Ioannis Papoulidis

Dual testing with QF-PCR and karyotype analysis for prenatal diagnosis of chromosomal abnormalities. Evaluation of 13,500 cases with consideration of using QF-PCR as a stand-alone test according to referral indications.

Evaluate the results obtained from Quantitative Fluorescent (QF)‐PCR and conventional karyotype analysis to determine the advantages and disadvantages of dual testing in prenatal diagnosis.

Turner's syndrome and pregnancy: has the 45,X/47,XXX mosaicism a different prognosis? Own clinical experience and literature review

Turners syndrome is characterized by an ovarian failure which occurs in most cases before puberty and leads to infertility. In less than 10% of women with Turner syndrome, puberty may occur and spontaneous pregnancies is possible but with a high risk of fetal loss, chromosomal and congenital abnormalities. We present the case of a 33-year-old woman with a mosaic Turners syndrome karyotype 45,X/47,XXX who conceived spontaneously and had two successful pregnancies. Short stature was the only manifestation of Turners syndrome. In the present report, we reviewed the available literature on the fertility of women with Turners syndrome and the phenotypic effects of mosaicism for a 47,XXX cell line in Turners syndrome.

Routine use of array comparative genomic hybridization (aCGH) as standard approach for prenatal diagnosis of chromosomal abnormalities. Clinical experience of 1763 prenatal cases.

This study aims to evaluate the diagnostic yield of comparative genomic hybridization microarrays (aCGH) and compare it with conventional karyotype analysis of standard >5‐Mb resolution.

A patient with partial trisomy 21 and 7q deletion expresses mild Down syndrome phenotype

BACKGROUND Down syndrome (DS) is the most common aneuploidy in live-born individuals and it is well recognized with various phenotypic expressions. Although an extra chromosome 21 is the genetic cause for DS, specific phenotypic features may result from the duplication of smaller regions of the chromosome and more studies need to define genotypic and phenotypic correlations. CASE REPORT We report on a 26 year old male with partial trisomy 21 presenting mild clinical symptoms relative to DS including borderline intellectual disability. In particular, the face and the presence of hypotonia and keratoconus were suggestive for the DS although the condition remained unnoticed until his adult age array comparative genomic hybridization (aCGH) revealed a 10.1 Mb duplication in 21q22.13q22.3 and a small deletion of 2.2 Mb on chromosomal band 7q36 arising from a paternal translocation t(7;21). The 21q duplication encompasses the gene DYRK1. CONCLUSION Our data support the evidence of specific regions on distal 21q whose duplication results in phenotypes recalling the typical DS face. Although the duplication region contains DYRK1, which has previously been implicated in the causation of DS, our patient has a borderline IQ confirming that their duplication is not sufficient to cause the full DS phenotype.

Prenatal diagnosis of Wolf-Hirschhorn syndrome confirmed by comparative genomic hybridization array: report of two cases and review of the literature

Wolf-Hirschhorn syndrome (WHS) is a well known genetic condition caused by a partial deletion of the short arm of chromosome 4. The great variability in the extent of the 4p deletion and the possible contribution of additional genetic rearrangements lead to a wide spectrum of clinical manifestations. The majority of the reports of prenatally diagnosed WHS cases are associated with large 4p deletions identified by conventional chromosome analysis; however, the widespread clinical use of novel molecular techniques such as array comparative genomic hybridization (a-CGH) has increased the detection rate of submicroscopic chromosomal aberrations associated with WHS phenotype. We provide a report of two fetuses with WHS presenting with intrauterine growth restriction as an isolated finding or combined with oligohydramnios and abnormal Doppler waveform in umbilical artery and uterine arteries. Standard karyotyping demonstrated a deletion on chromosome 4 in both cases [del(4)(p15.33) and del(4)(p15.31), respectively] and further application of a-CGH confirmed the diagnosis and offered a precise characterization of the genetic defect. A detailed review of the currently available literature on the prenatal diagnostic approach of WHS in terms of fetal sonographic assessment and molecular cytogenetic investigation is also provided.

