Hyperbolic-to-hyperbolic transition at exceptional Reststrahlen point in rare-earth oxyorthosilicates.

Anisotropic optical crystals can exhibit a hyperbolic response within the Reststrahlen band (RB) and support directional polaritonic propagations when interacting with light. Most of the reported low-symmetry optical crystals showcase the evolution from hyperbolic to elliptic dispersion topologies, largely owing to their adjacent RBs being either overlapped or separated. Here, we report an exceptional Reststrahlen point (ERP) in rare-earth oxyorthosilicate Y2SiO5, at which two neighboring RBs almost kiss each other. Consequently, we observe the direct hyperbolic-to-hyperbolic topological transition: the hyperbolic branches close and reopen along with the rotating transverse axis (TA). At such ERP, the TA merges to the direction orthogonal to its proximate phonon mode, mainly due to the interplay between these two non-orthogonal phonon modes. We also find that even with the existence of only one single RB, the TA can rotate in-plane. Our findings are prevalent in isostructural rare-earth oxyorthosilicates, such as Lu2SiO5. The universally underlying physics of ERP and its corresponding special class of rare-earth oxyorthosilicates may offer playgrounds for continuously tuning phonon polariton propagation direction, and broadband controlling light dispersion of polaritonic nanodevices.

Patterns of Cytogenomic Findings from a Case Series of Recurrent Pregnancy Loss Provide Insight into the Extent of Genetic Defects Causing Miscarriages.

Background A retrospective study was performed to evaluate the patterns of cytogenomic findings detected from a case series of products of conception (POC) in recurrent pregnancy loss (RPL) over a 16-year period from 2007 to 2023. Results This case series of RPL was divided into a single analysis (SA) group of 266 women and a consecutive analysis (CA) group of 225 women with two to three miscarriages analyzed. Of the 269 POC from the SA group and the 469 POC from the CA group, a spectrum of cytogenomic abnormalities of simple aneuploidies, compound aneuploidies, polyploidies, and structural rearrangements/pathogenic copy number variants (pCNVs) were detected in 109 (41%) and 160 cases (34%), five (2%) and 11 cases (2%), 35 (13%) and 36 cases (8%), and 10 (4%) and 19 cases (4%), respectively. Patterns with recurrent normal karyotypes, alternating normal and abnormal karyotypes, and recurrent abnormal karyotypes were detected in 74 (33%), 71 (32%), and 80 (35%) of consecutive miscarriages, respectively. Repeat aneuploidies of monosomy X and trisomy 16, triploidy, and tetraploidy were detected in nine women. Conclusions A comparable spectrum of cytogenomic abnormalities was noted in the SA and CA groups of RPL. A skewed likelihood of 2/3 for recurrent normal and abnormal karyotypes and 1/3 for alternating normal and abnormal karyotypes in consecutive miscarriages was observed. Routine cytogenetic analysis should be performed for consecutive miscarriages. Further genomic sequencing to search for detrimental and embryonic lethal variants causing miscarriages and pathogenic variants inducing aneuploidies and polyploidies should be considered for RPL with recurrent normal and abnormal karyotypes.

Hybrid Ghost Phonon Polaritons in Thin-Film Heterostructure.

Ghost phonon polaritons (g-PhPs), a unique class of phonon polaritons in the infrared, feature ultralong diffractionless propagation (>20 µm) across the surface and tilted wavefronts in the bulk. Here, we study hybrid g-PhPs in a heterostructure of calcite and an ultrathin film of the phase change material (PCM) In3SbTe2, where the optical field is bound in the PCM film with enhanced confinement compared with conventional g-PhPs. Near-field optical images for hybrid g-PhPs reveal a lemniscate pattern in the momentum distribution. We fabricated In3SbTe2 gratings and investigated how different orientations and periodicities of gratings impact the propagation of hybrid g-PhPs. As the grating period decreases to zero, the wavefront of hybrid g-PhPs can be dynamically steered by varying the grating orientation. Our results highlight the promise of hybrid g-PhPs with tunable functionalities for nanophotonic studies.

Spatiotemporal beating and vortices of van der Waals hyperbolic polaritons.

