Differential responses in the mirror neuron system during imitation of individual emotional facial expressions and association with autistic traits.

The mirror neuron system (MNS), including the inferior frontal gyrus (IFG), inferior parietal lobule (IPL) and superior temporal sulcus (STS) plays an important role in action representation and imitation and may be dysfunctional in autism spectrum disorder (ASD). However, it's not clear how these three regions respond and interact during the imitation of different basic facial expressions and whether the pattern of responses is influenced by autistic traits. Thus, we conducted a natural facial expression (happiness, angry, sadness and fear) imitation task in 100 healthy male subjects where expression intensity was measured using facial emotion recognition software (FaceReader) and MNS responses were recorded using functional near-infrared spectroscopy (fNIRS). Autistic traits were measured using the Autism Spectrum Quotient questionnaire. Results showed that imitation of happy expressions produced the highest expression intensity but a small deactivation in MNS responses, suggesting a lower processing requirement compared to other expressions. A cosine similarity analysis indicated a distinct pattern of MNS responses during imitation of each facial expression with functional intra-hemispheric connectivity between the left IPL and left STS being significantly higher during happy compared to other expressions, while inter-hemispheric connectivity between the left and right IPL differed between imitation of fearful and sad expressions. Furthermore, functional connectivity changes during imitation of each different expression could reliably predict autistic trait scores. Overall, the results provide evidence for distinct patterns of functional connectivity changes between MNS regions during imitation of different emotions which are also associated with autistic traits.

Oral Oxytocin Facilitates Responses to Emotional Faces in Reward and Emotional-Processing Networks in Females.

INTRODUCTION: Oxytocin (OXT) is proposed as a potential therapeutic peptide for social dysfunction due to its modulatory actions on socioemotional regulation in humans. While the majority of studies have used intranasal OXT administration, we have recently shown that oral (lingual spray), but not intranasal, administration can significantly enhance activity of the brain reward system in response to emotional faces in males; however, its effects on females are unknown. METHODS: Seventy healthy females participated in the current randomized, placebo-controlled, pharmaco-imaging clinical trial, and the results were compared with our previous data from 75 males who underwent the same protocol. Participants were randomly assigned to OXT (24 IU) or placebo (PLC) groups and completed an implicit emotional face paradigm (angry/fear/happy/neutral) where they were only required to identify face gender. RESULTS: In line with previous results in males, oral OXT significantly increased plasma OXT concentration changes and enhanced putamen responses to all emotional faces compared to PLC in females. Additionally, OXT increased left amygdala activity to happy and angry faces and enhanced putamen-superior temporal gyrus functional coupling during processing of happy faces in females which was significantly different from males. CONCLUSION: Our findings suggest that oral OXT enhances responses in both reward and emotional-processing networks in females as well as males, and additionally, in females, it strengthens coupling between reward and social cognition regions.

Infrequent Intranasal Oxytocin Followed by Positive Social Interaction Improves Symptoms in Autistic Children: A Pilot Randomized Clinical Trial.

INTRODUCTION: There are currently no approved drug interventions for social behavior dysfunction in autism spectrum disorder (ASD). Previous trials investigating effects of daily intranasal oxytocin treatment have reported inconsistent results and have not combined it with positive social interaction. However, in two preclinical studies we established that treatment every other day rather than daily is more efficacious in maintaining neural and behavioral effects by reducing receptor desensitization. OBJECTIVE: We aimed to establish whether a 6-week intranasal oxytocin compared with placebo treatment, followed by a period of positive social interaction, would produce reliable symptom improvements in children with ASD. METHODS: A pilot double-blind, randomized, crossover design trial was completed including 41 children with ASD aged 3-8 years. Primary outcomes were the Autism Diagnostic Observation Schedule-2 (ADOS-2) and social responsivity scale-2 (SRS-2). Secondary measures included cognitive, autism- and caregiver-related questionnaires, and social attention assessed using eye-tracking. RESULTS: Significant improvements were found for oxytocin relative to placebo in primary outcome measures (total ADOS-2 and SRS-2 scores, ps < 0.001) and in behavioral adaptability and repetitive behavior secondary measures. Altered SRS-2 scores were associated with increased saliva oxytocin concentrations. Additionally, oxytocin significantly increased time spent viewing dynamic social compared to geometric stimuli and the eyes of angry, happy, and neutral expression faces. There were no adverse side effects of oxytocin treatment. CONCLUSIONS: Overall, results demonstrate that a 6-week intranasal oxytocin treatment administered every other day and followed by positive social interactions can improve clinical, eye tracking, and questionnaire-based assessments of symptoms in young autistic children.