Tetrasomy 9p Mosaicism Associated with a Normal Phenotype in Two Cases

Tetrasomy 9p is a rare chromosomal syndrome and about 30% of known cases exhibit mosaicism. Approximately 50 of the reported cases with tetrasomy 9p mosaicism show a characteristic facial appearance, growth failure, and developmental delay. However, 3 patients with mosaicism for isochromosome 9p and a normal phenotype have also been reported. We report 2 additional cases of clinically normal young females with tetrasomy 9p mosaicism, one of whom also exhibited X chromosome aneuploidy mosaicism leading to an overall of 6 different cell lines. STR analysis performed on this complex mosaic case indicated that the extra isochromosome was of maternal origin while the X chromosome aneuploidy was of paternal origin, indicating a postzygotic event.

Detailed molecular and clinical investigation of a child with a partial deletion of chromosome 11 (Jacobsen syndrome)

BackgroundJacobsen syndrome (JBS) is a rare chromosomal disorder leading to multiple physical and mental impairment. This syndrome is caused by a partial deletion of chromosome 11, especially subband 11q24.1 has been proven to be involved. Clinical cases may easily escape diagnosis, however pancytopenia or thrombocytopenia may be indicative for JBS.ResultsWe report a 7.5 years old boy presenting with speech development delay, hearing impairment and abnormal platelet function. High resolution SNP oligonucleotide microarray analysis revealed a terminal deletion of 11.4 Mb in size, in the area 11q24.1-11qter. This specific deletion encompasses around 170 genes. Other molecular techniques such as fluorescence in situ hybridization and multiplex ligation-dependent probe amplification were used to confirm the array-result.DiscussionOur results suggest that the identification and detailed analysis of similar patients with abnormal platelet function and otherwise mild clinical features will contribute to identification of more patients with 11q deletion and JBS.

Deletion 2q31.2-q31.3 in a 4-year-old girl with microcephaly and severe mental retardation†

Deletion 2q31.2-q31.3 in a 4-Year-Old Girl With Microcephaly and Severe Mental Retardation Emmanouil Manolakos,* Annalisa Vetro, Konstantinos Kefalas, Loretta Thomaidis, Georgios Aperis, Sotirios Sotiriou, George Kitsos, Martina Merkas, Stavros Sifakis, Ioannis Papoulidis, Thomas Liehr, Orsetta Zuffardi, and Michael B. Petersen Bioiatriki S.A., Laboratory of Genetics, Athens, Greece Dipartimento di Patologia Umana ed Ereditaria, Universita di Pavia, Pavia, Italy Department of Paediatrics, University of Athens, Aglaia Kyriakou Children’s Hospital, Athens, Greece Nephrology Clinic, General Hospital Rhodes, Agioi Apostoloi, Rhodes, Greece Department of Embryology, University of Thessaly, Larissa, Greece Department of Ophthalmology, University of Ioannina, Ioannina, Greece Jena University Hospital, Institute of Human Genetics and Anthropology, Jena, Germany Department of Obstetrics and Gynecology, University Hospital of Heraklion, Crete, Greece Eurogenetica, Laboratory of Genetics, Athens, Greece Department of Genetics, Institute of Child Health, Athens, Greece

A 725 kb deletion at 22q13.1 chromosomal region including SOX10 gene in a boy with a neurologic variant of Waardenburg syndrome type 2

Waardenburg syndrome (WS) is a rare (1/40,000) autosomal dominant disorder resulting from melanocyte defects, with varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair, skin, and inner ear. WS is classified into four clinical subtypes (WS1-S4). Six genes have been identified to be associated with the different subtypes of WS, among which SOX10, which is localized within the region 22q13.1. Lately it has been suggested that whole SOX10 gene deletions can be encountered when testing for WS. In this study we report a case of a 13-year-old boy with a unique de novo 725 kb deletion within the 22q13.1 chromosomal region, including the SOX10 gene and presenting clinical features of a neurologic variant of WS2.

Non‐invasive prenatal screening versus prenatal diagnosis by array comparative genomic hybridization: a comparative retrospective study

To calculate the proportion of array comparative genomic hybridization (aCGH) pathogenic results, that would not be detectable by non‐invasive prenatal screening (NIPS).