Brask Kidd (cherryiran28)

We report a patient with profound congenital hypotonia, central hypoventilation, poor visual behaviour with retinal hypopigmentation, and significantly decreased mitochondrial respiratory chain complex I activity in muscle, who died at 7 months of age having made minimal developmental progress. Biallelic predicted truncating P4HTM variants were identified following trio whole-genome sequencing, consistent with a diagnosis of hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy and eye abnormalities (HIDEA) syndrome. CA074methylester Very few patients with HIDEA syndrome have been reported previously and mitochondrial abnormalities were observed in three of four previous cases who had a muscle biopsy, suggesting the possibility that HIDEA syndrome represents a primary mitochondrial disorder. P4HTM encodes a transmembrane prolyl 4-hydroxylase with putative targets including hypoxia inducible factors, RNA polymerase II and activating transcription factor 4, which has been implicated in the integrated stress response observed in cell and animal models of mitochondrial disease, and may explain the mitochondrial dysfunction observed in HIDEA syndrome.Germline variants that affect the proofreading activity of polymerases epsilon (POLE) and delta (POLD1) predispose to colorectal adenomas and carcinomas, among other cancers. All cancer-associated pathogenic variants reported to date consist of non-disruptive genetic changes affecting the sequence that codifies the exonuclease domain (ED). Generally, disruptive (frameshift, stop-gain) POLE and POLD1 variants and missense variants outside the ED do not predispose to cancer. However, this statement may not be true for some, very specific variants that would indirectly affect the proofreading activity of the corresponding polymerase. We evaluated, by using multiple approaches, the possibility that POLD1 c.883G>A; p.(Val295Met), -a variant located 9 amino acids upstream the ED and present in ~0.25% of hereditary cancer patients-, affects POLD1 proofreading activity. Our findings show cumulative evidence that support no alteration of the proofreading activity and lack of association with cancer. The variant is classified as likely benign according to the ACMG/AMP guidelines.Mild cognitive impairment (MCI) is common in patients with hypertension. Prevalence estimates of MCI in hypertensive patients are needed to guide both public health and clinical decision making. A literature search was conducted in four databases, including PubMed, Embase, Cochrane Library, and Web of Science, from their inception to February 2021. The methodological quality assessment used the risk of bias tool. The pooled prevalence of MCI in hypertensive patients was determined by a random-effects model. Heterogeneity was explored using sensitivity analysis, subgroup analysis, and random effects meta-regression. Of 2314 references, 11 studies (47,179 participants) were included in the meta-analysis. The overall pooled prevalence of MCI in patients with hypertension was 30% (95% CI, 25-35), with significant heterogeneity present (I2 = 99.3%, p less then 0.001). In subgroup analyses, Asian and European samples had a prevalence of 26% (95% CI, 20-31) and 40% (95% CI, 14-66), respectively; cross-sectional and cohort studies had a prevalence of 28% (95% CI, 24-32) and 38% (95% CI, -5-81); age older than 60 years had a prevalence of 28% (95% CI, 23-33); community-based and clinic-based samples had a prevalence of 17% (95% CI, 15-19) and 42% (95% CI, 23-62); and MCI diagnosis using the MoCA, NIA-AA, MMSE, and Peterson criteria had a prevalence of 64% (95% CI, 59-68), 18% (95% CI, 16-19), 19% (95% CI, 15-23), and 13% (95% CI, 9-17). Meta-regression analysis showed that different MCI diagnostic criteria could be the source of heterogeneity in the pooled results. MCI is common in patients with hypertension, with an overall prevalence of 30%. Earlier cognitive screening and management in hypertensi