Complete mitochondrial genome analysis and molecular phylogenetic implications of Kennelia xylinana (Lepidoptera: Tortricidae).

Kennelia is a small genus in Tortricidae that is distributed in the Oriental and Palaearctic regions, and its taxonomic position within the subfamily Olethreutinae is controversial. For a comprehensive understanding of the genus, we sequenced the mitogenome of Kennelia xylinana, the type species of Kennelia, and Ancylis unculana, a species of Enarmoniini; analyzed the mitogenome characteristics of K. xylinana; and explored its phylogenetic position. Similar to other members of Lepidoptera, the mitogenome of K. xylinana is 15,762-bp long and consists of 13 protein-coding genes (PCGs), two ribosomal RNA genes, 22 transfer RNA genes, and a noncoding control region. In particular, we found a structure (TATAATTAATAA)11 in the middle of the AT-rich region. Based on the Bayesian inference and maximum likelihood analyses of the 13 PCGs of 40 tortricid species, representing 8 tribes of 2 subfamilies, K. xylinana was clustered with two members of Enarmoniini, A. unculana and Loboschiza koenigiana, and formed highly supported monophyly. The results indicate that Kennelia should be placed in the tribe Enarmoniini.

Expression profile of long noncoding RNAs in children with systemic lupus erythematosus: a microarray analysis.

OBJECTIVES: Long noncoding RNAs (lncRNAs) are reported to play crucial roles in several physiological and biological processes. However, knowledge of lncRNAs in children with systemic lupus erythematosus (cSLE) remains limited. We investigate lncRNA expression profiling of cSLE and explore the potential function of lncRNAs. METHODS: LncRNA and mRNA microarrays were performed to identify changes in lncRNA and mRNA expression between children with SLE and paired healthy children. Quantitative polymerase chain reaction (qPCR) validated these results. A Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to explore the potential lncRNA function. RESULTS: A comparison between children with SLE and paired healthy children revealed that 1042 lncRNAs and 1162 mRNAs were differentially expressed. By using gene co-expression network analysis, we constructed a complex lncRNA target network consisting of 817 matched lncRNA-mRNA pairs for 309 differentially expressed lncRNAs and 210 differentially expressed mRNAs. The results of further GO and KEGG pathway analyses indicated that lncRNAs were involved mainly in pathways with crucial pathobiological relevance in SLE. CONCLUSIONS: We firstly characterised the expression profiles of lncRNA and mRNA in children with SLE and propose herein their possible roles in the pathogenesis of SLE. These results provide novel insights into the mechanisms of SLE pathogenesis and may serve as diagnostic biomarkers for SLE therapy.

Regulation mechanism and research progress of MeCP2 in Rett syndrome.

Rett syndrome (RTT) is an X-linked neurodevelopmental disease accountable for some of the severe mental retardation of females. Mutations in the gene encoding mythyl-CpG-binding protein 2, MeCP2, which acts as a suppressor of gene expression, are the primary genetic pathological change of RTT. Insufficient binding of MeCP2 with methylated DNA disrupts the proper expression of target genes and results in brain dysfunction. Currently, the proper role MeCP2 played in the process of brain development and the occurrence of RTT remain elusive. In this review, we summarize both the MECP2 gene and MeCP2 protein, with highlight upon their structures, functions and more importantly their regulatory mechanisms at the molecular level so as to elucidate the mechanisms underlying the pathogenesis of RTT.

