Disruption of the Catechol-O-methyltransferase (COMT) gene has been shown to be involved in pre-eclampsia (PE). To investigate whether two promoters of the COMT gene are differentially regulated by methylation in PE patients, we have analyzed the genomic DNA extracted from placenta (cases n = 16; controls n = 21), maternal peripheral blood (cases n = 4; controls n = 6) and umbilical cord blood (cases n = 8; controls n = 8) of women with PE and women with normal pregnancy. Bisulfite sequencing identified the predominantly unmethylated MB-COMT promoter in placenta, maternal peripheral blood and umbilical cord blood samples (PE and control). Subsequent quantitative MassArray data confirmed a significant tissue-specific hypomethylation of the S-COMT promoter in placenta (mean = 28.6%) when compared with its densely methylated patterns in blood samples (mean = 74.5%, P < 0.001), consistent with the sequencing data. However, no PE-specific methylation difference was found between cases and controls either in placenta or in blood samples. Moreover, none of the clinical characteristics had an effect on the methylation status of the S-COMT promoter. This study does not support a causal link between methylation regulation of COMT promoters and PE. However, the observed placenta-specific S-COMT promoter may be a potential marker for early prediction of PE in maternal plasma, although this remains to be further evaluated.

MN1 C‐terminal truncation (MCTT) syndrome is a newly recognized neurodevelopmental disorder due to heterozygous gain‐of‐function C‐terminal truncating mutations clustering in the last or penultimate exon of MN1 gene (MIM: 156100). Up to date, only 25 affected patients have been reported. Here, we report a 2‐year‐old Chinese girl with MCTT syndrome. The girl presented with the characteristic features of the syndrome, including global developmental delay (GDD), facial dysmorphism and hearing impairment. Notably, the patient did not have other frequently observed symptoms such as hypotonia, cranial or brain abnormalities, indicating variability of the phenotype of patients with MN1 C‐terminal truncating mutations. Trio whole‐exome sequencing revealed a novel de novo heterozygous nonsense variant in the extreme 3′ region of penultimate exon of MN1 (NM_002430.3: c.3743G > A, p.Trp1248*). This rare truncating variant was classified as pathogenic due to its predicted gain‐of‐function effect, given that the gain‐of‐function MN1 truncating variants producing C‐terminally truncated proteins have been confirmed to cause the recognizable syndrome. Additionally, a systematic review of previously reported MN1 variants including C‐terminal truncating variants and N‐terminal truncating variants shows that different location of MN1 truncating variants causes two distinct clinical subtypes. To our knowledge, this is the first reported case of MCTT syndrome caused by a novel MN1 C‐terminal truncating variant in a Chinese population, which enriched the mutation spectrum of MN1 gene and further supporting the association of the novel MCTT syndrome with MN1 C‐terminal truncating variants.

No abstract

No abstract

No abstract