[Genetic analysis of a rare fetus with mandibulofacial dysostosis Guion-Almeida type].

OBJECTIVE: To delineate the clinical and genetic features of a fetus with micrognathia, low-set ears, microtia, polyhydramnios and anechoic stomach by ultrasonography. METHODS: Whole exome sequencing (WES) was carried out to detect genetic variant in the fetus, for which routine chromosomal karyotyping and chromosomal microarray analysis (CMA) yielded no positive finding. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: WES revealed that the fetus has carried a de novo nonsense c.2302C>T (p.Q768X) variant in exon 23 of the EFTUD2 gene, which was detected in neither parent. The variant was unreported previously and may lead to premature termination of the translation of EFTUD2 protein at the 768th amino acid. Bioinformatic analysis predicted the amino acid to be highly conserved and may alter the structure and function of the EFTUD2 protein. CONCLUSION: The c.2302C>T variant of the EFTUD2 gene probably underlay the mandibulofacial dysostosis Guion-Almeida type in the fetus. Discovery of the novel variant has enriched variant spectrum of the EFTUD2 gene and provided a basis for genetic counseling and prenatal diagnosis for the family.

Parameter estimation for chaotic systems using a hybrid adaptive cuckoo search with simulated annealing algorithm.

This paper introduces a novel hybrid optimization algorithm to establish the parameters of chaotic systems. In order to deal with the weaknesses of the traditional cuckoo search algorithm, the proposed adaptive cuckoo search with simulated annealing algorithm is presented, which incorporates the adaptive parameters adjusting operation and the simulated annealing operation in the cuckoo search algorithm. Normally, the parameters of the cuckoo search algorithm are kept constant that may result in decreasing the efficiency of the algorithm. For the purpose of balancing and enhancing the accuracy and convergence rate of the cuckoo search algorithm, the adaptive operation is presented to tune the parameters properly. Besides, the local search capability of cuckoo search algorithm is relatively weak that may decrease the quality of optimization. So the simulated annealing operation is merged into the cuckoo search algorithm to enhance the local search ability and improve the accuracy and reliability of the results. The functionality of the proposed hybrid algorithm is investigated through the Lorenz chaotic system under the noiseless and noise condition, respectively. The numerical results demonstrate that the method can estimate parameters efficiently and accurately in the noiseless and noise condition. Finally, the results are compared with the traditional cuckoo search algorithm, genetic algorithm, and particle swarm optimization algorithm. Simulation results demonstrate the effectiveness and superior performance of the proposed algorithm.

[Prenatal ultrasonic manifestation and clinical significance of fetal hemivertebra].

OBJECTIVE: To explore the manifestation and clinical significance of prenatal ultrasound diagnosis of fetal hemivertebra. METHODS: In the study, 27 fetals with hemivertebras (proven by post-natal X-ray, CT or MR) were examined by prenatal ultrasound and MR in Women & Children's Hospital, Ningbo, Zhejiang. Two-dimensional and three-dimensional prenatal ultrasonic manifestations were retrospective analyzed and compared with the prenatal MR diagnoses, the post-natal X-ray, CT, MR examinations. All the fetuses were carried out karyotype examinations. The full-term births recieved surgical treatment and the Cobb angle correction rate was calculated. RESULTS: The 27 cases of fetal ultrasound showed the morphological changes of the spine, with the involved segment only half of the vertebra, in which 9 cases were single hemivertebra and 18 cases multiple, 8 cases were no malformation and 19 cases other malformations, and 19 cases were induction of labor, and 8 cases of term delivery. Compared with postpartum X-ray and other imaging tests, the prenatal ultrasound accuracy rate was 92.5%, and prenatal MR 96.3%. In the 27 cases, the chromosome cultures of 25 cases were successful, in which the normal karyotype was 68.0% (17/25), and abnormal karyotype 32.0% (8/25) with multiple hemivertebra accounting for 47.1% (8/17). In 8 cases with posterior approach of hemivertebra resection, 6 patients were less than and equal to 3 years old, whose average Cobb angle correction rate was 38.02%, and 2 more than 3 years old, whose average Cobb angle correction rate was 24.98%. CONCLUSION: Fetal hemivertebra have typical sonographic manifestations. In diagnosis of fetal hemivertebra, the accuracy of prenatal ultrasound is close to that of MR, which has important clinical implications in diagnosis and overall assessment of fetal hemivertebra, and can also provide appropriate clinical genetic reference.

Application of whole exome sequencing in fetal cases with skeletal abnormalities.

Objectives: To investigate the role of whole exome sequencing (WES) technology in fetuses with skeletal abnormalities (SKA) for establishing an appropriate clinical diagnosis and treatment path. Methods: From April 2019 to August 2020, eight special families were enrolled into the study. Their fetuses showed abnormal SKA by ultrasonic testing during pregnancy, but it is inconsistent with the normal results identified by chromosomal microarray analysis (CMA) of amniotic fluid or abortion. For further diagnosis, WES was performed to detect the causative genes mutations followed by Sanger sequencing. Results: Among of these eight fetuses with SKA, we found more than half of pathogenic mutations were in COL1A1/2 gene, except for a known hotspot mutation in FGFR3 gene (c.1138G>A). Three heterozygous mutations of COL1A1 gene, c.2885G>A p (Gly962Asp), c.994G>A p (Gly332Arg) and c.1002 + 5G>T, were de novo mutations. The c.1002 + 5G>T mutation in COL1A1 was firstly reported. In addition, one fetus carried a novel heterozygous mutation of COL1A1 c.644G>A p (Gly215Asp), which was inherited from the mother. Another novel heterozygous mutation c.2482G>T p (Val828Phe) in the COL1A2 gene was identified in another fetus and was inherited from the father. Among of these COL1A1 mutations, these results might involve in two novel splicing mutations. Conclusion: Our study reported several novel heterozygous mutations which expands the COL1A1/2 mutation spectrum for prenatal diagnosis of SKA. Most importantly, WES technology is necessary as a routine step of the SKA diagnosis before or during pregnancy, combining with the detection of chromosome level.

An Improved Cuckoo Search Optimization Algorithm for the Problem of Chaotic Systems Parameter Estimation.

This paper proposes an improved cuckoo search (ICS) algorithm to establish the parameters of chaotic systems. In order to improve the optimization capability of the basic cuckoo search (CS) algorithm, the orthogonal design and simulated annealing operation are incorporated in the CS algorithm to enhance the exploitation search ability. Then the proposed algorithm is used to establish parameters of the Lorenz chaotic system and Chen chaotic system under the noiseless and noise condition, respectively. The numerical results demonstrate that the algorithm can estimate parameters with high accuracy and reliability. Finally, the results are compared with the CS algorithm, genetic algorithm, and particle swarm optimization algorithm, and the compared results demonstrate the method is energy-efficient and superior.

Forecasting nonlinear chaotic time series with function expression method based on an improved genetic-simulated annealing algorithm.

The paper proposes a novel function expression method to forecast chaotic time series, using an improved genetic-simulated annealing (IGSA) algorithm to establish the optimum function expression that describes the behavior of time series. In order to deal with the weakness associated with the genetic algorithm, the proposed algorithm incorporates the simulated annealing operation which has the strong local search ability into the genetic algorithm to enhance the performance of optimization; besides, the fitness function and genetic operators are also improved. Finally, the method is applied to the chaotic time series of Quadratic and Rossler maps for validation. The effect of noise in the chaotic time series is also studied numerically. The numerical results verify that the method can forecast chaotic time series with high precision and effectiveness, and the forecasting precision with certain noise is also satisfactory. It can be concluded that the IGSA algorithm is energy-efficient and superior.