Early prenatal diagnosis of genetic microcephaly

We report a new case of prenatal diagnosis of recessive microcephaly by ultrasound examination allowing termination of pregnancy at 25 weeks gestation.     

Pericentric inversion of chromosome 19: prenatal diagnosis and genetic counselling

During prenatal diagnosis for advanced maternal age, a pericentric inversion of a chromosome 19 was detected in a male fetus. The inversion was familial, transmitted to the fetus by the phenotypically normal mother. The pregnancy resulted in a term birth of a phenotypically normal male infant. Inversion 19 appears to be a rare abnormality with only seven families reported thus far including ours. Infants with duplication deficiencies for chromosome 19 have not been reported in these families. This may suggest an apparent suppression of crossing over and recombination within the inverted segment of chromosome 19 during meiosis.     

Molecular genetic prenatal diagnosis for a case of autosomal recessive spondylocostal dysostosis

Autosomal recessive spondylocostal dysostosis type 1 (ARSCD1) is a member of the heterogeneous group of disorders termed the spondylocostal dysostoses that are characterized by multiple vertebral segmentation defects and rib anomalies. In these patients, the entire vertebral column is malformed and is replaced by multiple hemivertebrae giving rise to truncal shortening, abdominal protrusion and non-progressive spinal curvature. Genetic studies have shown that some cases of ARSCD are due to mutations in the somitogenesis gene, Delta-like 3 (DLL3), that encodes a ligand for the Notch signalling pathway—ARSCD type 1. To date, 17 different DLL3 gene mutations have been reported. A consanguineous family of Turkish origin with ARSCD type 1 due to a homozygous DLL3 mutation requested genetic prenatal diagnosis. Using DNA from a chorionic villus sample, both linkage analysis of the DLL3/19q region and direct sequencing for the familial mutation demonstrated that the unborn fetus was an unaffected carrier. This is the first case of molecular genetic prenatal diagnosis in any form of SCD. Copyright © 2003 John Wiley & Sons, Ltd.     

Carbamoyl phosphate synthetase I deficiency: molecular genetic findings and prenatal diagnosis

We report a Japanese boy who died at Day 28 of life because of severe carbamoyl phosphate synthetase I (CPS1) deficiency that was proven by enzyme assay. By analysis of cDNA and genomic DNA, he was shown to be a compound heterozygote with two point mutations of the CPS1 gene, 840G>C leading to an aberrant splicing and 1123C>T (predicting Q375X). The 840G>C was a mutation described in another Japanese family. Since his parents carried each mutation heterozygously, we performed prenatal diagnosis at 16 weeks of his mother's next gestation by multiplex PCR and melting curve analysis in a single capillary containing two-color fluorescent (LC-Red 640 and LC-Red 705) probes on LightCycler. We analyzed genomic DNA extracted from amniotic cells and found that the fetus was homozygous for the wild-type alleles. At term a healthy girl was born without hyperammonemia. Copyright © 2001 John Wiley & Sons, Ltd.