A novel ß(0)-thalassemia frameshift mutation: [HBB:c.216delT].

A 33-year-old adult male of Greek ethnicity, with hematological indices suggesting ß(0)-thalassemia (ß(0)-thal) trait, was investigated for HBB gene mutations in the course of preparation for preimplantation genetic diagnosis (PGD). Application of a routine diagnostic protocol, consisting of sequence analysis of the HBB gene, coupled to multiplex ligation-dependent probe amplification (MLPA), identified a single nucleotide deletion (-T) at codon 72 [HBB: c.216delT], leading to a novel pathogenic frameshift and protein-truncating ß(0)-thal mutation (p.Phe72LeufsX18).

Uncovering recurrent microdeletion syndromes and subtelomeric deletions/duplications through non-selective application of a MLPA-based extended prenatal panel in routine prenatal diagnosis.

OBJECTIVE: To present the application of multiplex ligation-dependent probe amplification (MLPA)-based screening approach in 1550 typical prenatal cases, for the simultaneous targeted detection of 23 recurrent microdeletion syndromes as well as subtelomeric copy number assessment for all chromosomes and discuss the implications in routine prenatal chromosomal diagnosis (PCD). METHODS: Following amniocentesis or chorionic villus sampling, samples were processed for routine karyotype analysis while DNA was extracted in parallel for MLPA analysis. When necessary, parental samples were analyzed to determine the inheritance of the detected aberrations. RESULTS: This panel has been applied since 2006 in 1550 prenatal samples, referred for routine karyotype analysis, with (16.1%) or without (77.7%) ultrasound (US) findings. We identified eight fetuses with pathological genomic abnormalities (approximately 1 in 193), five of which had as sole indication advanced maternal age (1 in 240). In two cases an abnormality was suspected from karyotype analysis, while the remaining six cases would have otherwise remained totally undetected. CONCLUSIONS: Our data represent the largest published series involving this type of genomic analysis in routine prenatal diagnosis, without indication bias. The panel increases significantly the diagnostic yield of conventional PCD and does not pose interpretation problems.