Sanger sequencing solved a cryptic case of severe alpha₁-antitrypsin deficiency.

Aims: Alpha(1)-antitrypsin deficiency (AATD) is a clinically under-diagnosed genetic disorder that originates from deleterious mutations in the alpha(1)-antitrypsin (AAT) gene, SERPINA1. Severe deficiency is associated with significant pulmonary and hepatic malfunctions. Conventional clinical diagnosis involves the evaluation of serum AAT level and detection of diseased protein isoforms.

Polyalanine expansion in the ZIC3 gene leading to X-linked heterotaxy with VACTERL association: a new polyalanine disorder?

Background: The VACTERL association is a non-random association of congenital defects with an unknown aetiology in the majority of patients.

Methods: A male newborn is reported with features of the VACTERL association, including anal atresia, laryngeal and oesophageal atresia with tracheo-oesophageal fistula, dextroposition of the heart with persistent left superior vena cava, and unilateral multicystic kidney. As the clinical picture of this patient overlaps with that of X-linked heterotaxy caused by ZIC3 mutations, the ZIC3 coding region was sequenced.

Origin of amnion and implications for evaluation of the fetal genotype in cases of mosaicism.

Objective: To investigate presence of trisomy in amniotic epithelium (uncultured amnion) and mesenchyme (cultured amnion) from mosaic cases to understand the origins of these tissues and their relationship to pregnancy outcome.

Methods: Polymerase chain reaction (PCR) of microsatellite loci was used to determine the presence of trisomy (of meiotic origin only) in amnion samples from 33 placentas previously ascertained because of a prenatal diagnosis of trisomy mosaicism that was predominantly confined to the placental tissues.

Results: In 16 (48%) of 33 cases, trisomy was confirmed to be present by molecular analysis of uncultured amnion.

Two cases of confined placental mosaicism for chromosome 4, including one with maternal uniparental disomy.

Two cases of trisomy 4 mosaicism are reported including one with molecularly confirmed uniparental disomy (UPD) of chromosome 4. Cytogenetic analysis of a chorionic villus sample (CVS) in Case 1 showed complete trisomy 4 in trophoblast and diploidy in chorionic stroma. Amniotic fluid analysis demonstrated a 46,XX complement.

Recurrent trisomy 21 in a couple with a child presenting trisomy 21 mosaicism and maternal uniparental disomy for chromosome 21 in the euploid cell line.

Recurrence of trisomy 21 was observed in a family in which both parents had a normal chromosome complement. Mosaic trisomy 21 was found in a blood karyotype of the first child, a second pregnancy ended in spontaneous abortion, and a full trisomy 21 was found at prenatal diagnosis of the third pregnancy of this same couple. Although recurrent trisomy 21 may be due to chance, the possibility of germline mosaicism for trisomy 21 in one of the parents has important implications for recurrence risk.