In conventional thin materials, the diffraction limit of light constrains the number of waveguide modes that can exist at a given frequency. However, layered van der Waals (vdW) materials, such as hexagonal boron nitride (hBN), can surpass this limitation due to their dielectric anisotropy, exhibiting positive permittivity along one optic axis and negativity along the other. This enables the propagation of hyperbolic rays within the material bulk and an unlimited number of subdiffractional modes characterized by hyperbolic dispersion. By employing time-domain near-field interferometry to analyze ultrafast hyperbolic ray pulses in thin hBN, we showed that their zigzag reflection trajectories bound within the hBN layer create an illusion of backward-moving and leaping behavior of pulse fringes. These rays result from the coherent beating of hyperbolic waveguide modes but could be mistakenly interpreted as negative group velocities and backward energy flow. Moreover, the zigzag reflections produce nanoscale (60 nm) and ultrafast (40 fs) spatiotemporal optical vortices along the trajectory, presenting opportunities to chiral spatiotemporal control of light-matter interactions. Supported by experimental evidence, our simulations highlight the potential of hyperbolic ray reflections for molecular vibrational absorption nanospectroscopy. The results pave the way for miniaturized, on-chip optical spectrometers, and ultrafast optical manipulation.

Van der Waals quaternary oxides for tunable low-loss anisotropic polaritonics.

The discovery of ultraconfined polaritons with extreme anisotropy in a number of van der Waals (vdW) materials has unlocked new prospects for nanophotonic and optoelectronic applications. However, the range of suitable materials for specific applications remains limited. Here we introduce tellurite molybdenum quaternary oxides-which possess non-centrosymmetric crystal structures and extraordinary nonlinear optical properties-as a highly promising vdW family of materials for tunable low-loss anisotropic polaritonics. By employing chemical flux growth and exfoliation techniques, we successfully fabricate high-quality vdW layers of various compounds, including MgTeMoO6, ZnTeMoO6, MnTeMoO6 and CdTeMoO6. We show that these quaternary vdW oxides possess two distinct types of in-plane anisotropic polaritons: slab-confined and edge-confined modes. By leveraging metal cation substitutions, we establish a systematic strategy to finely tune the in-plane polariton propagation, resulting in the selective emergence of circular, elliptical or hyperbolic polariton dispersion, accompanied by ultraslow group velocities (0.0003c) and long lifetimes (5 ps). Moreover, Reststrahlen bands of these quaternary oxides naturally overlap that of α-MoO3, providing opportunities for integration. As an example, we demonstrate that combining α-MoO3 (an in-plane hyperbolic material) with CdTeMoO6 (an in-plane isotropic material) in a heterostructure facilitates collimated, diffractionless polariton propagation. Quaternary oxides expand the family of anisotropic vdW polaritons considerably, and with it, the range of nanophotonics applications that can be envisioned.

Optical nanoimaging of laser-switched phase-change plasmonic infrared antennas.

We investigate the plasmonic properties of laser-printed chalcogenide phase-change material In3SeTb2 (IST) antennas through near-field nanoimaging. Antennas of varying lengths were fabricated by laser switching an amorphous IST film into its crystalline metallic state. Near-field imaging elucidates the pronounced field confinement and enhancement at the antenna extremities along with the emergence of different ordered plasmonic modes with increasing length. Compared to gold antennas, the PCM antennas exhibit slightly lower but still substantial near-field enhancement with greater compactness. The interplay between antenna length, illumination angle, and excitation frequency enables versatile control over the resonant near-field distribution. Our work provides deeper understanding and tunable functionalities of laser-printed PCM nanoantennas for potential applications in compact, dynamically reconfigurable nanophotonic devices.

Visible to mid-infrared giant in-plane optical anisotropy in ternary van der Waals crystals.

Birefringence is at the heart of photonic applications. Layered van der Waals materials inherently support considerable out-of-plane birefringence. However, funnelling light into their small nanoscale area parallel to its out-of-plane optical axis remains challenging. Thus far, the lack of large in-plane birefringence has been a major roadblock hindering their applications. Here, we introduce the presence of broadband, low-loss, giant birefringence in a biaxial van der Waals materials Ta2NiS5, spanning an ultrawide-band from visible to mid-infrared wavelengths of 0.3-16 µm. The in-plane birefringence Δn ≈ 2 and 0.5 in the visible and mid-infrared ranges is one of the highest among van der Waals materials known to date. Meanwhile, the real-space propagating waveguide modes in Ta2NiS5 show strong in-plane anisotropy with a long propagation length (>20 µm) in the mid-infrared range. Our work may promote next-generation broadband and ultracompact integrated photonics based on van der Waals materials.

