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Contains fulltext : 52357.pdf (Publisher’s version ) (Closed access) L1 elements are autonomous retrotransposons that can cause hereditary diseases. We have previously identified a full-length L1 insertion in the CHM (choroideremia) gene of a patient with choroideremia, an X-linked progressive eye disease. Because this L1 element, designated L1(CHM), contains two 3'-transductions, we were able to delineate a retrotransposition path in which a precursor L1 on chromosome 10p15 or 18p11 retrotransposed to chromosome 6p21 and subsequently to the CHM gene on chromosome Xq21. A cell culture retrotransposition assay showed that L1(CHM) is one of the most active L1 elements in the human genome. Most importantly, analysis of genomic DNA from the CHM patient's relatives indicated somatic and germ-line mosaicism for the L1 insertion in his mother. These findings provide evidence that L1 retrotransposition can occur very early in human embryonic development.

Pseudoxanthoma elasticum (PXE) is a hereditary disorder of connective tissue with skin, cardiovascular, and visual involvement. In familial cases, PXE usually segregates in an autosomal recessive fashion. The aim of this manuscript is to describe an efficient strategy for DNA diagnosis of PXE. The two most frequent mutations, R1141X and an ABCC6 del exons 23-29, as well as a core set of mutations, were identified by restriction enzyme digestion and size separation on agarose gels. Next, in the remaining patient group in which only one or no mutant allele was found, the complete coding sequence was analyzed using denaturing high-performance liquid chromatography (dHPLC). All variations found were confirmed by direct DNA sequencing. Finally, Southern blot was used to investigate the potential presence of small or large deletions. Twenty different mutations, including two novel mutations in the ABCC6 gene, were identified in 80.3% of the 76 patients, and 58.6% of the 152 ABCC6 alleles analyzed. With this strategy, 70 (78.7%) out of 89 mutant alleles could be detected within a week. We conclude that this strategy leads to both reliable and time-saving screening for mutations in the ABCC6 gene in sporadic cases and in families with PXE.

We present 5 unrelated patients, 3 boys and 2 girls, with Pfeiffer syndrome (PS) type 2, They all had cloverleaf skull, severe proptosis, ankylosis of the elbows, broad thumbs and/or broad halluces and variable accompanying anomalies, We review the literature on all subtypes of PS, Most patients with PS type 2 died shortly after birth, Causes of death include pulmonary problems, brain abnormalities, prematurity and post-operative complications. DNA studies were performed in 3 of the 5 patients, Two of them showed a 1036T --> C mutation in the fibroblast growth factor receptor 2 (FGFR2) gene, that was earlier reported in PS and in Crouzon syndrome, Probably most, if not all, PS type 2 cases are caused by a de novo mutation in the FGFR2 gene or in another, yet unidentified gene, To date all type 2 cases have been non-familial. A low recurrence risk for parents can be advised, (C) 1998 Wiley-Liss, Inc.