12q14 microdeletion associated with HMGA2 gene disruption and growth restriction

• Published in: American journal of medical genetics. Part A Vol. 158A; no. 11; pp. 2925 - 2930
• Main Authors: Alyaqoub, Fadel, Pyatt, Robert E., Bailes, Andrea, Brock, Amanda, Deeg, Carol, McKinney, Aimee, Astbury, Caroline, Reshmi, Shalini, Shane, Kate P., Thrush, Devon Lamb, Sommer, Annemarie, Gastier‐Foster, Julie M.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.11.2012; Wiley-Liss; Wiley Subscription Services, Inc
• Subjects: 12q14 microdeletion; Biological and medical sciences; Child; Chromosome Deletion; Chromosomes, Human, Pair 12; Comparative Genomic Hybridization; Diseases of the osteoarticular system; Dwarfism - diagnosis; Dwarfism - genetics; Female; HMGA2; HMGA2 Protein - genetics; Humans; LEMD3; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical genetics; Medical sciences; osteopoikilosis; short stature; Syndrome; Osteopoikilosis; Microdeletion; Gene; 12q14 microdeletion; Diseases of the osteoarticular system; Genetics; HMGA2; short stature; Disruption; LEMD3; Osteochondrodysplasia; Growth retardation
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.35610

The 12q14 microdeletion syndrome is a rare condition that has previously been characterized by pre‐ and postnatal growth restriction, proportionate short stature, failure to thrive, developmental delay, and osteopoikilosis. Previously reported microdeletions within this region have ranged in size from 1.83 to 10.12 Mb with a proposed 2.61 Mb smallest region of overlap containing the LEMD3, HMGA2, and GRIP1 genes. Here, we report on the identification of a 12q14 microdeletion in a female child presenting with proportionate short stature, failure to thrive, and speech delay. The genomic loss (minimum size 4.17 Mb, maximum size 4.21 Mb) contained 25 RefSeq genes including IRAK3, GRIP1, and the 3′ portion of the HMGA2 gene. This is the first partial deletion of HMGA2 associated with the 12q14 microdeletion syndrome. This case further clarifies the association of LEMD3 deletions with the 12q14 microdeletion syndrome and provides additional support for the role of the HMGA2 gene in human growth. © 2012 Wiley Periodicals, Inc.