Cytogenetic and molecular evaluation of 241 small supernumerary marker chromosomes: Cooperative study of 19 Italian laboratories

Abstract

Purpose: We evaluated the experiences of 19 Italian laboratories concerning 241 small supernumerary marker chromosomes (sSMCs) with the aim of answering questions arising from their origin from any chromosome, their variable size and genetic content, and their impact on the carrier's phenotype. Methods: Conventional protocols were used to set up the cultures and chromosome preparations. Both commercial and homemade probes were used for the fluorescent in situ hybridization analyses. Results: A total of 113 of the 241 sSMCs were detected antenatally, and 128 were detected postnatally. There were 52 inherited and 172 de novo cases. Abnormal phenotype was present in 137 cases (57%), 38 of which were antenatally diagnosed. A mosaic condition was observed in 87 cases (36%). In terms of morphology, monocentric and dicentric bisatellited marker chromosomes were the most common, followed by monocentric rings and short-arm isochromosomes. The chromosomes generating the sSMCs were acrocentric in 132 cases (69%) and non-acrocentric chromosomes in 60 cases (31%); a neocentromere was hypothesized in three cases involving chromosomes 6, 8, and 15. The widespread use of molecular cytogenetic techniques in diagnostic laboratories has improved diagnostic quality, especially in prenatal cases. However, one of the few major problems remaining is the identification of the nature and origin of small supernumerary marker chromosomes (sSMCs).sSMCs display a wide range of morphology and occur at highly variable incidence, 1,2 thus giving rise to considerable problems in genetic counseling, particularly during prenatal testing. Only the combined use of conventional and molecular

Familial small supernumerary marker chromosomes are predominantly inherited via the maternal line

“…For those cases (Table 1), we find 72 sSMC inherited from the mother versus 30 sSMC inherited from the father, which is similar to the 2.4:1 ratio suggested in the paper by Dalprà et al 1 for the parental origin of sSMC. As detailed in Table 1, this ratio is more expressed in sSMC derived from non-acrocentric chromosomes.…”

“…As detailed in Table 1, this ratio is more expressed in sSMC derived from non-acrocentric chromosomes. The data presented here is independent of that of Dalprà et al, 1 as there were no details available on their individual patients.…”

Thirty-two new cases with small supernumerary marker chromosomes detected in connection with fertility problems: Detailed molecular cytogenetic characterization and review of the literature

“…This rate is similar for the overall population [~70% according to (3)]. Also it was not unexpected that sSMC [15] was the most frequently observed (4,8). However, the sSMC [14] rate in the infertile patients from the present study was, at 15%, ~4 times higher than in all sSMC cases studied for their chromosomal origin (3,4,8) (Fig.…”

“…Several mechanisms seem to be involved here. (i) It has been shown repeatedly (12,15) that sSMC are more likely to be carried forward through the maternal line, thus, selection for gametes without an additional extra chromosome during oogensis can be postulated [for more details see also (12); for centromeric drive see (16)]. (ii) It has also been suggested that any kind of chromosomal aberration can reduce the ability of correct chromosomal pairing during meiosis I (1), which can cause fertility problems especially in males (17).…”

Case Report A small supernumerary marker chromosome, derived from chromosome 22, possibly associated with repeated spontaneous abortions

“…In our case, the sSMC was also derived from chromosome 22 and a normal phenotype was observed. Although some studies provided indications concerning the pathologic phenotype and the risk accordingly associated with an sSMC (Warburton, 1991;Crolla, 1998), the published data still do not allow any definite conclusions to be drawn concerning karyotype-phenotype correlations (Dalprà et al, 2005).…”