[Analysis of clinical features and genetic variant in a child with Cowden syndrome 1].

OBJECTIVE: To explore the genetic etiology of a child with Cowden syndrome 1 (CS1). METHODS: A child who had visited the Ningbo Women and Children's Hospital on August 26, 2022 was selected as the study subject. Clinical information of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his family members and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RESULTS: The child, a 13-year-old boy, had manifested with severe mental retardation, hyperactivity, autistic behavior, sparse and prominent teeth, macrocephaly, and skin freckles on the penis. His mother had presented with multiple papules, hamartomatous polyps, thyroid adenoma and macrocephaly. WES results revealed that the child has harbored a nonsense c.781C>T (p.Q261*) variant of the PTEN gene, which was inherited from his mother. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.781C>T variant was classified as likely pathogenic (PVS1+PM2_Supporting). CONCLUSION: The c.781C>T variant of the PTEN gene probably underlay the pathogenesis in the child and his mother. Above finding has facilitated genetic counseling for this family.

Prenatal diagnosis to identify compound heterozygous variants in PKDCC that causes rhizomelic limb shortening with dysmorphic features in a fetus from China.

BACKGROUND: Rhizomelic limb shortening with dysmorphic features (RLSDF) has already been a disorder of the rare autosomal recessive skeletal dysplasia, just having a few reported cases. RLSDF is caused by protein kinase domain containing, cytoplasmic(PKDCC)gene variants. In this study, we describe the clinical features and potential RLSDF molecular etiology in a fetus from China. METHODS: Genomic DNA (gDNA) extracted from the fetal muscle tissue and parents' peripheral blood was subjected to chromosomal microarray analysis (CMA) and trio-based whole exome sequencing (Trio-WES). The candidate pathogenic variants were verified by using Sanger sequencing. RESULTS: Trio-WES identified two compound heterozygous variants in PKDCC, c.346delC (p.Pro117Argfs*113) and c.994G > T (p.Glu332Ter), inherited from the father and mother, respectively. Both variants are classified as pathogenic according to American College of Medical Genetics and Genomics guidelines. CONCLUSIONS: We reported the first prenatal case of RLSDF caused by PKDCC in the Chinese population. Our findings extended the variation spectrum of PKDCC and emphasized the necessity of WES for the early diagnosis of skeletal dysplasia and other ultrasound structural abnormalities in fetuses.

[Clinical characteristics and genetic analysis of a fetus with Melnick-Needles syndrome due to variant of FLNA gene].

OBJECTIVE: To explore the clinical and genetic characteristics of a fetus with Melnick-Needles syndrome (MNS). METHODS: A fetus with MNS diagnosed at Ningbo Women and Children's Hospital in November 2020 was selected as the study subject. Clinical data was collected. Pathogenic variant was screened by using trio-whole exome sequencing (trio-WES). Candidate variant was verified by Sanger sequencing. RESULTS: Prenatal ultrasonography of the fetus had shown multiple anomalies including intrauterine growth retardation, bilateral femur curvature, omphalocele, single umbilical artery, and oligohydramnios. Trio-WES revealed that the fetus has harbored hemizygous c.3562G>A (p.A1188T) missense variant of the FLNA gene. Sanger sequencing confirmed that the variant was maternally derived, whilst its father was of a wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS4+PM2_Supporting+PP3+PP4). CONCLUSION: The hemizygous c.3562G>A (p.A1188T) variant of the FLNA gene probably underlay the structural abnormalities in this fetus. Genetic testing can facilitate accurate diagnosis of MNS and provide a basis for genetic counseling for this family.

The role of 25(OH)D3 and circRNAs in early diagnosis of gestational diabetes mellitus.

