Spectrum of PEX1 and PEX6 variants in Heimler syndrome

Heimler syndrome (HS) consists of recessively inherited sensorineural hearing loss, amelogenesis imperfecta (AI) and nail abnormalities, with or without visual defects. Recently HS was shown to result from hypomorphic mutations in PEX1 or PEX6, both previously implicated in Zellweger Syndrome Spectrum Disorders (ZSSD). ZSSD are a group of conditions consisting of craniofacial and neurological abnormalities, sensory defects and multi-organ dysfunction. The finding of HS-causing mutations in PEX1 and PEX6 shows that HS represents the mild end of the ZSSD spectrum, though these conditions were previously thought to be distinct nosological entities. Here, we present six further HS families, five with PEX6 variants and one with PEX1 variants, and show the patterns of Pex1, Pex14 and Pex6 immunoreactivity in the mouse retina. While Ratbi et al. found more HS-causing mutations in PEX1 than in PEX6, as is the case for ZSSD, in this cohort PEX6 variants predominate, suggesting both genes play a significant role in HS. The PEX6 variant c.1802G>A, p.(R601Q), reported previously in compound heterozygous state in one HS and three ZSSD cases, was found in compound heterozygous state in three HS families. Haplotype analysis suggests a common founder variant. All families segregated at least one missense variant, consistent with the hypothesis that HS results from genotypes including milder hypomorphic alleles. The clinical overlap of HS with the more common Usher syndrome and lack of peroxisomal abnormalities on plasma screening suggest that HS may be under-diagnosed. Recognition of AI is key to the accurate diagnosis of HS

Maternal Serum Triple Marker Levels in Immigrants to Israel from Ethiopia

&lt;i&gt;Objectives:&lt;/i&gt; To determine if Ethiopian immigrants have similar triple marker levels as the general Israeli population. &lt;i&gt;Material and Methods:&lt;/i&gt; Second-trimester maternal serum results on 346 Ethiopians were obtained from records of 36,309 women. Two series were constructed for comparison among patients screened between 2000 and 2001 (‘old group’) and 2005 and 2007 (‘new group’). &lt;i&gt;Results:&lt;/i&gt; The median and 95% confidence intervals (CI) were: α-fetoprotein (AFP) 1.080 multiples of median (MoM) (95% CI 1.03–1.13); human chorionic gonadotrophin (hCG) 0.895 MoM (95% CI 0.82–0.97), and unconjugated estriol (uE&lt;sup&gt;3&lt;/sup&gt;) 1.050 MoM (95% CI 1.00–1.10). The differences between the AFP and hCG medians for the old and new series were not statistically significant (p = 0.06 and 0.20) whilst the uE&lt;sup&gt;3&lt;/sup&gt; difference was significant (p = 0.04). There was a general tendency for the levels to be closer to 1 MoM over time. &lt;i&gt;Conclusions:&lt;/i&gt; Triple marker serum levels of AFP and hCG among Ethiopian patients may need to be slightly corrected, particularly for hCG.</jats:p