Short stature, digit anomalies and dysmorphic facial features are associated with the duplication of miR-17 ~ 92 cluster

Molecular Cytogenetics

Fatih Z Boyar³  Bryant Nguyen³  Maryam Talai³  Arturo Anguiano³  Charles M Strom³  Loretta W Mahon¹  Melissa J Rumple²  Morteza Hemmat³ 

[1] Quest Diagnostics, 8401 Fallbrook Avenue, West Hills, Los Angeles, California 91304, USA;Banner Child Neurology, 5310 W Thunderbird Rd, Ste 301, Glendale, Arizona 85306, USA;Cytogenetics Department, Quest Diagnostics, 33608 Ortega Hwy, San Juan Capistrano, California 92675, USA

关键词: Skeletal defects;    Digital anomaly;    GCP5;    miR-17 ~ 92;    MIR17HG;    miRNA;   

Others  :  1150116
DOI  :  10.1186/1755-8166-7-27

 received in 2014-02-13, accepted in 2014-04-04,  发布年份 2014

【 摘 要 】

MicroRNAs (miRNAs) are key regulators of gene expression, playing important roles in development, homeostasis, and disease. Recent experimental evidence indicates that mutation or deregulation of the MIR17HG gene (miR-17 ~ 92 cluster) contributes to the pathogenesis of a variety of human diseases, including cancer and congenital developmental defects. We report on a 9-year-old boy who presented with developmental delay, autism spectrum disorder, short stature, mild macrocephaly, lower facial weakness, hypertelorism, downward slanting palpebral fissures, brachydactyly, and clinodactyly. SNP-microarray analysis revealed 516 kb microduplication at 13q31.3 involving the entire MIR17HG gene encoding the miR-17 ~ 92 polycistronic miRNA cluster, and the first five exons of the GPC5 gene. Family study confirmed that the microduplication was maternally inherited by the proband and one of his five half-brothers; digit and other skeletal anomalies were exclusive to the family members harboring the microduplication.

This case represents the smallest reported microduplication to date at 13q31.3 and provides evidence supporting the important role of miR-17 ~ 92 gene dosage in normal growth and skeletal development. We postulate that any dosage abnormality of MIR17HG, either deletion or duplication, is sufficient to interrupt skeletal developmental pathway, with variable outcome from growth retardation to overgrowth.

【 授权许可】

   
2014 Hemmat et al.; licensee BioMed Central Ltd.

【 图 表 】

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