Optical nanoimaging of highly-confined phonon polaritons in atomically-thin nanoribbons of α-MoO3.

Phonon polaritons (PhPs), collective modes hybridizing photons with lattice vibrations in polar insulators, enable nanoscale control of light. In recent years, the exploration of in-plane anisotropic PhPs has yielded new levels of confinement and directional manipulation of nano-light. However, the investigation of in-plane anisotropic PhPs at the atomic layer limit is still elusive. Here, we report the optical nanoimaging of highly-confined phonon polaritons in atomically-thin nanoribbons of α-MoO3 (5 atomic layers). We show that narrow α-MoO3 nanoribbons as thin as a few atomic layers can support anisotropic PhPs modes with a high confinement ratio (∼133 times smaller wavelength than that of light). The anisotropic PhPs interference fringe patterns in atomic layers are tunable depending on the PhP wavelength via changing the illumination frequency. Moreover, spatial control over the PhPs interference patterns is also achieved by varying the nanostructures' shape or nanoribbon width of atomically-thin α-MoO3. Our work may serve as an empirical reference point for other anisotropic PhPs that approach the thickness limit and pave the way for applications such as atomically integrated nano-photonics and sensing.

Ultrafast anisotropic dynamics of hyperbolic nanolight pulse propagation.

Polariton pulses-transient light-matter hybrid excitations-traveling through anisotropic media can lead to unusual optical phenomena in space and time. However, studying these pulses presents challenges with their anisotropic, ultrafast, and nanoscale field variations. Here, we demonstrate the creation, observation, and control of polariton pulses, with in-plane hyperbolic dispersion, on anisotropic crystal surfaces by using a time-resolved nanoimaging technique and our developed high-dimensional data processing. We capture and analyze movies of distinctive pulse spatiotemporal dynamics, including curved ultraslow energy flow trajectories, anisotropic dissipation, and dynamical misalignment between phase and group velocities. Our approach enables analysis of polariton pulses in the wave vector time domain, demonstrating a time-domain polaritonic topological transition from lenticular to hyperbolic dispersion contours and the ability to study the polariton-induced time-varying optical forces. Our findings promise to facilitate the study of diverse space-time phenomena at extreme scales and drive advances in ultrafast nanoimaging.

Integrated exome sequencing and microarray analyses detected genetic defects and underlying pathways of hepatocellular carcinoma.

We performed whole exome sequencing (WES) and microarray analysis to detect somatic variants and copy number alterations (CNAs) for underlying mechanisms in a case series of hepatocellular carcinoma (HCC) with paired DNA samples from tumor and adjacent nontumor tissues. Clinicopathologic findings based on Edmondson-Steiner (E-S) grading, Barcelona-Clinic Liver Cancer (BCLC) stages, recurrence, and survival status and their associations with tumor mutation burden (TMB) and CNA burden (CNAB) were evaluated. WES from 36 cases detected variants in the TP53, AXIN1, CTNNB1, and SMARCA4 genes, amplifications of the AKT3, MYC, and TERT genes, and deletions of the CDH1, TP53, IRF2, RB1, RPL5, and PTEN genes. These genetic defects affecting the p53/cell cycle control, PI3K/Ras, and ß-catenin pathways were observed in approximately 80% of cases. A germline variant in the ALDH2 gene was detected in 52% of the cases. Significantly higher CNAB in patients with poor prognosis by E-S grade III, BCLC stage C, and recurrence than patients with good prognosis by grade III, stage A, grade III and nonrecurrence was noted. Further analysis on a large case series to correlate genomic profiling with clinicopathologic classifications could provide evidence for diagnostic interpretation, prognostic prediction, and target intervention on involved genes and pathways.

Phonon polaritons in van der Waals polar heterostructures for broadband strong light-matter interactions.

Phonon polaritons in polar crystals have recently gained significant attention due to their remarkable confinement and enhancement of electromagnetic fields, low group velocities, and low losses. However, these unique properties, resulting from the coupling between photons and lattice vibrations, exhibit limited spectral responses that may hinder their practical applications. Here, we propose and experimentally demonstrate that polar van der Waals heterostructures can integrate their polar constituents to enable broadband phonon polariton responses. A polar heterostructure is created by simply transferring thin flakes of two polar van der Waals materials, hexagonal boron nitride (hBN) and α-phase molybdenum trioxide (α-MoO3), onto a polar quartz substrate. Direct infrared nanoimaging experiments show that this integrated heterostructure supports phonon polaritons in a broadband infrared spectral range from 800 to 1700 cm-1. Further, numerical calculations predict vibrational strong coupling for a few molecule monolayers with multiple molecular absorption modes and phonon polaritons in the heterostructure. Our findings suggest that broadband phonon polariton responses in van der Waals integrated heterostructures have the potential to pave the way for the development of broadband and integrated infrared devices of molecular sensing, signal processing, and energy control.

