Molecular characterization of distal 4q duplication in two patients using oligonucleotide array-based comparative genomic hybridization (oaCGH) analysis

• Published in: American journal of medical genetics. Part A Vol. 164A; no. 4; pp. 1069 - 1074
• Main Authors: Thapa, Monika, Asamoah, Alexander, Gowans, Gordon C., Platky, Kathryn C., Barch, Margaret J., Mouchrani, Patricia, Rajakaruna, Cecilia, Hersh, Joseph H.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01-04-2014; Wiley Subscription Services, Inc
• Subjects: Abnormalities, Multiple - genetics; characterization; Child, Preschool; Chromosomes, Human, Pair 4 - genetics; Comparative Genomic Hybridization - methods; Genes, Duplicate; genomic; Humans; Male; oaCGH; Phenotype; pure duplication; Trisomy - genetics; oaCGH; genomic; pure duplication; 4q; characterization
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.36396

Pure/direct duplications on the long arm of chromosome 4 represent an infrequent chromosomal finding. Description of clinical findings in 30 patients has resulted in defining the 4q‐associated phenotype. However, such duplications have not been molecularly or genomically characterized yet, limiting genotype–phenotype correlation. We report on the first two patients with a duplication involving the distal third of 4q that are characterized molecularly and genomically. Clinical features in our patients typical of 4q duplication syndrome included mild intellectual disability, cranial malformation, minor facial dysmorphism, and digital anomaly. Duplication of the segment 4q33–4q34, appears to be the critical region resulting in the phenotype associated with 4q duplication syndrome. The genes GLRA3, GMP6A that are invovled in neurogenesis and HAND2 in craniofacial development, within the duplicated region of 4q, may play a key role in the clinical phenotype. As more reporting on molecular characterization of 4q duplication becomes available, the role of these underlying genes may become clearer. © 2014 Wiley Periodicals, Inc.