Upper limb muscle overgrowth with hypoplasia of the index finger: a new over-growth syndrome caused by the somatic PIK3CA mutation c.3140A>G.

BACKGROUND: Scientists have previously described an overgrowth syndrome in Saudi patients and named it 'Upper limb muscle overgrowth with hypoplasia of the index finger' syndrome. CASE PRESENTATION: We describe a new case and document that the syndrome is caused by the somatic PIK3CA mutation c.3140A>G, p.His1047Arg. We also recruited one of the previously reported cases and found the same somatic mutation in the affected muscles. A wider classification of 'PIK3CA-related pathology spectrum' is presented which includes cancer, benign skin lesions/tumors, Cowden syndrome, isolated vascular malformations and various overgrowth syndromes. The latter entity is sub-divided into 3 sub-groups: overgrowth with brain involvement, overgrowth with multiple lipomatosis, and overgrowth without brain involvement/multiple lipomatosis. CONCLUSION: Our literature review indicated that "upper limb muscle overgrowth with hypoplasia of the index finger" is not as rare as previously thought to be. This overgrowth syndrome is unique and is caused by the somatic PIK3CA mutation c.3140A>G.

Silver nanoparticles inhibit the gill Na⁺/K⁺-ATPase and erythrocyte AChE activities and induce the stress response in adult zebrafish (Danio rerio).

Silver nanoparticles (AgNPs) are the most commonly used metallic nanoparticles in industrial applications, including medical and consumer products. In the recent years, however, concerns regarding their environmental and health impacts have emerged. Aquatic organisms are of special concern since water bodies often serve as sinks for anthropogenic activities. This study assessed the effects of AgNPs on the activities of the gill Na(+)/K(+)-ATPase and erythrocyte acetylcholinestrase (AChE), as well as the plasma biochemistry in adult zebrafish (Danio rerio). In an acute exposure scenario the fish were exposed for 4d to 16.76 mg/L AgNPs, which was the 96 h LC50 value determined in preliminary experiments. In a prolonged exposure scenario the fish were exposed for 1, 2, or 3 weeks to AgNPs at concentrations of 2 and 4 mg/L, corresponding to the 1/10th and 2/10th of the 96 h LC50 value. Generally the activity of the gill Na(+)/K(+)-ATPase decreased, but this was only significant starting at 14 d of the prolonged exposure scenario, whereas the activity of the erythrocyte AChE was significantly decreased in both exposure scenarios. Finally, the plasma electrolytes levels were reduced and the plasma glucose and cortisol levels were increased in exposed fish. This study demonstrates that AgNPs could inhibit the activities of Na(+)/K(+)-ATPase and AChE, thus interfering with the proper ionoregulation and neuroregulation, respectively, and act as stressors.

A classification system for split-hand/ foot malformation (SHFM): A proposal based on 3 pedigrees with WNT10B mutations.

SHFM6 (OMIM 225300) is caused by WNT10B pathogenic variants (12q13.12). It is one of the rarest forms of SHFM; with only seven pathogenic variants described in the world literature. Furthermore, it has not been determined if SHFM6 has specific phenotypic characteristics. In this paper, we present a case series of three unrelated families with SHFM6 caused by three novel WNT10B pathogenic variants. The index patient of the first family was homozygous for the nonsense variant c.676C > T (p.Arg226*) in the WNT10B gene. The index case of the second family had a homozygous splice variant c.338-1G > C in the WNT10B gene. Finally, the index case of the third family carried two different variants in the WNT10B gene: A nonsense variant (p.Arg226*), and a missense variant (p.Gln86Pro). The latter represents the first compound heterozygous pathogenic variant related to SHFM6. We also offer a classification system for the hand/foot defects to illustrate the specific phenotypic characteristics of SHFM6. Based on this classification and a review of all previously reported cases, we demonstrate that SHFM6 caused by WNT10B pathogenic variants have the following characteristics: more severe feet defects (compared to the hand defects), polydactyly, severe flexion digital contractures, and phalangeal dysplasia.

Effects of protocol-based management on the post-operative outcome after systemic to pulmonary shunt.

OBJECTIVES: Systemic to pulmonary shunt (commonly known as Modified Blalock-Taussig shunt) is a palliative procedure in cyanotic heart diseases to overcome inadequate blood flow to the lungs. Based on the most recent risk stratification score, the mortality and morbidity of this procedure is still high especially in neonates and over-shunting patients. We developed and implemented protocol-based management in March 2013 to better standardize the management of these patients. The aim of this study is to evaluate the effects of applying this protocol-based management in our center. METHODS: We conducted a retrospective cohort study through chart review analysis.We included all children who underwent MBTS from January 2000 till December 2015. We compared the early postoperative outcome of patients operated after the protocol-based management implementation (March 2013 till December 2015) (protocol group) with patients operated before implementing the MBTS protocoled management (control group). RESULTS: 197 patients underwent MBTS from January 2000 till December 2015. Of the 197 patients, 25 patients were in the protocol group and 172 patients were in the control group. There was a significant improvement in the postoperative course and less morbidity after protocoled management implementation as reflected in ventilation time, reintubation rate, inotropic support duration, intensive care unit ICU stay and significantly lower postoperative complications in the protocol group. Mortality of the control group versus protocol group (19.3% VS 8%) with Standardized Mortality Ratio (SMR) dropped from 2.27 before protocoled management to 0.94 after protocoled management (protocol group). CONCLUSION: The study suggests that protocoled management of patients with MBTS can improve the postoperative course and early outcome.

Analysis of CCR5 gene polymorphisms in 321 healthy Saudis using Next Generation Sequencing.

AIMS: To investigate the extent of CCR5 polymorphism in the healthy Saudi population. METHOD: A total of 321 healthy Saudi individuals were sequenced using the ion Ampliseq™ Exome kit (Life Technologies, USA) on genomic DNA following manufacturer's protocol. Whole Exome Sequencing (WES) reads were aligned to the human reference genome (hg19 build) with Torrent Suite Software (v5.0.2) and the variants were called using the Torrent Variant Caller plugin (v5.0) and imported into Ion Reporter Server (v5.0) for the annotation. CCR5 coding exons variants were filtered and checked against the NHLBI GO Exome Sequencing Project (NHLBI), NCBI Reference dbSNPs database, 1000 genomes and Exome Aggregation Consortium datasets (ExAC). RESULTS: A total of 475 variants were identified. Table 1 shows polymorphisms/mutations detected within exons that introduced an amino acid change, deletion or copy number variants (CNV). Three mutations are predicted to influence CCR5 function, including the 32bp deletion (Rs333). Four polymorphisms were detected, plus two CNV. CONCLUSIONS: This is the first report on sequencing the full CCR5 gene using NGS in the Saudi population. Here we demonstrate seven polymorphisms/mutations that were reported before. All were detected within very low frequency including the delta 32 mutation. However, we report for the first time copy number variants at two CCR5 gene locations; 45072265 and 38591712.