Observation of directional leaky polaritons at anisotropic crystal interfaces.

Extreme anisotropy in some polaritonic materials enables light propagation with a hyperbolic dispersion, leading to enhanced light-matter interactions and directional transport. However, these features are typically associated with large momenta that make them sensitive to loss and poorly accessible from far-field, being bound to the material interface or volume-confined in thin films. Here, we demonstrate a new form of directional polaritons, leaky in nature and featuring lenticular dispersion contours that are neither elliptical nor hyperbolic. We show that these interface modes are strongly hybridized with propagating bulk states, sustaining directional, long-range, sub-diffractive propagation at the interface. We observe these features using polariton spectroscopy, far-field probing and near-field imaging, revealing their peculiar dispersion, and - despite their leaky nature - long modal lifetime. Our leaky polaritons (LPs) nontrivially merge sub-diffractive polaritonics with diffractive photonics onto a unified platform, unveiling opportunities that stem from the interplay of extreme anisotropic responses and radiation leakage.

Estimation on risk of spontaneous abortions by genomic disorders from a meta-analysis of microarray results on large case series of pregnancy losses.

A meta-analysis on seven large case series (>1000 cases) of chromosome microarray analysis (CMA) on products of conceptions (POC) evaluated the diagnostic yields of genomic disorders and syndromic pathogenic copy number variants (pCNVs) from a collection of 35,130 POC cases. CMA detected chromosomal abnormalities and pCNVs in approximately 50% and 2.5% of cases, respectively. The genomic disorders and syndromic pCNVs accounted for 31% of the detected pCNVs, and their incidences in POC ranged from 1/750 to 1/12,000. The newborn incidences of these genomic disorders and syndromic pCNVs were estimated in a range of 1/4000 to 1/50,000 live births from population genetic studies and diagnostic yields of a large case series of 32,587 pediatric patients. The risk of spontaneous abortion (SAB) for DiGeorge syndrome (DGS), Wolf-Hirschhorn syndrome (WHS), and William-Beuren syndrome (WBS) was 42%, 33%, and 21%, respectively. The estimated overall risk of SAB for major genomic disorders and syndromic pCNVs was approximately 38%, which was significantly lower than the 94% overall risk of SAB for chromosomal abnormalities. Further classification on levels of risk of SAB to high (>75%), intermediate (51%-75%), and low (26%-50%) for known chromosomal abnormalities, genomic disorders, and syndromic pCNVs could provide evidence-based interpretation in prenatal diagnosis and genetic counseling.

A mouse model for X-linked Alport syndrome induced by Del-ATGG in the Col4a5 gene.

Alport syndrome (AS) is an inherited glomerular basement membrane (GBM) disease leading to end-stage renal disease (ESRD). X-linked AS (XLAS) is caused by pathogenic variants in the COL4A5 gene. Many pathogenic variants causing AS have been detected, but the genetic modifications and pathological alterations leading to ESRD have not been fully characterized. In this study, a novel frameshift variant c.980_983del ATGG in the exon 17 of the COL4A5 gene detected in a patient with XLAS was introduced into a mouse model in by CRISPR/Cas9 system. Through biochemical urinalysis, histopathology, immunofluorescence, and transmission electron microscopy (TEM) detection, the clinical manifestations and pathological alterations of Del-ATGG mice were characterized. From 16 weeks of age, obvious proteinuria was observed and TEM showed typical alterations of XLAS. The pathological changes included glomerular atrophy, increased monocytes in renal interstitial, and the absence of type IV collagen α5. The expression of Col4a5 was significantly decreased in Del-ATGG mouse model. Transcriptomic analysis showed that differentially expressed genes (DEGs) accounted for 17.45% (4,188/24003) of all genes. GO terms indicated that the functions of identified DEGs were associated with cell adhesion, migration, and proliferation, while KEGG terms found enhanced the degradation of ECM, amino acid metabolism, helper T-cell differentiation, various receptor interactions, and several important pathways such as chemokine signaling pathway, NF-kappa B signaling pathway, JAK-STAT signaling pathway. In conclusion, a mouse model with a frameshift variant in the Col4a5 gene has been generated to demonstrate the biochemical, histological, and pathogenic alterations related to AS. Further gene expression profiling and transcriptomic analysis revealed DEGs and enriched pathways potentially related to the disease progression of AS. This Del-ATGG mouse model could be used to further define the genetic modifiers and potential therapeutic targets for XLAS treatment.

