Supernumerary marker chromosomes derived from chromosome 6: Cytogenetic, molecular cytogenetic, and array CGH characterization

Abstract

Supernumerary marker chromosomes (SMC) are relatively common in prenatal diagnosis. As the clinical outcomes vary greatly, a better understanding of the karyotype-phenotype correlation for different SMCs will be important for genetic counseling. We present two cases of prenatally detected de novo, small SMCs. The markers were present in 80% of amniocyte colonies in Case 1 and 38% of the colonies in Case 2. The SMCs were determined to be derived from chromosome 6 during postnatal confirmation studies. Although the sizes and the chromosomal origin of the SMCs in these two cases appeared to be similar, the clinical outcomes varied. The clinical manifestations observed in Case 1 included small for gestational age, feeding difficulty at birth, hydronephrosis, deviated septum and dysmorphic features, while the phenotype is apparently normal in Case 2. Array comparative genomic hybridization (CGH) was performed and showed increase in dosage for approximately 26 Mb of genetic material from the proximal short and long arms of chromosome 6 in Case 1. Results of array CGH were uninformative in Case 2, either due to mosaicism or lack of detectable euchromatin. The difference in the clinical presentation in these two patients may have resulted from the difference in the actual gene contents of the marker chromosomes and/or the differential distribution of the mosaicism.

Molecular characterization of 39 de novosSMC: contribution to prognosis and genetic counselling, a prospective study

“…Array-CGH and SNP array are powerful tools for delineating chromosomal imbalances. However, there have been no large series reporting the application of this technology to sSMC in a postnatal (14)(15)(16)(17)(18)(19)(20)(21)(22) or prenatal context (23)(24)(25)(26)(27)(28)(29), or both (30,31). Genotype-phenotype correlations should be extended, and SNP array also offers the possibility to detect uniparental disomy (UPD), in particular, for sSMC derived from chromosome 6, 7, 11 and 20 (32,33).…”

Clinical and genetic characterization of basal cell carcinoma and breast cancer in a single patient

“…Small supernumerary marker chromosomes and also ring chromosomes have been found in several instances as derived from chromosome 6 (Huang et al 2012; Guilherme et al 2012). Deletions at the end of both arms of one allele 6 are often involved in this rare de novo event.…”

Aneurysmal bone cysts and pathologic fracture associated with supernumerary ring chromosome 6 in two unrelated patients

“…A patient with sSMC encompassing 6p21.2‐q11.2 presented with IUGR, severe developmental delay, facial dysmorphism, scoliosis, lax joints, and transient neonatal diabetes (Crolla, Howard, Mitchell, Long, & Dennis, ). An additional patient with a 6p21.2‐q11.2 sSMC was described with IUGR, facial dysmorphism, developmental delay, and epilepsy (Huang et al, ). The remaining patients of characterized sSMC6 consist of small duplicated regions encompassing 6p11.1‐q12.…”

“…The remaining patients of characterized sSMC6 consist of small duplicated regions encompassing 6p11.1‐q12. Phenotypic severity consists of psychomotor delay, hypotonia, congenital heart defects, and facial dysmorphism to phenotypically normal (Huang et al, ; Leite et al, ; Liehr et al, ; Oldak et al, ; Stankiewicz et al, ). Intriguingly, this bone phenotype has been described once before.…”

“…Intrauterine growth retardation (IUGR), mild to severe developmental delay, transient neonatal diabetes mellitus, congenital heart defects, hypotonia, hypogenitalism, hydronephrosis, and vesico‐ureteral junction obstruction are clinical features observed in this disorder. Dysmorphic features can include epicanthic folds, thick upper lips, broad nasal bridge and tip, hypertelorism, and prominent cheeks (Huang, Pearle, Rauen, & Cotter, ; Liehr et al, ; Oldak et al, ).…”