Parental origin and mechanism of formation of a 46,X,der(X)(pter-->q21.1::p11.4-->pter)/45,X karyotype in a woman with mild Turner syndrome.

OBJECTIVE: To describe the parental origin and the mechanism of formation of a 46,X,der(X)(pter-->q21.1::p11.4-->pter)[23]/45,X[8] karyotype in a patient with mild Turner syndrome. DESIGN: Case report. SETTING: A university hospital. PATIENT(S): A 23-year-old woman with normal height, gonadal dysgenesis, and mild Turner stigmata. INTERVENTION(S): Genotype-phenotype correlation, array-based copy number analysis, fluorescence in situ hybridization with locus-specific probes, and microsatellite marker-mediated haplotype analysis subsequent to whole genome amplification of microdissected chromosomes. MAIN OUTCOME MEASURES: Genotype-phenotype correlation, mechanism of formation, and parental origin. RESULT(S): Formation in paternal meiosis by refolding in itself and unequal recombination between Xp and Xq were found as the most likely mechanism of formation. CONCLUSION(S): Formation of der(X) chromosomes in females can be more complex than previously thought. The nearly normal height of this patient could be explained by a combination of trisomy of the Xp-located SHOX gene and mosaicism with a 45,X cell line.

Familial 14.5 Mb interstitial deletion 13q21.1-13q21.33: clinical and array-CGH study of a benign phenotype in a three-generation family.

We report on the clinical and cytogenetic findings as well as the array-based characterization of an interstitial familial 13q21 deletion initially recognized by standard karyotyping. Although 13q deletions are known to imply a wide variability of clinical consequences, the deletion carriers of the familial deletion in three generations did not reveal a relevant phenotype. The breakpoints and the deletion size in all three carrier individuals were determined by molecular karyotyping confirming a large 14.5 Mb deletion encompassing the 13q21.1-13q21.33 region identical in all three carriers. Gene paucity and the lack of dosage-sensitive genes in the delineated region might explain the apparently innocuous nature of this chromosomal anomaly. The example of this family presents evidence for describing the chromosomal region 13q21.1-13q21.33 as a large euchromatic variant or benign copy number variation without phenotypic consequences. Our data underline the importance of a phenogenetic approach combining clinical and laboratory evidence in the interpretation of segmental chromosomal anomalies especially in genetic counseling related to prenatal diagnosis.

Complex rearranged small supernumerary marker chromosomes (sSMC), three new cases; evidence for an underestimated entity?

BACKGROUND: Small supernumerary marker chromosomes (sSMC) are present ~2.6 x 106 human worldwide. sSMC are a heterogeneous group of derivative chromosomes concerning their clinical consequences as well as their chromosomal origin and shape. Besides the sSMC present in Emanuel syndrome, i.e. der(22)t(11;22)(q23;q11), only few so-called complex sSMC are reported. RESULTS: Here we report three new cases of unique complex sSMC. One was a de novo case with a dic(13 or 21;22) and two were maternally derived: a der(18)t(8;18) and a der(13 or 21)t(13 or 21;18). Thus, in summary, now 22 cases of unique complex sSMC are available in the literature. However, this special kind of sSMC might be under-diagnosed among sSMC-carriers. CONCLUSION: More comprehensive characterization of sSMC and approaches like reverse fluorescence in situ hybridization (FISH) or array based comparative genomic hybridization (array-CGH) might identify them to be more frequent than only ~0.9% among all sSMC.

New immortalized cell lines of patients with small supernumerary marker chromosome: towards the establishment of a cell bank.

Sixteen newly established cell lines with small supernumerary marker chromosomes (sSMC) derived from chromosomes 1, 2, 4, 6, 7, 8, 14, 15, 16, 18, 19, 21, and 22 are reported. Two sSMC are neocentric and derived from 15q24.1-qter and 2q35-q36, respectively. Two further cases each present with two sSMC of different chromosomal origin. sSMC were characterized by multicolor fluorescence in situ hybridization for their chromosomal origin and genetic content. Moreover, uniparental disomy of the sister chromosomes of the sSMC was excluded in all nine cases studied for that reason. The 16 cases provide information to establish a refined genotype-phenotype correlation of sSMC and are available for future studies.

Impact of prenatal diagnosis on the prevalence of live births with Down syndrome in the eastern half of Switzerland 1980-1996.

OBJECTIVES AND METHODS: To investigate the impact of prenatal diagnosis on trisomy 21 live births, we collected all prenatal and postnatal trisomy 21 cases (n = 1096) in the eastern half of Switzerland for the years 1980-1996. RESULTS: Despite increasing prenatal detection rates of trisomy 21 foetuses (an increase of 169% in the last 5 versus the first 5 years of the study period) and subsequent termination of pregnancies, the number of liveborn Down syndrome children remained constant. The reason is a shift towards a higher mean maternal age from 28 to 30 years between 1980 and 1996. If mean maternal age at delivery was considered, the observed increase of trisomy 21 conceptions matched well with the calculated figures. CONCLUSION: If the tendency to have pregnancies at a more advanced age continues and if the use of prenatal diagnosis does not increase, an increase in incidence of Down syndrome liveborns may be expected in the first decades of the 21st century.