Bi-allelic loss-of-function variants in TMEM147 cause moderate to profound intellectual disability with facial dysmorphism and pseudo-Pelger-Huët anomaly.

The transmembrane protein TMEM147 has a dual function: first at the nuclear envelope, where it anchors lamin B receptor (LBR) to the inner membrane, and second at the endoplasmic reticulum (ER), where it facilitates the translation of nascent polypeptides within the ribosome-bound TMCO1 translocon complex. Through international data sharing, we identified 23 individuals from 15 unrelated families with bi-allelic TMEM147 loss-of-function variants, including splice-site, nonsense, frameshift, and missense variants. These affected children displayed congruent clinical features including coarse facies, developmental delay, intellectual disability, and behavioral problems.

Feasibility and efficacy of sepsis management guidelines in a pediatric intensive care unit in Saudi Arabia: a quality improvement initiative.

Objectives: Evaluation of feasibility and effectiveness of Surviving Sepsis Campaign (SSC) Guidelines implementation at a Pediatric Intensive Care Unit (PICU) in Saudi Arabia to reduce severe sepsis associated mortality.

Design: Retrospective data analysis for a prospective quality improvement (QI) initiative.

Settings: PICU at King Saud University Medical City, Saudi Arabia.

Effect of second order signal-noise interactions in nonlinearity compensated optical transmission systems.

In this Letter, we theoretically and numerically analyze the performance of coherent optical transmission systems that deploy inline or transceiver based nonlinearity compensation techniques. For systems where signal-signal nonlinear interactions are fully compensated, we find that beyond the performance peak the signal-to-noise ratio degradation has a slope of 3 dBSNR/dBPower suggesting a quartic rather than quadratic dependence on signal power. This is directly related to the fact that signals in a given span will interact not only with linear amplified spontaneous emission noise, but also with the nonlinear four-wave mixing products generated from signal-noise interaction in previous (hitherto) uncompensated spans.

Prevalence of thrombophilic genetic factors among patients with retinitis pigmentosa.

Purpose: To determine the prevalence of thrombophilic factors in patients with retinitis pigmentosa (RP).

Methods: Fifty consecutive patients with RP and 50 controls matched by age and gender were tested for the presence of the following mutations: factor II (GA20210), factor V Leiden (GA1691), methylenetetrahydrofolate reductase (CT677), factor XIIIa (Val→Leu), β-fibrinogen (GA455), tumor necrosis factor receptor (TNFRII) (M196R), plasminogen activator inhibitor-1 (PAI-1) (4 G/5 G), and plasminogen activator inhibitor-1 (PAI-1) (GA844).

Results: The following heterozygous mutations were found in patients/controls: factor V Leiden (12/14), factor XIIIa (20/30), methylenetetrahydrofolate reductase 677 TT (48/52), β-fibrinogen GA455 (36/36), TNFRII (M196R) (40/42), PAI-1 4 G/5 G (40/48), and PAI-1 GA844 (50/52).