A minimal set of SNPs for the noninvasive prenatal diagnosis of ß-thalassaemia.

ß-thalassaemia is one of the commonest autosomal recessive single-gene disorders worldwide. Prenatal tests use invasive methods, posing a risk for the pregnancy itself. Development of a noninvasive prenatal diagnostic method is, therefore, of paramount importance. The aim of the present study is to identify high-heterozygote informative single-nucleotide polymorphisms (SNPs), suitable for the development of noninvasive prenatal diagnosis (NIPD) of ß-thalassaemia. SNP genotyping analysis was performed on 75 random samples from the Cypriot population for 140 SNPs across the ß-globin cluster. Shortlisted, highly heterozygous SNPs were then examined in 101 carrier families for their applicability in the noninvasive detection of paternally inherited alleles. Forty-nine SNPs displayed more than 6% heterozygosity and were selected for NIPD analysis, revealing 72.28% of the carrier families eligible for qualitative SNP-based NIPD, and 92% for quantitative detection. Moreover, inference of haplotypes showed predominant haplotypes and many subhaplotypes with sufficient prevalence for diagnostic exploitation. SNP-based analyses are sensitive and specific for the detection of the paternally inherited allele in maternal plasma. This study provides proof of concept for this approach, highlighting its superiority to NIPD based on single markers and thus providing a blueprint for the general development of noninvasive prenatal diagnostic assays for ß-thalassaemia.

De novo interstitial duplication of the 15q11.2-q14 PWS/AS region of maternal origin: Clinical description, array CGH analysis, and review of the literature.

The 15q11-q13 PWS/AS critical region involves genes that are characterized by genomic imprinting. Multiple repeat elements within the region mediate rearrangements, including interstitial duplications, interstitial triplications, and supernumerary isodicentric marker chromosomes, as well as the deletions that cause Prader-Willi syndrome (PWS) and Angelman syndrome (AS). Recently, duplications of maternal origin concerning the same critical region have been implicated in autism spectrum disorders (ASD). We present a 6-month-old girl carrying a de novo duplication of maternal origin of the 15q11.2-q14 PWS/AS region (17.73 Mb in size) [46,XX,dup(15)(q11.2-q14)] detected with a high-resolution microarray-based comparative genomic hybridization (array-CGH). The patient is characterized by severe hypotonia, obesity, microstomia, long eyelashes, hirsutism, microretrognathia, short nose, severe psychomotor retardation, and multiple episodes of drug-resistant epileptic seizures, while her brain magnetic resonance imaging (MRI) documented partial corpus callosum dysplasia. In our patient the duplicated region is quite large extending beyond the Prader-Willi-Angelman critical region (PWACR), containing a number of genes that have been shown to be involved in ASD, exhibiting a severe phenotype, beyond the typical PWS/AS clinical manifestations. Reporting of similar well-characterized clinical cases with clearly delineated breakpoints of the duplicated region will clarify the contribution of specific genes to the phenotype.

A novel p.Arg970X mutation in the last exon of the CDKL5 gene resulting in late-onset seizure disorder.

Classic Rett Syndrome (RS) is a neurodevelopmental disorder due to mutations in the MECP2 gene in Xq28. Atypical RS with severe early-onset encephalopathy and therapy-resistant epilepsy can be due to mutations in the CDKL5 (Cyclin-Dependent Kinase-like 5) gene in Xp22. We here report a 14-year-old female with a RS-like clinical picture, and well-controlled seizures. MECP2 gene testing was negative, but subsequent sequencing of the CDKL5 gene revealed the c. 2908 C>T nonsense mutation (p.Arg970X) in the last exon, not previously described in other patients or controls. The less severe phenotype might be due to the position of the mutation in the last exon of the CDKL5 gene.

Estimating the population burden of injuries: a comparison of household surveys and emergency department surveillance.

BACKGROUND: Injuries represent an important public health problem but their incidence is difficult to estimate. METHODS: We conducted a population-based household survey in Greece covering 4079 interviewed individuals. The interviewees reported, for themselves and for cohabitating adults (age 15 years and older; n = 7157), injuries that occurred during the preceding year. Major injuries were defined as those requiring contact with a health institution. We compared these survey data with data obtained through a national Emergency Department Injury Surveillance System (EDISS). RESULTS: For the month closest to the survey interview, the incidence reported for the responders was 5.9 per 100 person-year, whereas the incidence for cohabitating adults was 3.7 per 100 person-years. These incidence rates declined for months more remote to the interview. Comparison of survey and EDISS data suggested that survey reporting was less accurate for nontraffic-related injuries. Taking into account possible recall and telescoping biases, the best survey estimate of the national annual number of major injuries is 525,000 (5.9 per 100 person-year), whereas the EDISS data yielded an estimate of 1,150,000 major injuries (12.9 per 100 person-years) CONCLUSIONS: Comparison of survey and EDISS data systems provides quantitative assessment of accuracy of the survey data in relation to time of injury before report date, to severity of injury, and to whether the injury is to the interviewee or to a cohabitant. The 2 systems could be used in a complementary way, although EDISS generates information that is medically more accurate and is a more cost-effective data collection system.