OBJECTIVE: To explore the relationship between 25(OH)D3 and circular RNAs (circRNAs) in the early diagnosis of gestational diabetes mellitus (GDM) and to screen for biological markers for early prediction of GDM. METHODS: A cohort study was conducted using samples and data collected from pregnant women registered at the Li Huili hospital in China between April 2018 and January 2020. Four circRNAs (hsa_circ_0003218, hsa_circ_0002968, hsa_circ_0007430, and hsa_circ_0006260) were selected as potential biomarkers, and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to measure their concentration in the serum and to analyze their correlation with 25(OH)D3. The Pearson correlation test was used to assess the correlation between the 25(OH)D3, circRNAs, and various clinical variables. The area under the receiver operating characteristic (ROC) curve was used to assess the diagnostic value of circRNAs and 25(OH)D3 in the early stage of pregnancy. RESULTS: Weight, body mass index (BMI), triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and 25(OH)D3 were found to be risk factors for GDM. The level of 25(OH)D3 correlated significantly with HDL-C with a correlation coefficient of 0.298 (p < 0.05). The expression of hsa_circ_0003218 was significantly downregulated in the GDM group (p < 0.05). Hsa_circ_0002968, hsa_circ_0007430, and hsa_circ_0006260 did not show any differential expression between the two groups (p > 0.05). Furthermore, hsa_circ_0003218 level correlated significantly with 25(OH)D3 and the correlation coefficient was 0.357 (p < 0.05). The AUC of hsa_circ_0003218 combined with 25(OH)D3 was 0.789 ([0.700-0.877], p < 0.001), with sensitivity and specificity of 63.04% and 80.65%, respectively. CONCLUSIONS: Hsa_circ_0003218 and 25(OH)D3 may jointly participate in the metabolic process of GDM. Thus, the combination of 25(OH)D3 and hsa_circ_0003218 represents a potential biomarker for the prediction of GDM in the early stages of pregnancy.

Two-dimensional grating coupler with a low polarization dependent loss of 0.25 dB covering the C-band.

We design and demonstrate a two-dimensional grating coupler (2D GC) with a low polarization dependent loss (PDL) based on the silicon-on-insulator (SOI) platform. Using a grating cell consisting of five cylinders and carefully optimizing the distances between the cylinders, a maximum PDL of 0.25 dB covering the C-band is realized, which is 1.25 dB better than a conventional 2D GC with a single cylinder etching pattern fabricated on the same SOI wafer.

Single step etched two dimensional grating coupler based on the SOI platform.

We design and demonstrate a single step etched two dimensional grating coupler (2D GC) based on the silicon-on-insulator (SOI) platform using subwavelength cylinders. Taking the lag effect into consideration, the 2D GC is manufactured in the same lithography and etching processes with the strip waveguide. The measured coupling loss of the proposed 2D GC is -6.0 dB, which is comparable with conventional shallowly etched 2D GC, realizing a fabrication simplification without performance degradation.

Ultra efficient silicon nitride grating coupler with bottom grating reflector.

We theoretically propose a silicon nitride (Si(3)N(4)) grating coupler (GC) with both ultrahigh efficiency and simplified fabrication processes. Instead of using a bottom distributed Bragg reflector (DBR) or metal reflector, a bottom Si grating reflector (GR) with comparable reflectivity is utilized to improve the coupling efficiency. The fully etched Si GR is designed based on an industrially standard silicon-on-insulator (SOI) wafer with 220 nm top Si layer. By properly adjusting the trench width and period length of the Si GR, a high reflectivity over 90% is obtained. The Si(3)N(4) GC is optimized based on a common 400 nm Si(3)N(4) layer sitting on the Si GR with a SiO(2) separation layer. With an appropriate distance between the Si(3)N(4) GC and bottom Si GR, a low coupling loss of -1.47 dB is theoretically obtained using uniform GC structure. A further record ultralow loss of -0.88 dB is predicted by apodizing the Si(3)N(4) GC. The specific fabrication processes and tolerance are also investigated. Compared with DBR, the bottom Si GR can be easily fabricated by single step of patterning and etching, simplifying the fabrication processes.

Short and efficient mode-size converter designed by segmented-stepwise method.