Broadband hyperbolic thermal metasurfaces based on the plasmonic phase-change material In3SbTe2.

Thermal radiation modulation facilitated by phase change materials (PCMs) needs a large thermal radiation contrast in broadband as well as in a non-volatile phase transition, which are only partially satisfied by conventional PCMs. In contrast, the emerging plasmonic PCM In3SbTe2 (IST) that undergoes a non-volatile dielectric-to-metal phase transition during crystallization offers a fitting solution. Here, we have prepared IST-based hyperbolic thermal metasurfaces and demonstrated their capabilities to modulate thermal radiation. By laser-printing crystalline IST gratings with different fill factors on amorphous IST films, we have achieved multilevel, large-range, and polarization-dependent control of the emissivity modulation (0.07 for the crystalline phase and 0.73 for the amorphous phase) over a broad bandwidth (8-14 µm). With the convenient direct laser writing technique that supports large-scale surface patterning, we have also demonstrated promising applications of thermal anti-counterfeiting with hyperbolic thermal metasurfaces.

Gate-tunable negative refraction of mid-infrared polaritons.

Negative refraction provides a platform to manipulate mid-infrared and terahertz radiation for molecular sensing and thermal emission applications. However, its implementation based on metamaterials and plasmonic media presents challenges with optical losses, limited spatial confinement, and lack of active tunability in this spectral range. We demonstrate gate-tunable negative refraction at mid-infrared frequencies using hybrid topological polaritons in van der Waals heterostructures. Specifically, we visualize wide-angle negatively refracted polaritons in α-MoO3 films partially decorated with graphene, undergoing reversible planar nanoscale focusing. Our atomically thick heterostructures weaken scattering losses at the interface while enabling an actively tunable transition of normal to negative refraction through electrical gating. We propose polaritonic negative refraction as a promising platform for infrared applications such as electrically tunable super-resolution imaging, nanoscale thermal manipulation, enhanced molecular sensing, and on-chip optical circuitry.

Real-space nanoimaging of hyperbolic shear polaritons in a monoclinic crystal.

Various optical crystals possess permittivity components of opposite signs along different principal directions in the mid-infrared regime, exhibiting exotic anisotropic phonon resonances. Such materials with hyperbolic polaritons-hybrid light-matter quasiparticles with open isofrequency contours-feature large-momenta optical modes and wave confinement that make them promising for nanophotonic on-chip technologies. So far, hyperbolic polaritons have been observed and characterized in crystals with high symmetry including hexagonal (boron nitride), trigonal (calcite) and orthorhombic (α-MoO3 or α-V2O5) crystals, where they obey certain propagation patterns. However, lower-symmetry materials such as monoclinic crystals were recently demonstrated to offer richer opportunities for polaritonic phenomena. Here, using scanning near-field optical microscopy, we report the direct real-space nanoscale imaging of symmetry-broken hyperbolic phonon polaritons in monoclinic CdWO4 crystals, and showcase inherently asymmetric polariton excitation and propagation associated with the nanoscale shear phenomena. We also introduce a quantitative theoretical model to describe these polaritons that leads to schemes to enhance crystal asymmetry via the damping loss of phonon modes. Ultimately, our findings show that polaritonic nanophotonics is attainable using natural materials with low symmetry, favouring a versatile and general way to manipulate light at the nanoscale.

Guided spiraling phonon polaritons in rolled one-dimensional MoO3 nanotubes.

Polaritons in reduced-dimensional materials, such as nanowire, nanoribbon and rolled nanotube, usually provide novel avenues for manipulating electromagnetic fields at the nanoscale. Here, we theoretically propose and study hyperbolic phonon polaritons (HPhPs) with rolled one-dimensional molybdenum trioxide (MoO3) nanotube structure. We find that the HPhPs in rolled MoO3 nanotubes exhibit low propagation losses and tunable electromagnetic confinement along the rolled direction. By rolling the twisted bilayer MoO3, we successfully achieve a canalized phonon polaritons mode in the rolled nanotube, enabling their propagation in a spiraling manner along the nanotube. Our findings demonstrate the considerable potential of the rolled MoO3 nanotubes as promising platforms for various applications in light manipulation and nanophotonics circuits, including negative refraction, waveguiding and routing at the ultimate scale.

