Role of FISH on Uncultured Amniocytes for the Diagnosis of Aneuploidies in the Presence of Fetal Anomalies

Objective: To assess the accuracy of fluorescent in situ hybridization (FISH) on amniocytes in fetuses affected by structural malformations suggestive of chromosomal anomalies. Methods: FISH of uncultured amniotic fluid cells and conventional cytogenetic analysis were performed on 48 pregnancies with ultrasonographic (US) evidence of fetal anomalies. The AneuVysion® assay (Vysis) with specific probes for chromosomes 13, 18, 21, X and Y, was used. Amniotic fluid samples were obtained between the 14th and 34th weeks of gestation. Results: In cases with a single abnormal US finding (n = 15), 5 aneuploidies were detected (1 case of trisomy 13 and 4 of trisomy 21). In the group with two or more malformations (n = 33) there were 15 aneuploidies (9 cases of trisomy 18, 2 of trisomy 21, 2 monosomy X, 1 trisomy 13, and 1 triploidy). In this group, conventional cytogenetic analysis revealed two additional chromosomal anomalies not detectable by FISH (1 trisomy 16 mosaic, and a terminal deletion 4p). No sex aneuploidies were observed. Conclusions: The lack of false-positive diagnosis in the FISH analysis in our sample prompts us to consider interphase FISH as a useful tool in pregnancies at high risk for chromosomal aneuploidies. When FISH analysis is normal, the overall risk of chromosomal abnormalities is significantly reduced. However, the finding of two chromosomal anomalies undetectable by AneuVysion® assay confirms the need for conventional chromosome analysis to complement FISH results. Moreover, the results collected here, in agreement with those already reported in the literature, indicate that FISH analysis on uncultured amniocytes can play an important role in counselling and decision-making, especially in cases at risk for aneuploidies, such as those with structural abnormalities at US.

[1]  I. Szűcs,et al.  Rare Case of Exomphalos Complicated with Umbilical Cord Teratoma in a Fetus with Trisomy 13 , 2005, Fetal Diagnosis and Therapy.

[2]  V. Zanardo,et al.  Effects of Ibuprofen and Indomethacin on Urinary Antidiuretic Hormone Excretion in Preterm Infants Treated for Patent Ductus Arteriosus , 2005, Fetal Diagnosis and Therapy.

[3]  B. Gürakan,et al.  Non-Invasive Management of Fetal Goiter during Maternal Treatment of Hyperthyroidism in Grave’s Disease , 2005, Fetal Diagnosis and Therapy.

[4]  D. Chitayat,et al.  Tetrasomy 9p Mosaicism Associated with a Normal Phenotype , 2005, Fetal Diagnosis and Therapy.

[5]  T. Waseda,et al.  Analysis of Renal Artery Hemodynamics in Normal Fetuses Using the Color Doppler Method , 2005, Fetal Diagnosis and Therapy.

[6]  P. Carinci,et al.  Rapid Clearance of mRNA for PLAC1 Gene in Maternal Blood after Delivery , 2004, Fetal Diagnosis and Therapy.

[7]  S. South,et al.  Prenatal Detection of an Interstitial Deletion in 4p15 in a Fetus with an Increased Nuchal Skin Fold Measurement , 2004, Fetal Diagnosis and Therapy.

[8]  R. Chaoui,et al.  Congenitally corrected transposition of the great arteries: clues for prenatal diagnosis , 2004, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[9]  D. Chitayat,et al.  Role of amniotic fluid interphase fluorescence in situ hybridization (FISH) analysis in patient management , 2001, Prenatal diagnosis.

[10]  P. N. Rao,et al.  Prenatal diagnosis using interphase fluorescence in situ hybridization (FISH): 2‐year multi‐center retrospective study and review of the literature , 2001, Prenatal diagnosis.

[11]  W. Piyamongkol,et al.  Fetal loss rate associated with cordocentesis at midgestation. , 2001, American journal of obstetrics and gynecology.

[12]  R. Pike.  Technical and clinical assessment of fluorescence in situ hybridization: An ACMG/ASHG position statement. I. Technical considerations: Test and Technology Transfer Committee , 2000, Genetics in Medicine.

[13]  N. Papantoniou,et al.  Genetic amniocentesis in women 20–34 years old: associated risks , 2000, Prenatal diagnosis.

[14]  E. Pergament,et al.  The clinical application of interphase FISH in prenatal diagnosis , 2000, Prenatal diagnosis.

[15]  K. Nicolaides,et al.  International, collaborative assessment of 146,000 prenatal karyotypes: expected limitations if only chromosome-specific probes and fluorescent in-situ hybridization are used. , 1999, Human reproduction.

[16]  W. Piyamongkol,et al.  Amniocentesis‐Related Fetal Loss: A Cohort Study , 1998, Obstetrics and gynecology.

[17]  W. Piyamongkol,et al.  Amniocentesis-Related Fetal Loss: A Cohort Study , 1998 .

[18]  F. Malone,et al.  Defining the role of fluorescence in situ hybridization on uncultured amniocytes for prenatal diagnosis of aneuploidies. , 1997, American journal of obstetrics and gynecology.

[19]  F. Mitelman.  ISCN 1995 : an international system for human cytogenetic nomenclature (1995) : recommendations of the International Standing Committee on Human Cytogenetic Nomenclature : Memphis, Tennessee, USA, October 9-13, 1994 , 1995 .

[20]  S Campbell,et al.  Ultrasonographically detectable markers of fetal chromosomal abnormalities , 1992, The Lancet.

[21]  P. Jacobs,et al.  A cytogenetic survey of 11,680 newborn infants , 1974, Annals of human genetics.

[22]  P. Jacobs,et al.  Chromosome studies on 3500 newborn male infants. , 1970, Lancet.