We present an efficient segmented-stepwise method to design a short and low-loss mode-size converter. A silicon-on-insulator platform-based converter with 20 µm length and 95.2% conversion efficiency is acquired by taking only 10 optimization generations using 2D-FDTD method. A 3D-FDTD simulation is performed to verify the calculated results, returning an efficiency of 92.1%. The proposed device can be used to connect a 12-µm-wide waveguide and a 0.5-µm-wide single-mode waveguide, with comparable performance of a regular scheme using 150-µm-long linear taper. For demonstration, the converter was fabricated by electron-beam-lithography and inductively-coupled-plasma etching. A conversion loss of -0.62±0.02 dB at 1550 nm was experimentally measured.

An SOI based polarization insensitive filter for all-optical clock recovery.

We fabricate and demonstrate a compact polarization insensitive filter for all-optical clock recovery (CR) based on silicon-on-insulator (SOI), which consists of a microring resonator (MRR) and two modified two-dimensional (2D) grating couplers. The distributed Bragg reflectors (DBRs) are introduced to improve the coupling efficiency of the 2D grating coupler. The MRR works as a comb filter for CR, while the 2D grating couplers serve as the polarization diversity unit to achieve a polarization insensitive operation. A subsequent semiconductor optical amplifier (SOA) performs the amplitude equalization. Based on this scheme, a good clock signal with 970 fs timing jitter can be achieved at 44 Gb/s from input signals with arbitrary polarization states.

On-chip multiplexing conversion between wavelength division multiplexing-polarization division multiplexing and wavelength division multiplexing-mode division multiplexing.

A compact silicon-on-insulator device used for conversions between polarization division multiplexing (PDM) and mode division multiplexing (MDM) signals is proposed and experimentally demonstrated by utilizing a structure combining the improved two-dimensional grating coupler and two-mode multiplexer. The detailed design of the proposed device is presented and the results show the extinction ratio of 16 and 20 dB for X- and Y-pol input, respectively. The processing of 40 Gb/s signal is achieved within the C-band with good performance. The proposed converter is capable of handling multiple wavelengths in wavelength division multiplexing (WDM) networks, enabling the conversions between WDM-PDM and WDM-MDM, which is promising to further increase the throughput at the network interface.

Silicon based polarization insensitive filter for WDM-PDM signal processing.

We propose and fabricate a novel circuit that combines two two-dimensional (2D) grating couplers and a microring resonator (MRR). According to the polarization states, one 2D grating coupler first splits the input signals into two orthogonal paths, which co-propagate in the loop and share a common MRR, and then the two paths are combined together by the other 2D grating coupler. The proposed circuit is polarization insensitive and can be used as a polarization insensitive filter. For demonstration, the wavelength division and polarization division multiplexing (WDM-PDM) non return-to-zero differential-phase-shift-keying (NRZ-DPSK) signals can be demodulated successfully. The bit error ratio measurements show an error free operation, reflecting the good performance and the practicability.

High-order all-optical differential equation solver based on microring resonators.

We propose and experimentally demonstrate a feasible integrated scheme to solve all-optical differential equations using microring resonators (MRRs) that is capable of solving first- and second-order linear ordinary differential equations with different constant coefficients. Employing two cascaded MRRs with different radii, an excellent agreement between the numerical simulation and the experimental results is obtained. Due to the inherent merits of silicon-based devices for all-optical computing, such as low power consumption, small size, and high speed, this finding may motivate the development of integrated optical signal processors and further extend optical computing technologies.

SOI based ultracompact polarization insensitive filter for PDM signal processing.

We propose and fabricate a scheme that combines a two-dimensional (2D) grating coupler and a delay interferometer (DI) in a loop configuration. According to the polarization states, the 2D grating coupler first splits the input signals into two paths, which copropagate in the loop and share a common DI, and then combines the two paths together to the same input port. The proposed device is polarization insensitive and can be used for polarization division multiplexed (PDM) signal processing. For demonstration, the PDM non return-to-zero differential-phase-shift-keying signals can be demodulated successfully. The bit error ratio measurements show an error free operation, reflecting the good performance and the practicability of the proposed device.