The past, present, and future for constitutional ring chromosomes: A report of the international consortium for human ring chromosomes.

Human ring chromosomes (RCs) are rare diseases with an estimated newborn incidence of 1/50,000 and an annual occurrence of 2,800 patients globally. Over the past 60 years, banding cytogenetics, fluorescence in situ hybridization (FISH), chromosome microarray analysis (CMA), and whole-genome sequencing (WGS) has been used to detect an RC and further characterize its genomic alterations. Ring syndrome featuring sever growth retardation and variable intellectual disability has been considered as general clinical presentations for all RCs due to the cellular losses from the dynamic mosaicism of RC instability through mitosis. Cytogenomic heterogeneity ranging from simple complete RCs to complex rearranged RCs and variable RC intolerance with different relative frequencies have been observed. Clinical heterogeneity, including chromosome-specific deletion and duplication syndromes, gene-related organ and tissue defects, cancer predisposition to different types of tumors, and reproductive failure, has been reported in the literature. However, the patients with RCs reported in the literature accounted for less than 1% of its occurrence. Current diagnostic practice lacks laboratory standards for analyzing cellular behavior and genomic imbalances of RCs to evaluate the compound effects on patients. Under-representation of clinical cases and lack of comprehensive diagnostic analysis make it a challenge for evidence-based interpretation of clinico-cytogenomic correlations and recommendation of follow-up clinical management. Given recent advancements in genomic technologies and organized efforts by international collaborations and patient advocacy organizations, the prospective of standardized cytogenomic diagnosis and evidence-based clinical management for all patients with RCs could be achieved at an unprecedented global scale.

Prenatal and postnatal diagnosis of Phelan-McDermid syndrome: A report of 21 cases from a medical center and review of the literature.

Background: Phelan-McDermid syndrome (PMS), caused by deletions at 22q13.3 and pathogenic variants in the SHANK3 gene, is a rare developmental disorder characterized by hypotonia, developmental delay (DD), intellectual disability (ID), autism spectrum disorder (ASD), dysmorphic features, absence of or delayed language, and other features. Methods: Conventional karyotyping, chromosomal microarray analysis (CMA), and whole exome sequencing (WES) have been used to detect genetic defects causing PMS. We summarized the genetic and clinical findings from prenatal to postnatal stages of detected cases of PMS and mapped potential candidate haploinsufficient genes for deletions of 22q13. This study aimed to summarize the laboratory findings, genetic defects, and genotype-phenotype correlations for Chinese patients with PMS. Results: Seven prenatal cases and fourteen postnatal cases were diagnosed with PMS in our center. Thirteen cases had a deletion ranging in size from 69 to 9.06 Mb at 22q13.2-q13.33, and five cases had a pathogenic variant or an intragenic deletion in the SHANK3 gene. Three familial cases with a parental carrier of a balanced translocation were noted. A review of the literature noted another case series of 29 cases and a report of five cases of PMS in China. Genotype-phenotype correlations confirmed haploinsufficiency of the SHANK3 gene for PMS and suggested other candidate haploinsufficient genes TNFRSFI3C and NFAM1 genes for immunological features and TCF20, SULT4A1, PARVB, SCO2, and UPK3A genes for intellectual impairment and behavioral abnormality, neurological features, macrocephaly/hypotonia, oculopathy, and renal adysplasia, respectively. Conclusion: Indications for prenatal diagnosis of PMS are not specific, and approximately 85% prenatally diagnosed PMS elected termination of pregnancies after genetic counseling. For postnatal cases, 62.5% were caused by a deletion at 22q13 and 37.5% were caused by a pathogenic variant or an intragenic deletion in the SHANK3 gene. Approximately 6.7% of cases with a deletion were familial, and almost all pathogenic variants were de novo. Combined karyotype, CMA, and WES should be performed to increase the diagnostic yield. The identification of other candidate haploinsufficient genes in deletions of 22q13.2-q13.33 could relate to more severe dysmorphic features, neurologic defects, and immune deficiency. These results provided evidence for diagnostic interpretation, genetic counseling, and clinical management for the Chinese cases of PMS.