We have made evident the possibility of detecting an inherited paternal mutation in a non-invasive way at the 13t(hr) weeks of pregnancy. This methodology could be very useful in cases of paternally inherited dominant disorders. The technical improvements in fetal DNA detection and analysis might lead to the development of new applications in the non-invasive prenatal diagnosis field.

R etinitis pigmentosa (RP), which occurs in about one in 3000-7000 people in Spain, is inherited in an autosomal dominant manner in 12% of cases, in an autosomal recessive way in 39%, and in an X linked manner in 4% of cases. This leaves 41% of RP cases with a simplex form and 4% in which the transmission pattern is unclear.

The discovery of fetal DNA in maternal plasma from early pregnancies has led to new opportunities for clinical application. In the last few years there have been numerous reported applications, mainly fetal gender and RhD genotyping. The prenatal diagnosis of some inherited genetic diseases such as Huntington disease is also very frequently required in the prenatal diagnosis routine. We have successfully diagnosed, with a non-invasive procedure, an unaffected HD fetus at the 13th week of gestation using fetal DNA from maternal plasma and the quantitative fluorescent PCR method, which is one of the most sensitive ways to detect fetal DNA in maternal plasma at such an early time of gestation.

QF-PCR represents a useful and reliable tool to diagnose aneuploidies in spontaneous miscarriages. It provides information about parental and meiotic origin of anomaly, allowing an appropriate genetic counselling.

The RPGR (retinitis pigmentosa GTPase regulator) gene has been shown to be mutated in 10-20% of patients with X-linked retinitis pigmentosa (XLRP), a severe form of inherited progressive retinal degeneration. A total of 29 different RPGR mutations have been identified in northern European and United States patients. We have performed mutation analysis of the RPGR gene in a cohort of 49 southern European males affected with XLRP. By multiplex SSCA and automatic direct sequencing of all 19 RPGR exons, seven different and novel mutations were identified in eight of the 49 families; these include three splice site mutations, two microdeletions, and two missense mutations. RNA analysis showed that the three splice site defects resulted in the generation of aberrant RPGR transcripts. Six of these mutations were detected in the conserved amino-terminal region of RPGR protein, containing tandem repeats homologous to the RCC1 protein, a guanine nucleotide-exchange factor for RanGTPase. Several exonic and intronic sequence variations were also detected. None of the RPGR mutations reported in other populations were identified in our series. Our results are consistent with the notions of heterogeneity and minority causation of XLRP by mutations in RPGR in Caucasian populations.