Clinical and molecular cytogenetic description of a female patient with de novo 18q inversion duplication/deletion

Abstract

The genetic causes of global developmental delay (GDD) and intellectual disability (ID) are heterogeneous. Chromosomal imbalance has been recognized as the most frequent cause of ID for years. We describe the report of a female patient aged 1 year and 5 months at presentation who had GDD, prenatal growth retardation, failure to thrive, microcephaly, dysmorphic facial features including: broad forehead, high anterior hair line with sparse scalp hair, wide palpebral fissures, long eye lashes, blue sclera, sparse arched eye brows, prominent and wide nasal root, hypertelorism, micrognathia and dysplastic low set ears in addition to widely spaced nipples, bilateral clenched fists, camptodactyly, rocker bottom feet and brittle nails.. Her karyotype revealed 46,XX,add (18)(q23). Comprehensive cytogenomic analysis was performed using multiplex ligation-dependent probe amplification (MLPA), fluorescence in situ hybridization (FISH), and aCGH techniques to determine the parental origin and the possible mechanism responsible for this abnormal karyotype. Both parents had normal karyotypes. MLPA and FISH analysis for the patient revealed deletion of 18q subtelomere, and whole chromosome paint (WCP) associated with inverted DAPI indicated that all the duplicated segments originated from chromosome 18 and there was inversion of 18q segment. Array CGH identified 55.8-Mb duplicated segment and 614-kb deleted terminal 18q. Single nucleotide polymorphism (SNP) analysis for the patient and the parents revealed that the duplicated and deleted 18q regions originated from paternal chromosome 18. These findings suggested that the event occurred during paternal meiosis or early postzygotic stage. The suggested mechanism responsible for this type of rearrangement is nonhomologous end point recombination and U-type exchange.