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

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.

Chromosome 4q deletion syndrome: 4q13.3-q21.23 deletion syndrome with mental retardation, congenital heart disease: a case report and literature review

“…In a Lithuanian family [12], the 4q13.3 microdeletion was detected in three affected individuals with the common clinical manifestations of short stature, congenital heart defects, and mild facial abnormalities. ADAMTS3, ANKRD17, and RNU4ATAC9P were screened in key regions of gene defects as candidate genes for intellectual disability, growth retardation, and congenital heart defects.…”

“…Peripheral blood cell examination showed a white blood cell count 14.0×10 9 /L, neutrophil percentage 42.9%(↓), lymphocyte percentage 45.4%(↑),red blood cell 2.34×10 12 /L, hemoglobin concentration 106g/L(↓), and platelet count 591×10 9 /L(↑), C-reactive protein 0.91mg/L. Echocardiography noted a atrial septal defect.…”

CRISPR/Cas9 model of prostate cancer identifies Kmt2c deficiency as a metastatic driver by Odam/Cabs1 gene cluster expression

“…Interestingly, the genes included in this region have not been previously associated with cancer. However, we generated metastatic cell clones from 8g tumors and induced mutations in Odam and Cabs1 66 . Orthotopically grafting the cell clones resulted in reduced tumor size when Odam and Cabs1 were mutated, which was not observed in vitro.…”

Antenatal description of large 4q13.2q21.23 deletion and outcomes

“…Those breakpoints overlap two clusters of described microdeletion syndromes of cytogenetic band 4q13 and 4q21. ADAMTS3, ANKRD17 and NU4ATAC9P through the proximal bound are candidates for intellectual disability, growth retardation and congenital heart defect; PRKG2 and RASGEF1B for intellectual disability and speech defect; HNRNPD and HNRNPDL for growth retardation and hypotonia (Bhoj et al., 2013 ; Hu et al., 2017 ; Komlósi et al., 2015 ; Maldžienė et al., 2020 ).…”