ABSTRACT
OBJECTIVE: To investigate the performance of first-trimester screening for chromosomal abnormalities by integrated application of nuchal translucency thickness (NT), nasal bone (NB), tricuspid regurgitation (TR) and ductus venosus (DV) flow combined with maternal serum free ß-human chorionic gonadotropin (fß-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at a one-stop clinic for assessment of risk (OSCAR). METHODS: In total, 13,706 fetuses in 13,437 pregnancies were screened for chromosomal abnormalities during a period of 5 years. Maternal serum biochemical markers and maternal age were evaluated in combination with NT, NT + NB, NT + NB + TR, and NT + NB + TR + DV flow data in 8581, 242, 236 and 4647 fetuses, respectively. RESULTS: In total, 51 chromosomal abnormalities were identified in the study population, including 33 cases of trisomy 21, eight of trisomy 18, six of sex chromosome abnormality, one of triploidy and three of other unbalanced abnormalities. The detection rate and false-positive rate (FPR) for trisomy 21 were 93.8% and 4.84%, respectively, using biochemical markers and NT, and 100% and 3.4%, respectively, using biochemical markers, NT, NB, TR and DV flow. CONCLUSION: While risk assessment using combined biochemical markers and NT measurement has an acceptable screening performance, it can be improved by the integrated evaluation of secondary ultrasound markers of NB, TR and DV flow. This enhanced approach would decrease the FPR from 4.8 % to 3.4 %, leading to a lower number of unnecessary invasive diagnostic tests and subsequent complications, while maintaining the maximum level of detection rate. Pre- and post-test genetic counseling is of paramount importance in either approach.
Subject(s)
Chorionic Gonadotropin, beta Subunit, Human/blood , Chromosome Disorders/diagnosis , Down Syndrome/diagnosis , Nasal Bone/diagnostic imaging , Pregnancy-Associated Plasma Protein-A/metabolism , Tricuspid Valve Insufficiency/diagnostic imaging , Trisomy/diagnosis , Ultrasonography, Prenatal , Adolescent , Adult , Biomarkers/blood , Chromosome Disorders/embryology , Chromosome Disorders/pathology , Chromosomes, Human, Pair 13 , Down Syndrome/embryology , Down Syndrome/pathology , Female , Humans , Maternal Age , Middle Aged , Nasal Bone/embryology , Nasal Bone/pathology , Nuchal Translucency Measurement , Pregnancy , Pregnancy Trimester, First , Prospective Studies , Risk Assessment , Tricuspid Valve Insufficiency/embryology , Tricuspid Valve Insufficiency/physiopathology , Triploidy , Trisomy/pathology , Trisomy 13 Syndrome , Young AdultABSTRACT
17-ß-hydroxysteroid dehydrogenase type 3 (17-ß-HSD 3) deficiency is an autosomal recessive form of 46,XY disorder of sex development (DSD). To date, a total of 27 HSD17B3 gene mutations have been described in 46,XY patients exhibiting different phenotypes at birth and virilization at puberty, sometimes in association with gynecomastia. Herein, we investigate the 46,XY DSD in an Iranian family consisting of 7 siblings, 3 of which are affected and virilized at puberty. We clinically characterized these patients and performed direct DNA sequencing of the steroid 5-α-reductase type 2 (SRD5A2) and the HSD17B3 gene, respectively. We identified a homozygous mutation in the HSD17B3 gene (R80W; c.238C>G) in all affected siblings. No mutation was detected in the SRD5A2 gene. The detected mutation in the HSD17B3 gene was previously described in a newborn child, who died from other congenital malformations, and in a 12-year-old girl. Hence, our report adds novel value to the phenotype classification of 17-ß-HSD 3 deficiency.
