Variations in the Difference between Mean Sea Level measured either side of Cape Hatteras and Their Relation to the North Atlantic Oscillation

We consider the extent to which the difference in mean sea level (MSL) measured on the North American Atlantic coast either side of Cape Hatteras varies as a consequence of dynamical changes in the ocean caused by fluctuations in the North Atlantic Oscillation (NAO). From analysis of tide gauge data, we know that changes in MSL-difference and NAO index are correlated on decadal to century timescales enabling a scale factor of MSL-difference change per unit change in NAO index to be estimated. Changes in trend in the NAO index have been small during the past few centuries (when measured using windows of order 60–120 years). Therefore, if the same scale factor applies through this period of time, the corresponding changes in trend in MSL-difference for the past few centuries should also have been small. It is suggested thereby that the sea level records for recent centuries obtained from salt marshes (adjusted for long-term vertical land movements) should have essentially the same NAO-driven trends south and north of Cape Hatteras, only differing due to contributions from other processes such as changes in the Meridional Overturning Circulation or ‘geophysical fingerprints’. The salt marsh data evidently support this interpretation within their uncertainties for the past few centuries, and perhaps even for the past millennium. Recommendations are made on how greater insight might be obtained by acquiring more measurements and by improved modelling of the sea level response to wind along the shelf

Identification of entire LMX1B gene deletions in nail patella syndrome: evidence for haploinsufficiency as the main pathogenic mechanism underlying dominant inheritance in man.

Contains fulltext : 69895.pdf (publisher's version ) (Closed access)Heterozygous mutations in the LMX1B gene cause nail patella syndrome (NPS) that is associated with nail and skeletal malformations, nephropathy, and glaucoma. Previous phenotype studies of Lmx1b null mice revealed dorsal limb and renal anomalies similar to human NPS, which contributed to the identification of heterozygous mutations in this LIM-homeodomain protein LMX1B as the genetic defect responsible for NPS. Despite advanced insight into the role of the Lmx1b transcription factor in a broad range of animal developmental programs, the pathogenic mechanism underlying dominant inheritance of NPS in man remained unclear. Here, we describe for the first time the detection of two entire LMX1B gene deletions and one smaller exonic LMX1B deletion by multiplex ligation-dependent probe amplification (MLPA) in a series of eight unrelated families with classical features of NPS in whom no pathogenic LMX1B mutation was found by sequence analysis. The identification of entire LMX1B deletions strongly confirms that haploinsufficiency is the principal pathogenetic mechanism of NPS and suggests a difference in dosage sensitivity for this gene between mice and man

Genotype-phenotype studies in nail-patella syndrome show that LMX1B mutation location is involved in the risk of developing nephropathy.

Contains fulltext : 47792.pdf (publisher's version ) (Closed access)Nail-patella syndrome (NPS) is characterized by developmental defects of dorsal limb structures, nephropathy, and glaucoma and is caused by heterozygous mutations in the LIM homeodomain transcription factor LMX1B. In order to identify possible genotype-phenotype correlations, we performed LMX1B mutation analysis and comprehensive investigations of limb, renal, ocular, and audiological characteristics in 106 subjects from 32 NPS families. Remarkable phenotypic variability at the individual, intrafamilial, and interfamilial level was observed for different NPS manifestations. Quantitative urinanalysis revealed proteinuria in 21.3% of individuals. Microalbuminuria was detected in 21.7% of subjects without overt proteinuria. Interestingly, nephropathy appeared significantly more frequent in females. A significant association was established between the presence of clinically relevant renal involvement in an NPS patient and a positive family history of nephropathy. We identified normal-tension glaucoma (NTG) and sensorineural hearing impairment as new symptoms associated with NPS. Sequencing of LMX1B revealed 18 different mutations, including six novel variants, in 28 families. Individuals with an LMX1B mutation located in the homeodomain showed significantly more frequent and higher values of proteinuria compared to subjects carrying mutations in the LIM domains. No clear genotype-phenotype association was apparent for extrarenal manifestations. This is the first study indicating that family history of nephropathy and mutation location might be important in precipitating individual risks for developing NPS renal disease. We suggest that the NPS phenotype is broader than previously described and that NTG and hearing impairment are part of NPS. Further studies on modifier factors are needed to understand the mechanisms underlying phenotypic heterogeneity