Prenatal detection of distal 1q21.1q21.2 microduplication with abnormal ultrasound findings

Abstract

Rationale: 1q21.1 duplication is an uncommon chromosomal submicroscopic imbalance which is associated with growth/mental retardation, dysmorphic features, autism, multiple congenital and neuropsychiatric disorders. Patient concerns: Two pregnant women underwent amniocentesis for cytogenetic analysis and chromosomal microarray analysis (CMA) following abnormal ultrasound findings. Case 1 presented short nasal bone and case 2 showed absent nasal bone, ventricular septal defect and umbilical cord circling in ultrasonic examination. Diagnoses: G-banding analysis showed that the two fetuses presented normal karyotypic results while CMA detected 1.796 Mb (case 1) and 1.242 Mb (case 2) microduplications in the region of 1q21.1q21.2 separately. Furthermore, the CMA also revealed a 1.2 Mb microdeletion of 8p23.3 in case 1. Interventions: The couple in case 1 chose to terminate the pregnancy, while the couple in case 2 continued the pregnancy and finally delivered a male infant who presented low nasal bridge and ventricular septal defect. Outcomes: The 1q21.1q21.2 duplications in our report were located in the distal 1q21.1 region, overlapping with 1q21.1 duplication syndrome. Case 2 was the first reported live birth with 1q21.1 duplication according to prenatal CMA detection in China. Lessons: The genotype-phenotype of 1q21.1 duplication is complicated due to the phenotypic diversity, incomplete penetrance, and lack of obvious characteristics. So it is difficult to predict the postnatal development and health conditions clinically. Hence, long term follow up is necessary for newborn infants with 1q21.1 duplication, irrespective of whether the duplication is de novo or inherited.

Phenotypic and genotypic characterization of 1q21.1 copy number variants: A report of 34 new individuals and literature review

“…It should be noted that ultrasound anomalies occurred in both proximal and distal deletions and duplications (22% of proximal duplications), but were highly variable. No specific pattern was found, and a wide spectrum of anomalies was described including increased nuchal translucency, oligohydramnios, absence of the nasal bone, or duodenal atresia (Ji et al, 2018; Liao et al, 2012; Verhagen et al, 2015; Zhang et al, 2021).…”

“…We also collected all the clinical and genotypic data for individuals with a copy number variant at the 1q21.1 locus from an exhaustive review of the literature using the keyword “1q21.1” in the PubMed database and summarized the phenotype of the patients described in the following cited papers (Alzarka et al, 2018; Basel‐Vanagaite et al, 2011; Benítez‐Burraco et al, 2018; Brunet et al, 2009; Brunetti‐Pierri et al, 2008; Busè et al, 2017; Ceylan et al, 2019; Chen et al, 2018, 2019; Christiansen et al, 2004; Digilio et al, 2013; Dolcetti et al, 2013; Gamba et al, 2016; Gourari et al, 2018; Gulati et al, 2014; Harvard et al, 2011; Ji et al, 2018; Kaymakçalan & Li, 2019; Liao et al, 2012; Mefford et al, 2008; Milone et al, 2016; Pang et al, 2020; Rabinowitz et al, 2018; Rosenfeld et al, 2012; Salinero et al, 2020; Shi et al, 2020; Sun et al, 2015; Taylor & Toko, 2017; Upadhyai et al, 2020; Van Dijck et al, 2015; Veerapandiyan et al, 2019; Velinov & Dolzhanskaya, 2010; Vergult et al, 2013; Verhagen et al, 2015; Wang et al, 2017; Xavier et al, 2018; Zhang et al, 2021). Individuals reported in large cohort studies without detailed phenotype description were not included.…”

Retrospective analysis of genetic etiology and obstetric outcome of fetal cystic hygroma: A single-center study

“…This region is the site of neurocognitive disorders, and patients with this microdeletion exhibit a variety of clinical phenotypes, including developmental delay, heart malformations, autism spectrum disorders, and schizophrenia. [ 24 ] Therefore, the 1q21.1q21.2 microduplication is considered clinically significant and potentially pathogenic. The ultrasound phenotype of the fetus with 1q21.1q21.2 microduplication was isolated CH.…”

Genetic etiology and obstetric outcome analysis of fetal cystic hygroma in a single-center study

“…In another fetus, deletion of 1q21.1q21.2 was identi ed, which is approximately 1.8 Mb in size and contains 23 OMIM genes. This region is the site of neurocognitive disorders, and patients with this microdeletion exhibit a variety of clinical phenotypes, including developmental delay, heart malformations, autism spectrum disorders, and schizophrenia [24]. Therefore, the clinical signi cance of 1q21.1q21.2 microduplication is considered to have clinical signi cance and potentially induce disease.…”