Clinical Characterization and Cytogenetic-Molecular Study of a Patient with a Ring Chromosome 12

Abstract

Introduction: Ring chromosomes generally result from the fusion of breaks at the ends of both arms of a chromosome, typically leading to the loss of genetic material from these ends.

Case presentation: We report the case of a four-year-old patient who exhibits multiple café-au-lait spots, hypochromic spots, bitemporal narrowing, bilateral epicanthus, patent foramen ovale, and multiple brain abnormalities identified through magnetic resonance imaging. Karyotyping revealed a ring chromosome: r(12). Chromosomal microarray analysis revealed a ∼3.6 Mb deletion in the short arm and a ∼1.2 Mb deletion in the long arm of chromosome 12. The patient's phenotype is consistent with these genetic imbalances. To investigate ring chromosome instability and mosaicism, 200 metaphases were analyzed using G-banding and FISH with a whole chromosome painting probe, identifying 166 cells with a 46,XX,r(12) karyotype, 20 cells with monosomy 12, eight with a dicentric ring chromosome, three with two monocentric rings, two with two interlocked dicentrics, and one with an open ring chromosome.

Conclusion: This study provided a detailed characterization of the ring rearrangement of chromosome 12, the first with SNP array, enhancing the understanding of its genetic and phenotypic implications and contributing to expanding knowledge about this condition. Additionally, the findings can aid in better understanding the patient's prognosis, clinical follow-up, and genetic counseling.

Keywords: Café-au-lait spots; Chromosome 12; Formation mechanism; Instability; Ring chromosome.

Fig. 1.

Patient at 4 years and 20 days old. a One long hypochromic spot on the right lower limb. b–d Multiple café-au-lait spots and small hypochromic spots on the abdomen and hands.

Fig. 2.

Partial karyotype of the patient with r(12). Under G-banding, in addition to the normal chromosome 12, there is a monocentric ring chromosome 12 (a), two individual monocentric ring chromosomes (b), a dicentric ring chromosome 12 (c), two interlocked dicentric ring chromosomes (d), loss of ring chromosome 12 (e), and, under FISH, a cell in metaphase with a normal chromosome 12 and two interlocked dicentric ring chromosomes (f) and the same metaphase in gray scale (g) and metaphase with loss of ring chromosome 12 (h).