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
. 2020 Feb;8(2):e957.
doi: 10.1002/mgg3.957. Epub 2019 Sep 30.

Breakpoint delineation in 5p- patients leads to new insights about microcephaly and the typical high-pitched cry

Samar N Chehimi  1   2 , Évelin A Zanardo  1 , José R M Ceroni  2 , Amom M Nascimento  1 , Fabrícia A R Madia  1 , Alexandre T Dias  1 , Gil M N Filho  1 , Marília M Montenegro  1 , Jullian Damasceno  1 , Thaís V M M Costa  1 , Yanca Gasparini  1 , Chong A Kim  2 , Leslie D Kulikowski  1   2
Affiliations

Breakpoint delineation in 5p- patients leads to new insights about microcephaly and the typical high-pitched cry

Samar N Chehimi et al. Mol Genet Genomic Med. 2020 Feb.

Abstract

Background: Cri du chat syndrome (CdCS) is a rare syndrome caused by a partial or complete deletion of the short arm of chromosome 5 (5p-). The main clinical features include a high-pitched cry, facial asymmetry, microcephaly, round face at birth, epicanthal folds, hypotonia, delayed growth and development.

Methods: We studied 14 Brazilian patients with CdCS using genomic array in order to better define the 5p breakpoints and recognize copy number variations (CNVs) that contribute to clinical manifestations associated with the syndrome.

Results: Array confirmed terminal deletions in 13 patients and an interstitial deletion in one patient. It was also possible to map the breakpoints and associate a genomic region of 4.7 Mb to the development of head circumference and cat-like cry. We also found other CNVs concomitant to the 5p deletion including a 9p duplication, a 17q deletion, and a 22q deletion in three different patients.

Conclusion: With advancements of molecular cytogenomic methods in the last two decades, it was possible to evidence cryptic alterations and improve the genotype-phenotype correlation. In this work, we describe a new genomic region associated with microcephaly and cat-like cry and highlight the importance of precise delineation of 5p deletion breakpoints and detection of other CNVs in CdCS patients to improve genotype-phenotype correlation to perform a complete clinical and molecular diagnosis.

Keywords: Brazilian patients; cri du chat; cytogenomic; genomic array.

PubMed Disclaimer

Conflict of interest statement

There are no conflict of interest to disclose.

Figures

Figure 1
Figure 1
Head circumference in females and males with CdCS from birth to 15 years. Normal growth curves (N) are represented by the grey area and CdCS specific curves are indicated by the thick black lines. The results found in our 10 patients (red circles) showed that only one patient (patient 14) appears to have no microcephaly (red arrow) with measurements between 2nd < p < 50th for normal growth curves and 98th for CdCS’ growth curves. Adapted from Marinescu et al. (2000). CdCS, cri du chat syndrome
Figure 2
Figure 2
Representation of the deletions extent, indicated by the horizontal purple bars, and breakpoints in basepairs detected through array. TERT, SEMA5A, MARCH6, CTNND2, and NPR3 are marked with dotted lines. At the bottom are presented the genotype–phenotype relationships from data in previous publications. The genomic region we propose to be associated with head circumference and cat‐like cry is indicated in the orange box. p, short arm; q, long arm; bp, base pairs
See this image and copyright information in PMC

References

    1. Ballif, B. C. , Wakui, K. , Gajecka, M. , & Shaffer, L. G. (2004). Translocation breakpoint mapping and sequence analysis in three monosomy 1p36 subjects with der(1)t(1;1)(p36;q44) suggest mechanisms for telomere capture in stabilizing de novo terminal rearrangements. Human Genetics, 114(2), 198–206. 10.1007/s00439-003-1029-y - DOI - PubMed
    1. Duan, Y. , Wang, S. H. , Song, J. , Mironova, Y. , Ming, G. L. , Kolodkin, A. L. , & Giger, R. J. (2014). Semaphorin 5A inhibits synaptogenesis in early postnatal‐ and adult‐born hippocampal dentate granule cells. Elife, 3, 1–24. 10.7554/eLife.04390 - DOI - PMC - PubMed
    1. Elmakky, A. , Carli, D. , Lugli, L. , Torelli, P. , Guidi, B. , Falcinelli, C. , … Percesepe, A. (2014). A three‐generation family with terminal microdeletion involving 5p15.33‐32 due to a whole‐arm 5;15 chromosomal translocation with a steady phenotype of atypical cri du chat syndrome. European Journal of Medical Genetics, 57(4), 145–150. 10.1016/j.ejmg.2014.02.005 - DOI - PubMed
    1. Gersh, M. , Goodart, S. A. , Pasztor, L. M. , Harris, D. J. , Weiss, L. , & Overhauser, J. (1995). Evidence for a distinct region causing a cat‐like cry in patients with 5p deletions. American Journal of Human Genetics, 56(6), 1404–1410. - PMC - PubMed
    1. Kearney, H. M. , Thorland, E. C. , Brown, K. K. , Quintero‐Rivera, F. , & South, S. T. ; Working Group of the American College of Medical Genetics Laboratory Quality Assurance Committee . (2011). American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genetics in Medicine, 13(7), 680–685. 10.1097/GIM.0b013e3182217a3a - DOI - PubMed

Publication types

LinkOut - more resources