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. 2014 Oct 29:15:116.
doi: 10.1186/s12881-014-0116-3.

Familial imbalance in 16p13.11 leads to a dosage compensation rearrangement in an unaffected carrier

Alicia Delicado  1   2 , Luis Fernández  3   4 , María Luisa de Torres  5   6 , Julián Nevado  7   8 , Fe Amalia García-Santiago  9   10 , Roberto Rodríguez  11 , Elena Mansilla  12   13 , María Palomares  14   15 , Fernando Santos-Simarro  16   17 , Elena Vallespín  18   19 , María Ángeles Mori  20   21 , Pablo Lapunzina  22   23
Affiliations

Familial imbalance in 16p13.11 leads to a dosage compensation rearrangement in an unaffected carrier

Alicia Delicado et al. BMC Med Genet. .

Abstract

Background: We and others have previously reported that familial cytogenetic studies in apparently de novo genomic imbalances may reveal complex or uncommon inheritance mechanisms.

Methods: A familial, combined genomic and cytogenetic approach was systematically applied to the parents of all patients with unbalanced genome copy number changes.

Results: Discordant array-CGH and FISH results in the mother of a child with a prenatally detected 16p13.11 interstitial microduplication disclosed a balanced uncommon rearrangement in this chromosomal region. Further dosage and haplotype familial studies revealed that both the maternal grandfather and uncle had also the same 16p duplication as the proband. Genomic compensation observed in the mother probably occurred as a consequence of interchromosomal postzygotic nonallelic homologous recombination.

Conclusions: We emphasize that such a dualistic strategy is essential for the full characterization of genomic rearrangements as well as for appropriate genetic counseling.

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Figures

Figure 1
Figure 1
aCGH and FISH results in the proband and the mother. a) Proband aCGH results showing 16p13.11 duplication. b-c) Proband FISH results with probe NDE1-MYH11 (red) showing two signals on the metaphase chromosomes (b) and three signals on the interphase nucleus (c). d) Mother aCGH results showing no 16p13.11 duplication. e-f) Mother FISH results with the same probe showing one signal on metaphase chromosomes (e) and two signals on the interphase nucleus (f).
Figure 2
Figure 2
Pedigree chart showing haplotypes of 12 markers spanning chromosome 16. Markers D16S3060, D16S3127 and D16S405 are located within the rearranged segment 16p13.11, which shows extra dosage in individuals I:1, II:1, II:3, III:1 and III:2. Colors indicate the grandparental origin of the chromosomal material. Numbers designate the size in bp of the fragment including the marker.
Figure 3
Figure 3
Postzygotic hypothesis for the rearrangement in chromosome 16 leading to genomic compensation in the mother (II:3). Mitotic recombination between a paternal chromatid carrying the duplication and a normal maternal chromatid during the first zygotic divisions would originate four different chromatids, two of which would be selected in a compensated genotype. Circles indicate region 16p13.11, which is colored as in Figure 2. P and M designate the paternal and maternal chromosome, respectively.
See this image and copyright information in PMC

References

    1. Carelle-Calmels N, Saugier-Veber P, Girard-Lemaire F, Rudolf G, Doray B, Guérin E, Kuhn P, Arrivé M, Gilch C, Schmitt E, Fehrenbach S, Schnebelen A, Frébourg T, Flori E. Genetic compensation in a human genomic disorder. N Engl J Med. 2009;360(12):1211–1216. doi: 10.1056/NEJMoa0806544. - DOI - PubMed
    1. Alkalay AA, Guo T, Montagna C, Digilio MC, Dallapiccola B, Marino B, Morrow B. Genetic dosage compensation in a family with velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome. Am J Med Genet A. 2011;155A(3):548–554. doi: 10.1002/ajmg.a.33861. - DOI - PMC - PubMed
    1. Fernández L, Nevado J, De Torres ML, Mansilla E, Vallespín E, García-Miñaúr S, Palomo R, Deirós L, Cabrera M, Galo ED, Lapunzina P, Delicado A. Additional case of an uncommon 22q11.2 reciprocal rearrangement in a phenotypically normal mother of children with 22q11.2 deletion and 22q11.2 duplication syndromes. Am J Med Genet A. 2012;158A(11):2963–2968. doi: 10.1002/ajmg.a.35595. - DOI - PubMed
    1. Nowakowska BA, de Leeuw N, Ruivenkamp CA, Sikkema-Raddatz B, Crolla JA, Thoelen R, Koopmans M, den Hollander N, van Haeringen A, van der Kevie-Kersemaekers AM, Pfundt R, Mieloo H, van Essen T, de Vries BB, Green A, Reardon W, Fryns JP, Vermeesch JR. Parental insertional balanced translocations are an important cause of apparently de novo CNVs in patients with developmental anomalies. Eur J Hum Genet. 2012;20(2):166–170. doi: 10.1038/ejhg.2011.157. - DOI - PMC - PubMed
    1. Hannes FD, Sharp AJ, Mefford HC, de Ravel T, Ruivenkamp CA, Breuning MH, Fryns JP, Devriendt K, Van Buggenhout G, Vogels A, Stewart H, Hennekam RC, Cooper GM, Regan R, Knight SJ, Eichler EE, Vermeesch JR. Recurrent reciprocal deletions and duplications of 16p13.11: the deletion is a risk factor for MR/MCA while the duplication may be a rare benign variant. J Med Genet. 2009;46(4):223–232. doi: 10.1136/jmg.2007.055202. - DOI - PMC - PubMed

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