Background: Chronic lung diseases are a major issue in public health. A serial pulmonary assessment using imaging techniques free of ionizing radiation and which provides early information on local function impairment would therefore be a considerably important development. Magnetic resonance imaging (MRI) is a powerful tool for the static and dynamic imaging of many organs. Its application in lung imaging however, has been limited due to the low water content of the lung and the artefacts evident at air-tissue interfaces. Many attempts have been made to visualize local ventilation using the inhalation of hyperpolarized gases or gadolinium aerosol responding to MRI. None of these methods are applicable for broad clinical use as they require specific equipment.

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In all known congenital imprinting disorders an association with aberrant methylation or mutations at specific loci was well established. However, several patients with transient neonatal diabetes mellitus (TNDM), Silver-Russell syndrome (SRS) and Beckwith-Wiedemann syndrome (BWS) exhibiting multilocus hypomethylation (MLH) have meanwhile been described. Whereas TNDM patients with MLH show clinical symptoms different from carriers with isolated 6q24 aberrations, MLH carriers diagnosed as BWS or SRS present only the syndrome-specific features. Interestingly, SRS and BWS patients with nearly identical MLH patterns in leukocytes have been identified. We now report on the molecular findings in DNA in three SRS patients with hypomethylation of both 11p15 imprinted control regions (ICRs) in leukocytes. One patient was a monozygotic (MZ) twin, another was a triplet. While the hypomethylation affected both oppositely imprinted 11p15 ICRs in leukocytes, in buccal swab DNA only the ICR1 hypomethylation was visible in two of our patients. In the non-affected MZ twin of one of these patients, aberrant methylation was also present in leukocytes but neither in buccal swab DNA nor in skin fibroblasts. Despite mutation screening of several factors involved in establishment and maintenance of methylation marks including ZFP57, MBD3, DNMT1 and DNMT3L the molecular clue for the ICR1/ICR2 hypomethylation in our patients remained unclear. Furthermore, the reason for the development of the specific SRS phenotype is not obvious. In conclusion, our data reflect the broad range of epimutations in SRS and illustrate that an extensive molecular and clinical characterization of patients is necessary.

121 healthy premature born infants and full term newborns (corrected gestational age 29 to 45 weeks, weight at investigation 1070 to 3750 g) were investigated by pulsed Doppler sonography with a 5 MHz transducer. In all infants pulsed Doppler recordings were obtained from the internal carotid arteries (ICA), the basilar artery (BA) and both anterior cerebral arteries (ACA). From the flow profile the maximal systolic velocity (Vs), the endsystolic velocity (Ves) and the enddiastolic velocity (Ved), the time average velocity (TAV) and the time average maximal velocity (TAMX) as well as the resistance-index (RI) and the pulsatility-index (PI) were measured. For all parameters the relationship to the gestational age was analysed and normal values were established. There was a linear increase of all flow velocities with increasing gestational age. Vs in the ICA was about 20% higher than in the ACA and BA whereas Ves and Ved were not significantly different in the three arteries. The TAV in the ICA was 9% higher than in the ACA and 15% higher than in the BA. The TAMX in the ICA was 10% higher than in the ACA and 14% higher than in the BA. In contrast to the increase of the flow velocities neither the RI nor the PI showed a significant age dependency. For the RI in the ICA 0.77 +/- 0.08, in the ACA 0.73 +/- 0.08 and in the BA 0.72 +/- 0.09 were measured. The PI in the ICA was 3.0 +/- 0.08, in the ACA 2.7 +/- 0.09 and in the BA 2.7 +/- 0.7.(ABSTRACT TRUNCATED AT 250 WORDS)

Two disorders, periventricular nodular heterotopia (PVNH) and a group of skeletal dysplasias belonging to the oto-palato-digital (OPD) spectrum, are caused by FLNA mutations. They are considered mutually exclusive because of the different presumed effects of the respective FLNA gene mutations, leading to loss of function (PVNH) and gain of function (OPD), respectively. We describe here the first patient manifesting PVNH in combination with frontometaphyseal dysplasia, a skeletal dysplasia of the OPD-spectrum. A novel de novo mutation, 7315C-->A in exon 45 of the FLNA gene, was identified. It leads to two aberrant transcripts, one full-length transcript with the point mutation causing a substitution of a highly conserved leucine residue (L2439M) and a second shortened transcript lacking 21 bp due to the creation of an ectopic splice donor site in exon 45. We propose that the dual phenotype is caused by two functionally different, aberrant filamin A proteins and therefore represents an exceptional model case of allelic gain-of-function and loss-of-function phenotypes due to a single mutational event.