Atrial fibrillation (AF) is a common cardiac arrhythmia whose molecular etiology is poorly understood. We studied a family with hereditary persistent AF and identified the causative mutation (S140G) in the KCNQ1 (KvLQT1) gene on chromosome 11p15.5. The KCNQ1 gene encodes the pore-forming alpha subunit of the cardiac I(Ks) channel (KCNQ1/KCNE1), the KCNQ1/KCNE2 and the KCNQ1/KCNE3 potassium channels. Functional analysis of the S140G mutant revealed a gain-of-function effect on the KCNQ1/KCNE1 and the KCNQ1/KCNE2 currents, which contrasts with the dominant negative or loss-of-function effects of the KCNQ1 mutations previously identified in patients with long QT syndrome. Thus, the S140G mutation is likely to initiate and maintain AF by reducing action potential duration and effective refractory period in atrial myocytes.

Objective: We used data from twins and their families to probe the genetic factors contributing to microtia-atresia, in particular, early post-twinning variations that potentially account for the discordant phenotypes of monozygotic twin pairs. Methods: Six families of monozygotic twins discordant for congenital microtia-atresia were recruited for study. The six patients shared a consistent clinical phenotype of unilateral microtia-atresia. Whole-exome sequencing (WES) was performed for all six twin pairs and their parents. Family segregation and multiple bioinformatics methods were applied to identify suspicious mutations in all families. Recurring mutations commonly detected in at least two families were highlighted. All variants were validated via Sanger sequencing. Gene Ontology (GO) analysis was performed to identify candidate gene sets and related pathways. Copy number variation (CNV), linkage analysis, association analysis and machine learning methods were additionally applied to isolate candidate mutations, and comparative genomics and structural modeling tools used to evaluate their potential roles in onset of microtia-atresia. Results: Our analyses revealed 61 genes with suspected mutations associated with microtia-atresia. Five (HOXA4, MUC6, CHST15, TBX10, and AMER1) contained 7 de novo mutations that appeared in at least two families, which have been previously reported as pathogenic for other diseases. Among these, HOXA4 (c.920A>C, p.H307P) was determined as the most likely pathogenic variant for microtia-atresia. GO analysis revealed four gene sets involving 11 pathways potentially related to underlying pathogenesis of the disease. CNVs in three genes (UGT2B17, OVOS, and KATNAL2) were detected in at least two families. Linkage analysis disclosed 13 extra markers for the disease, of which two (FGFR1 and EYA1) were validated via machine learning analysis as plausible candidate genes for the disease.

Untethered submillimeter microrobots have significant application prospects in environment monitoring, reconnaissance, and biomedicine. However, they are practically limited to their slow movement. Here, an electrical/opticalactuated microactuator is reported and developed into several untethered ultrafast submillimeter robots. Composed of multilayer nanofilms with exquisitely designed patterns and high surface-to-volume ratios, the microrobot exhibits flexible, precise, and rapid response under voltages and lasers, resulting in controllable and ultrafast inchworm-type movement. The proposed design and microfabrication approach allows various improved and distinctive 3D microrobots simultaneously. The motion speed is highly related to the laser frequency and reaches 2.96 mm/s (3.66 body length/s) on the polished wafer surface. Excellent movement adaptability of the robot is also verified on other rough substrates. Moreover, directional locomotion can be realized simply by the bias of the irradiation of the laser spot, and the maximum angular speed reaches 167.3°/s. Benefiting from the bimorph film structure and symmetrical configuration, the microrobot is able to maintain functionalized after being crashed by a payload 67 000 times heavier than its weight, or at the unexpectedly reversed state. These results provide a strategy for 3D microactuators with precise and rapid response, and microrobots with fast movement for delicate tasks in narrow and restrictive scenarios.

Waardenburg syndrome type 2 (WS2) is a rare genetic disorder, characterized by bright blue eyes, moderate to profound hearing loss and pigmental abnormalities of the hair and skin. Between 10 and 20 mutations in the SRY-box 10 (SOX10) gene were previously identified to be associated with WS2. The present study aimed to identify the genetic causes of WS2 in a Chinese family. Clinical and molecular analyses were performed to genetically characterize a Chinese family with two cases of WS2. The clinical data of the proband were collected using a questionnaire. The genomic DNA was extracted from peripheral blood samples of each individual in the family, and 168 candidate genes associated with hearing loss were sequenced using the Illumina HiSeq 2000 and confirmed by Sanger sequencing. A heterozygous nonsense mutation [substitution; position 127; cytosine to thymine (c.127C>T)] was identified in exon 2 of SOX10 (transcript ID: NM_006941.3) in the proband and the mother; however, not in other family members or healthy controls. The novel nonsense heterozygous mutation may cause the replacement of codon 43 [arginine (Arg)] with a stop codon (Arg43stop), leading to premature termination of protein translation. The novel nonsense heterozygous mutation c.127C>T in the SOX10 gene was considered to be the cause of WS2 in the family. This mutation has not been identified in any databases, to the best of the authors' knowledge, including The Single Nucleotide Polymorphism Database, The Human Gene Mutation Database, 1000 Genomes Project and ClinVar and Exome Sequencing Project v. 6500.

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