Molecular cytogenetic analysis and clinical manifestations of a case with de novo mosaic ring chromosome 7

Abstract

Aim: Clinical and molecular cytogenetic investigations of a newborn girl exhibiting facial dysmorphism with developmental delay.

Methods: Phenotypic evaluation was first applied to examine the proband's developmental status. Computed tomography and colour transcranial Doppler were used then to investigate her brain structure and function. Subsequently, chromosomal abnormalities were examined by karyotyping and fluorescent in situ hybridization was performed to investigate size of fragments lost at the two distal ends of the ring chromosome 7. In addition, multicolour banding was applied to rule out structural rearrangement occurs in between the ring chromosome 7.

Results: The proband was born with mosaic supernumerary ring chromosome 7, without a normal karyotype detected in the peripheral blood lymphocytes. The distal arm of chromosome 7p (at least 255 kb from the telomere) was part of an extra ring chromosome 7. In addition, the distal arm of 7q, at least 8 kb from the telomere, was missing. There was no other chromosomal rearrangement detected by multicolour banding.

Interpretation: This is the 19th reported case of complete ring chromosome 7 mosaicism and the first survived case with mosaic supernumerary ring 7 without a normal karyotype detected in the peripheral lymphocytes.

Figure 1

Pictures taken from the front (A) and from the side (B) of the proband at her age of one year and 10 months old. Facial dysmorphism including hypotelorism, midface hypoplasia and high arch palate were noted. Choanal stenosis was suspected because of noise nasal breathing since birth.

Figure 2

Mosaic karyotypes of the proband: Out of 100 analyzed cells, 46, XX,r(7) (p22q36) (A) was detected in 75 cells (75%); 45,XX, -7 (B) in 12 cells (12%); 47,XX,r(7)(p22q36),+ r(7)(p22q36) (C) in five cells (5%); and 46, XX, dic r (7;7)(p22q36;p22q36)(D) in four cells (4%).

Figure 3

Flourescent In Situ Hybridization (FISH) using 7p and 7q sub-telomere probes: FISH with 7pter probe indicates subtelomeric region at least 255 kb from telomere remained intact in all rings (A, B and C). However, the 7qter probe indicates that at least 8 kb from telomere was missing in the ring (D).

Figure 4

Multicolor banding of normal and ring chromosome 7: Multicolor banding probes that specifically detect various regions along chromosome 7 were hybridized to metaphases; no rearrangement was observed in normal ring 7 chromosomes.