Refining the Phenotype of Recurrent Rearrangements of Chromosome 16

International Journal of Molecular Sciences

Luigina Spaccini¹  Silvia Maitz²  Angelo Selicorni³  Miriam Rigoldi⁴  Nicoletta Villa⁴  Francesca Crosti⁴  Elena Sala⁴  Serena Redaelli⁵  Gaia Roversi⁵  Angela Bentivegna⁵  Donatella Conconi⁵  Leda Dalprà⁵ 

[1] Clinical Genetics Unit, Department of Obstetrics and Gynecology, V. Buzzi Children’s Hospital, University of Milan, 20154 Milan, Italy;Clinical Pediatric Genetics Unit, Pediatrics Clinics, MBBM Foundation, S. Gerardo Hospital, 20900 Monza, Italy;Clinical Pediatric Unit, ASST Lariana, 22042 Como, Italy;Medical Genetics Laboratory, Clinical Pathology Department, S. Gerardo Hospital, 20900 Monza, Italy;School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy;

关键词: chromosome 16;    array-CGH;    CNV;    developmental disability;    speech disorder;    two-hit model;    16p13.11 deletions and duplications;    16p11.2 deletions and duplications;   

DOI  :  10.3390/ijms20051095

来源: DOAJ

【 摘 要 】

Chromosome 16 is one of the most gene-rich chromosomes of our genome, and 10% of its sequence consists of segmental duplications, which give instability and predisposition to rearrangement by the recurrent mechanism of non-allelic homologous recombination. Microarray technologies have allowed for the analysis of copy number variations (CNVs) that can contribute to the risk of developing complex diseases. By array comparative genomic hybridization (CGH) screening of 1476 patients, we detected 27 cases with CNVs on chromosome 16. We identified four smallest regions of overlapping (SROs): one at 16p13.11 was found in seven patients; one at 16p12.2 was found in four patients; two close SROs at 16p11.2 were found in twelve patients; finally, six patients were found with atypical rearrangements. Although phenotypic variability was observed, we identified a male bias for Childhood Apraxia of Speech associated to 16p11.2 microdeletions. We also reported an elevated frequency of second-site genomic alterations, supporting the model of the second hit to explain the clinical variability associated with CNV syndromes. Our goal was to contribute to the building of a chromosome 16 disease-map based on disease susceptibility regions. The role of the CNVs of chromosome 16 was increasingly made clear in the determination of developmental delay. We also found that in some cases a second-site CNV could explain the phenotypic heterogeneity by a simple additive effect or a pejorative synergistic effect.

【 授权许可】

Unknown