Prenatal diagnosis of haemoglobinopathies: our experience of 523 cases

Abstract

Our PD procedure is successful and reliable, and is useful in high-risk areas characterised by molecular heterogeneity.

Prenatal diagnosis of inherited diseases: 20 years’ experience of an Italian Regional Reference Centre

“…Furthermore, in six cases STR preliminary analysis revealed that CV DNA was contaminated by maternal DNA; they included one case of haemophilia (in which the foetus was female), two cases of thalassaemia (in which the paternal mutation was absent) and three cases for which PD was not concluded. In all other cases, including eight twin dichorionic pregnancies, PD was concluded [see also [12][13][14][15]. Finally, in 15 cases, STR analysis revealed non-paternity.…”

“…Analytical procedures for the PD of inherited diseases are very heterogeneous, and laboratories must be equipped with advanced technologies that include: 1) scanning procedures like DHPLC [17] or sequencing, because in more than half the diseases, mutations are scattered throughout the disease-gene [18] and procedures based on restricted panels of mutations have a low detection rate [19]; 2) quantitative PCR or CGH to reveal large gene rearrangements found in CF [19], HA [20], thalassaemia [14], DMD [15], spinocerebellar ataxia [21] and other diseases [22]. In addition, CGH can be used to analyse chromosomal alterations associated with gain or loss of DNA thereby becoming a complementary approach to karyotyping [23]; 3) Southern blot, long PCR or capillary electrophoresis to assess microsatellite expansion typically found in Huntington's disease [24], fragile X syndrome [25], Friedreich's ataxia [26], DM1 [15], and spinocerebellar ataxia [21].…”

“…In addition, the laboratory must be equipped with adequate quality control programmes [30]. For most diseases we used two different analytical procedures (that have invariably given concordant results), including, where available, linkage analysis [12][13][14][15]31]. Finally, the laboratory must be equipped to perform a preliminary analysis of maternal cell contamination and paternity testing (since in most PDs only parental mutations are analysed).…”

“…This is lower than the 4% currently reported [32], which may depend on the preliminary purification of CV that we perform immediately after sampling. Furthermore, in 15 cases, STR analysis revealed non-paternity [see 12,14]. Physicians in our region are involved in multidisciplinary counselling, as required by regional law.…”

“…The procedures for molecular analysis of cystic fibrosis (CF) [12], haemophilia A (HA) and B (HB) [13], thalassaemia and haemoglobinopathies [14], Duchenne/Becker dystrophies (DMD), myotonic dystrophy type I (DM1) and spinal muscular atrophy [15] are detailed in other articles of this issue of CCLM. Protocols for the molecular or biochemical PD of other inherited diseases are available on request.…”