Prenatal Diagnosis of a Female Fetus with Ring Chromosome 9, 46,XX,r(9)(p24q34), and a de novo Interstitial 9p Deletion

Abstract

Ring chromosomes are circular structures formed as a result of breaks in the chromosome arms and the fusion of the proximal broken ends with a loss of distal material, or by fusion of dysfunctional telomeres without any loss. The mechanism underlying this process has not yet been sufficiently explained. Commonly, rings occur as acquired genetic abnormalities; however, sometimes they are found as constitutional aberrations with a prevalence of around 1:50,000 live births. Here, we present a new case of r(9) in a female fetus with intrauterine growth retardation and slight craniofacial dysmorphisms. Both parents had a normal phenotype. Amniotic fluid karyotype showed r(9)(p24q34). An array CGH revealed 3 deletion segments: a ring chromosome with a 2.57-Mb deletion at 9pterp24.2 (chr9:163,131-2,729,722), a 2.60-Mb deletion at 9q34.3qter (chr9:138,523,302-141,122,055), and also a 0.15-Mb interstitial deletion at 9p24.1 (chr9:5,090,443-5,235,765). These deletions overlap with proposed regions for the 9p24.3 deletion and Kleefstra syndrome. Segregation analysis revealed a maternal origin of the rearranged chromosome. We conclude that both the ring chromosome and the interstitial deletion occurred de novo. This last deletion has not been reported before. Prenatal array CGH, combined with fine mapping of breakpoints contributes to the assessment of genotype-phenotype correlations.

Ring chromosome formation by intra‐strand repairing of subtelomeric double stand breaks and clinico‐cytogenomic correlations for ring chromosome 9

“…The infectious complications, which candidate genes could be CD274 and IL33 at 9p24.1, were seen in the r(9) patient of Qin et al (2016). The four patients with deletion of 9q involving the EHMT1 gene showed features of 9q34.3 deletion syndrome (La Cour Sibbesen et al, 2013; Penacho et al, 2014; Lyu et al, 2019, and present patient). Other phenotypic variations could be caused by triple‐sensitivity genes from an extra duplication in the r(9) of Marsudi et al (2018) and the present patient.…”

“…Review of literature found seven patients of r(9) with clinical and cytogenomic findings, including one prenatal fetus (Penacho et al, 2014) and six postnatal patients (La Cour Sibbesen, Jespersgaard, Alosi, Bisgaard, & Tümer, 2013; Laursen et al, 2015; Sivasankaran, Kanakavalli, Anuradha, Samuel, & Kandukuri, 2016; Qin et al, 2016; Marsudi et al, 2018; Lyu, Li, Li, Shang, & Ma, 2019). Ring chromosome instability index (RCII) was defined as the percentage of cells with ring chromosome variants and loss of ring chromosome.…”