Inherited unbalanced translocation (4p16.3p15.32 duplication/8p23.3p23.2deletion) in the four generation pedigree with intellectual disability/developmental delay

Abstract

Chromosomal copy number variants (CNVs) are an important cause of congenital malformations and mental retardation. This study reported a large Chinese pedigree (4-generation, 76 members) with mental retardation caused by chromosome microduplication/microdeletion. There were 10 affected individuals with intellectual disability (ID), developmental delay (DD), and language delay phenotypes. SNP array analysis was performed in the proband and eight patients and found all of them had a microduplication of chromosome 4p16.3p15.2 and a microdeletion of chromosome 8p23.3p23.2. The high-resolution karyotyping analysis of the proband had unbalanced karyotype [46, XY, der(8)t(4;8)(p15.2;p23.1)mat], his mother had balanced karyotype [46, XX, t(4;8) (p15.2;p23.1)], whereas his father had normal karyotype [46,XY]. Fluorescence in situ hybridization (FISH) analysis further confirmed that the proband’s mother had a balanced translocation between the short arm terminal segment of chromosome 4 and the short arm end segment of chromosome 8, ish t(4;8)(8p + ,4q + ;4p + ,8q +). In conclusion, all the patients inherited chromosomes 8 with 4p16.3p15.2 duplication and 8p23.3p23.2 deletion from their parental balanced translocation, which might be the cause of the prevalence of intellectual disability. Meanwhile, 8p23.3p23.2 deletion, rather than 4p16.3p15.2 duplication might cause a more severe clinical syndrome.

Karyotype and molecular cytogenetic analysis among sample of Iraqi children with idiopathic intellectual disability

“…Chromosomal abnormalities, including duplications, deletions, and Fragile X syndrome, were prevalent, underlining the significance of genomic examinations in diagnosing growth, developmental, and congenital anomalies [21,22] . The study highlighted the association of dysmorphic features, epilepsy, family history, and ID level with positive parental consanguinity, though a significant association was not established, likely due to the small sample size [23,24] . The research found that duplications were mostly associated with mild ID and consanguinity, similar to findings of deletions and brain atrophy [25] .…”

Clinical comparison between terminal and interstitial 4q deletion in two unrelated children

“…Anomalies have been reported affecting the brain (ventriculomegaly, cortical atrophy and prominent ventricles, large occipital encephalocele) [12][13][14], eyes (bilateral hypermetropia, pigmentary retinal degeneration, microphthalmia) [15][16][17][18], cleft palate and Pierre Robin syndrome [3,5,7,[19][20][21], heart (enlarged right atrium and ventricle, small atrial septal defect, abnormal structure and function of both ventricles and double inferior vena cava, coarctation of the aorta and interventricular communication, both valvar pulmonic stenosis, cor triatriatum) [3,8,[22][23][24], kidneys (duplicated left intrarenal collecting system, polycystic kidney, bilateral extrarenal pelvis dysplastic cystic kidneys) [3, 9, 24-26], genital defects [27], limb development disorder (irregularity of the outline of the distal phalanx of the 4th digit, rudimentary left thumb with absence of right thumb, bilateral absence of ulna) [28][29][30][31]. Craniofacial dysmorphism has frequently been reported with signs that are not speci cally diagnostic [32][33][34][35][36], as well cognitive involvement [17,[37][38][39][40][41], de cit of growth [25,34] and epileptic seizures [22,25]. Other reported anomalies include congenital hearing impairment [18, 42], hypercalciuria and kidney calci cation [43], familial combined hyperlipidemia <...…”