In utero hematopoietic stem cell transplantation in canines: exploring the gestational age window of opportunity to maximize engraftment.

Objective: In utero hematopoietic stem cell transplantation (IUHSCT) is a promising therapy for a variety of congenital disorders. Our objective was to determine the optimal time in gestation for IUHSCT in a canine model.

Methods: IUHSCT was performed in day 31-50 (term 63) fetal canines with CD34+ cells isolated from paternal bone marrow at doses of 0.

X-linked adrenoleukodystrophy: ABCD1 de novo mutations and mosaicism.

X-linked adrenoleukodystrophy (X-ALD) is a progressive peroxisomal disorder affecting adrenal glands, testes and myelin stability that is caused by mutations in the ABCD1 (NM_000033) gene. Males with X-ALD may be diagnosed by the demonstration of elevated very long chain fatty acid (VLCFA) levels in plasma. In contrast, only 80% of female carriers have elevated plasma VLCFA; therefore targeted mutation analysis is the most effective means for carrier detection.

Prenatal detection of a subtle unbalanced chromosome rearrangement by karyotyping, FISH and array comparative genomic hybridization.

Objectives: To explore the advantages and limitations of comparative genomic hybridization to BAC arrays (array CGH) for prenatal diagnosis of a fetus with anomalies and a chromosome abnormality.

Methods: We used karyotype analysis, FISH and array CGH to investigate an unbalanced chromosome rearrangement.

Results: We report a case of a fetus with ultrasound anomalies at 11 weeks' gestation and an unbalanced chromosome translocation [46,XX,der(13)t(2;13)(p25.

Clinical consequences of an increasing trend of preferential use of cultured villi for molecular diagnosis by CVS.

Objective: To compare the use of uncultured versus cultured villus cells for DNA-based prenatal diagnosis.

Methods: A retrospective review of molecular testing of chorionic villus sampling (CVS) cases from 1988-2007. Method of analysis, gestational age (GA) at CVS and at diagnosis, time from procedure to results, results of maternal contamination studies, and the laboratory employed were abstracted from patient charts.

Prenatal diagnosis of mosaic trisomy 8q studied by ultrasound, cytogenetics, and array-CGH.

Mosaic trisomy 8, also known as Warkany syndrome, has a well-characterized constellation of phenotypic findings. Partial trisomy 8, including mosaic cases, has also been reported, with outcome and counseling dependent on the chromosomal segment involved and whether accompanied by partial aneuploidy for other chromosomes. We present a case of a fetus mosaic for trisomy of the entire long arm (q) of chromosome 8 without additional chromosomal aberrations.

X inactivation in triploidy and trisomy: the search for autosomal transfactors that choose the active X.

Only one X chromosome functions in diploid human cells irrespective of the sex of the individual and the number of X chromosomes. Yet, as we show, more than one X is active in the majority of human triploid cells. Therefore, we suggest that (i) the active X is chosen by repression of its XIST locus, (ii) the repressor is encoded by an autosome and is dosage sensitive, and (iii) the extra dose of this key repressor enables the expression of more than one X in triploid cells.

Microphthalmia with linear skin defects (MLS) syndrome evaluated by prenatal karyotyping, FISH and array comparative genomic hybridization.

Objective: To explore the utility of comparative genomic hybridization to BAC arrays (array CGH) for prenatal diagnosis of microphthalmia and linear skin defects syndrome.

Methods: We used karyotype analysis, FISH and array CGH to investigate an X;Y translocation. Replication studies were done on cultured amniocytes and lymphoblasts.

Use of T-cell antibodies for donor dosaging in a canine model of in utero hematopoietic stem cell transplantation.

Aim: Microchimerism following canine in utero hematopoietic stem cell transplantation (IUHSCT) development of T-cell dosing regimens.

Objective: To investigate the use of anti-T-cell antibodies for cell dosing of the donor graft in a canine model of IUHSCT.

Study Design: Canine IUHSCT was performed by ultrasound-guided intraperitoneal injection in days 35-38 of fetal canines with CD34(+) cells at doses of 4.

Frequency of chromosomal abnormalities in spontaneous abortions derived from intracytoplasmic sperm injection compared with those from in vitro fertilization.

No statistical difference was found for the total aneuploidy rate in the spontaneous abortions between intracytoplasmic sperm injection and IVF groups; however, differences in the distribution of chromosomal abnormalities between the two groups were seen.

Autopsy findings of a 37-year-old man with a complex mosaic karyotype involving del(18p), monosomy 13, and trisomy 20.

We report on the autopsy findings of a 37-year-old man with a complex karyotype (mos46,XY,del(18)(p11.1)[14]/46,XY, -13, del (18)(p11.1), +20[8]/47,XY,del(18)(p11.

A reciprocal translocation 46,XY,t(8;9)(p11.2;q13) in a bladder exstrophy patient disrupts CNTNAP3 and presents evidence of a pericentromeric duplication on chromosome 9.

A patient with sporadic bladder exstrophy and de novo apparently balanced chromosomal translocation 46,XY,t(8;9)(p11.2;q13) was analyzed by fluorescence in situ hybridization (FISH) and molecular methods. We were able to map both translocation breakpoints to single genomic clones.

Prenatal detection of an interstitial deletion in 4p15 in a fetus with an increased nuchal skin fold measurement.

Objectives: The detection of an increased nuchal translucency (NT) or nuchal fold (NF) measurement is associated with an increased risk of common aneuploidies. Only rarely is it associated with other types of chromosome abnormalities. We report the prenatal finding of an increased NF in a fetus with an interstitial 4p deletion.

Reevaluating confined placental mosaicism.

Chromosomal mosaicism was found in 38 of 4,000 chorionic villus samples examined from 1998 to 2003. A small fraction of these (5/38) were confirmed as true mosaics by analysis of amniotic fluid. Twenty-nine cases that fit the definition of confined placental mosaicism were followed with clinical and cytogenetic analysis throughout the pregnancy, at birth and in a few cases into infancy.

Transcript level alterations reflect gene dosage effects across multiple tissues in a mouse model of down syndrome.

Human trisomy 21, which results in Down syndrome (DS), is one of the most complicated congenital genetic anomalies compatible with life, yet little is known about the molecular basis of DS. It is generally accepted that chromosome 21 (Chr21) transcripts are overexpressed by about 50% in cells with an extra copy of this chromosome. However, this assumption is difficult to test in humans due to limited access to tissues, and direct support for this idea is available for only a few Chr21 genes or in a limited number of tissues.

In utero hematopoietic stem cell transplantation with haploidentical donor adult bone marrow in a canine model.

Objective: Chimerism can be achieved in a canine model of in utero bone marrow transplantation with > or =1 x 10(8) CD34(+) haploidentical donor cells per kilogram without graft-versus-host disease.

Study Design: In utero bone marrow transplantation was performed by ultrasound-guided intraperitoneal infusion in 30- to 41-day-old canines with CD34(+) selected cells from paternal bone marrow at doses of 1.3 x 10(8) to 2.