A case report of familial 4q13.3 microdeletion in three individuals with syndromic intellectual disability

• Main Authors: Živilė Maldžienė, Evelina M. Vaitėnienė, Beata Aleksiūnienė, Algirdas Utkus, Eglė Preikšaitienė
• Format: Article
• Language: English
• Published: BMC 2020-04-01
• Series: BMC Medical Genomics
• Subjects: 4q13.3 microdeletion; ADAMTS3; ANKRD17; COX18; Intellectual disability; Congenital anomalies
• Online Access: http://link.springer.com/article/10.1186/s12920-020-0711-4

Abstract Background Interstitial 4q deletions are rare chromosomal alterations. Most of the previously reported deletions involving the 4q13.3 region are large chromosomal alterations with a common loss of band 4q21 resulting in marked growth restriction, severe intellectual disability, and absent or severely delayed speech. A microdeletion of 4q13.3 hasn’t been previously reported. We discuss the involvement of genes and the observed phenotype, comparing it with that of previously reported patients. Case presentation We report on a 4q13.3 microdeletion detected in three affected individuals of a Lithuanian family. The clinical features of two affected children and their affected mother are very similar and include short stature, congenital heart defect, skeletal anomalies, minor facial anomalies, delayed puberty, and intellectual disability. Whole genome SNP microarray analysis of one child revealed an interstitial 4q13.3 microdeletion, 1.56 Mb in size. FISH analysis confirmed the deletion in the proband and identified the same deletion in her affected sib and mother, while it was not detected in a healthy sib. Deletion includes ADAMTS3, ANKRD17, COX18, GC, and NPFFR2 protein-coding genes. Conclusions Our findings suggest that 4q13.3 microdeletion is a cause of a recognizable phenotype of three affected individuals. The detected microdeletion is the smallest interstitial deletion in 4q13. We highlight ADAMTS3, ANKRD17 and RNU4ATAC9P as candidate genes for intellectual disability, growth retardation and congenital heart defect.