Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2019 Jun 14:12:26.
doi: 10.1186/s13039-019-0440-6. eCollection 2019.

A familial chromosomal complex rearrangement confirms RUNX1T1 as a causative gene for intellectual disability and suggests that 1p22.1p21.3 duplication is likely benign

Fabrizia Restaldi  1 , Viola Alesi  1 , Angela Aquilani  1 , Silvia Genovese  1 , Serena Russo  1 , Valentina Coletti  1 , Daniele Pompili  1 , Roberto Falasca  1 , Bruno Dallapiccola  1 , Rossella Capolino  1 , Matteo Luciani  1 , Antonio Novelli  1
Affiliations
Case Reports

A familial chromosomal complex rearrangement confirms RUNX1T1 as a causative gene for intellectual disability and suggests that 1p22.1p21.3 duplication is likely benign

Fabrizia Restaldi et al. Mol Cytogenet. .

Abstract

Background: Complex chromosomal rearrangements are constitutive structural aberrations involving three or more breaks. They can be balanced or unbalanced and result in different outcomes, depending on deletion/duplication of genomic material, gene disruption, or position effects.

Case presentation: We report on a patient presenting with severe anemia, splenomegaly, mild intellectual disability and facial dysmorphisms harboring a 4.3 Mb duplication at 1p22.1p21.3 and a 2.1 Mb deletion at 8q21.3q22.1, involving RUNX1T1 gene. The healthy brother presented the same duplication of chromosome 1p as at 1p22.1p21.3.

Conclusions: The rearrangement found both these siblings resulted from malsegregation in the proband and recombination in her healthy brother of a balanced paternal complex chromosomal rearrangement. These results confirm RUNX1T1 as a causative gene for intellectual disability and suggest the 1p22.1p21.3 duplication is likely benign.

Keywords: 1p22.1p21.3 duplication; 8q21.3q22.1 deletion; Complex chromosomal rearrangements; RUNX1T1.

PubMed Disclaimer

Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Patient at 3 years old. Note dysmorphic facial features (blepharophimosis, ocular hypertelorism, long philtrum and abnormal ear configuration
Fig. 2
Fig. 2
segregation analysis
Fig. 3
Fig. 3
FISH analysis of metaphases from patient (a), her father (b) and her brother (c)
See this image and copyright information in PMC

References

    1. Liao Y, Wang L, Zhang D, Liu C. Identification of a balanced complex chromosomal rearrangement involving chromosomes 3, 18 and 21 with recurrent abortion: case report. Mol Cytogenet. 2014;7:39. doi: 10.1186/1755-8166-7-39. - DOI - PMC - PubMed
    1. Durmaz CD, Yararbaş K, Kutlay NY, Türedi Ö, Akın İ, Gürbüz C, Karataş G. Tükün. A Unusual Chromosomal Rearrangement Resulted in Interstitial Monosomy 9p: Case Report. Cytogenet Genome Res. 2016;148(1):19–24. doi: 10.1159/000444872. - DOI - PubMed
    1. Gardner RJM, Sutherland GR, Lisa G. Shaffer, chromosome abnormalities and genetic counselling. UK: Oxford University Press; 2012.
    1. Alesi V, Orlando V, Genovese S, Loddo S, Pisaneschi E, Pompili D, Surace C, Restaldi F, Digilio MC, Dallapiccola B, Dentici ML, Novelli A. Interstitial 10q21.1q23.31 Duplication due to Meiotic Recombination of a Paternal Balanced Complex Rearrangement: Cytogenetic and Molecular Characterization. Cytogenet Genome Res. 2017;151(4):179–185. doi: 10.1159/000475490. - DOI - PubMed
    1. Valli R, Vinti L, Frattini A, Fabbri M, Montalbano G, Olivieri C, Minelli A, Locatelli F, Pasquali F, Maserati E. Bone marrow failure may be caused by chromosome anomalies exerting effects on RUNX1T1 gene. Mol Cytogenet. 2018;11:2. doi: 10.1186/s13039-017-0352-2. - DOI - PMC - PubMed

Publication types

LinkOut - more resources