenberg C. and Valadares E. R. 2015 Subtelomeric 6p25 deletion/duplication: Report of a patient with new clinical findings and genotype-phenotype correlations. Eur. J. Med. Genet. 58, 310–318.
Meynard D., Kautz L., Darnaud V., Canonne-Hergaux F., Coppin H. and Roth M. P. 2009 Lack of the bone morphogenetic protein BMP6 induces massive iron overload. Nat. Genet. 41, 478–481.
Mirza G., Williams R. R., Mohammed S., Clark R., Newbury-Ecob R., Baldinger S. et al. 2004 Refined genotype-phenotype correlations in cases of chromosome 6p deletion syndromes. Eur. J. Hum. Genet. 12, 718–728.
Putz U., Harwell C. and Nedivi E. 2005 Soluble CPG15 expressed during early development rescues cortical progenitors from apoptosis. Nat. Neurosci. 8, 322–333.
Qi Z., Jeng L. J., Slavotinek A. and Yu J. 2015 Haploinsufficiency and triploinsensitivity of the same 6p25.1p24.3 region in a family. BMC Med. Genomics 8, 38.
Rossberg W., Saternus R., Wagenpfeil S., Kleber M., März W., Reichrath S. et al. 2016 Human pigmentation, cutaneous vitamin D synthesis and evolution: variants of genes (SNPs) involved in skin pigmentation are associated with 25(OH)D serum concentration. Anticancer Res. 36, 1429–1437.
Acknowledgements
This work was supported by ‘Cinque per mille dell’IRPEF-Finanziamento della ricerca sanitaria’ and ‘Finanziamento Ricerca Corrente’, Ministero Salute (contributo per la ricerca intramurale).
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Tassano, E., Uccella, S., Severino, M. et al. Expanding the phenotype associated with interstitial 6p25.1p24.3 microdeletion: a new case and review of the literature. J Genet 100, 9 (2021). https://doi.org/10.1007/s12041-021-01261-x
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DOI: https://doi.org/10.1007/s12041-021-01261-x