Supernumerary marker chromosomes in man: parental origin, mosaicism and maternal age revisited

Abstract

The details of all cytogenetic abnormalities diagnosed in the Wessex Regional Genetics Laboratory (WRGL) since 1967 to the present day have been recorded in the Salisbury Treasury of Interesting Chromosomes (STOIC). From this resource, we identified 137 patients with constitutional autosomal supernumerary marker chromosomes (SMC) ascertained in four principal groups: (i) 37% with abnormal phenotypes; (ii) 7% couples with reproductive difficulties; (iii) 47% antenatal diagnoses and (iv) 9% miscellaneous. Overall, 81 (59%) SMCs were mosaics and 56 (41%) nonmosaics. Of the 109 cases with known parental origins, 70% were de novo, 19% maternally and 11% paternally inherited. The chromosomal origins of 112/137 (82%) of the SMCs have been determined by fluorescence in situ hybridization (FISH). In all, 36/112 (32%) were derived from nonacrocentric autosomes, and 76/112 (68%) from the acrocentric autosomes 13/21, 14, 15 and 22. Of these acrocentric SMCs, 39 (51%) were derived from chromosome 15, so that SMC(15) constituted 39/112 (35%) of all SMCs with known chromosomal origins. The frequencies with which mosaicism was observed varied considerably according to the chromosomal origin of the SMCs and accounted for 8/39 (20%) SMC(15), 13/37 (35%) SMCs from other acrocentrics and 25/36 (69%) of nonacrocentric SMCs. The data were analysed for parental age effects, and only de novo SMC(15)s were found to be associated with a significantly increased maternal age.

Rare chromosome abnormalities, prevalence and prenatal diagnosis rates from population-based congenital anomaly registers in Europe

“…Our predominance of markers derived from chromosome 15, in the few that were further analysed, is entirely in keeping with other reports. 9,22,23 There are no comparable studies on the prevalence of non-21, 13 or 18 mosaic and non-mosaic trisomies, but Forabosco et al 24 found a rate of 0.22/10 000 births. Our rate of 0.86 included the 22% of cases not reported to be detected prenatally.…”

“…7,8 Marker chromosomes are known to vary widely phenotypically, with apparently normal babies at birth remaining unkaryotyped. [9][10][11] Thus, the prevalence from cytogenetic surveys does not tell us the diagnosed prevalence among babies. On the other hand, the advent of prenatal screening has led to earlier detection of some babies with chromosome abnormalities who would not survive to live births, and to the increased detection of chromosomal abnormalities, which result in phenotypically normal children.…”

Forty-two supernumerary marker chromosomes (SMCs) in 43 273 prenatal samples: chromosomal distribution, clinical findings, and UPD studies

“…The mother reported a normal development at the age of 6 months. (8). The hybridization signal with the alphoid probe for 8 fully covered the SMC, suggesting the absence of euchromatin.…”

“…All had occurred de novo. There were eight cases (61.5%) of heterochromatic (class III) SMCs and of these, five resulted in children without anomalies carrying SMCs 6,8,11,17 …”

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

“…However, there are exceptions to this, such as when there are imprinting effects from uniparental disomy, or low level, tissue specific mosaicism for the sSMC in a parent without phenotypic manifestations (Graf et al, 2006). sSMCs are also classified as satellited or non-satellited and mosaic or non-mosaic (Crolla et al, 2005). It has previously been reported that carrying an accessory bisatellited sSMC was not a risk factor for having abnormal offspring, spontaneous abortion or nondisjunction (Kumar et al, 1997).…”