Antennal excision reveals disparate olfactory expression patterns within castes in Reticulitermes aculabialis (Isoptera: Rhinotermitidae).

In lower termites, which exhibit a high degree of compound eye degradation or absence, antennae play a pivotal role in information acquisition. This comprehensive study investigates the olfactory system of Reticulitermes aculabialis, spanning five developmental stages and three castes. Initially, we characterize the structures and distribution of antennal sensilla across different developmental stages. Results demonstrate variations in sensilla types and distributions among stages, aligning with caste-specific division of labor and suggesting their involvement in environmental sensitivity detection, signal differentiation, and nestmate recognition. Subsequently, we explore the impact of antennal excision on olfactory gene expression in various caste categories through transcriptomics, homology analysis, and expression profiling. Findings reveal that olfactory genes expression is influenced by antennal excision, with outcomes varying according to caste and the extent of excision. Finally, utilizing fluorescence in situ hybridization, we precisely localize the expression sites of olfactory genes within the antennae. This research reveals the intricate and adaptable nature of the termite olfactory system, highlighting its significance in adapting to diverse ecological roles and demands of social living.

A clustering approach identifies an Autism Spectrum Disorder subtype more responsive to chronic oxytocin treatment.

Over the last decade, a number of clinical trials have reported effects of chronic treatment with intranasal oxytocin on autistic symptoms but with inconsistent findings. Autism is a heterogeneous disorder and one factor which may influence treatment outcome is whether a subtype of individuals is more sensitive to oxytocin. In a recent cross-over trial on 41 young autistic children we reported that 44% showed a reliable improvement in clinical symptoms (Autism Diagnostic Observation Schedule, ADOS-2) after a placebo-controlled, 6-week intranasal oxytocin intervention where treatment was given every other day followed by a period of positive social interaction. In the current re-assessment of the data, we used an unsupervised data-driven cluster analysis approach to identify autism subtypes using 23 different demographic, social subtype, endocrine, eye-tracking and clinical symptom measures taken before treatment and this revealed an optimum of two different subtypes. We then assessed the proportion of identified responders to oxytocin and found that while 61.5% of one subtype included responders only 13.3% of the other did so. During the placebo phase there was no difference between the two subtypes for the small proportion of responders (19.2% vs 6.7%). This oxytocin-sensitive subtype also showed overall significant post-treatment clinical and eye-tracking measure changes. The oxytocin-sensitive subtype was primarily characterized at baseline by lower initial clinical severity (ADOS-2) and greater interest in the eye-region of emotional faces. These features alone were nearly as efficient in identifying the two subtypes as all 23 baseline measures and this easy-to-conduct approach may help rapidly and objectively screen for oxytocin responders. Future clinical trials using oxytocin interventions may therefore achieve greater success by focusing on children with this specific autism subtype and help develop individualized oxytocin intervention.

Implications of mosquito metabolism on vector competence.

Mosquito-borne diseases (MBDs) annually kill nearly half a million people. Due to the lack of effective vaccines and drugs on most MBDs, disease prevention relies primarily on controlling mosquitoes. Despite huge efforts having been put into mosquito control, eco-friendly and sustainable mosquito-control strategies are still lacking and urgently demanded. Most mosquito-transmitted pathogens have lost the capacity of de novo nutrition biosynthesis, and rely on their vertebrate and invertebrate hosts for sustenance during the long-term obligate parasitism process. Therefore, a better understanding of the metabolic interactions between mosquitoes and pathogens will contribute to the discovery of novel metabolic targets or regulators that lead to reduced mosquito populations or vector competence. This review summarizes the current knowledge about the effects of mosquito metabolism on the transmission of multiple pathogens. We also discuss that research in this area remains to be explored to develop multiple biological prevention and control strategies for MBDs.

Regional superficial amygdala resting-state functional connectivity in adults infers childhood maltreatment severity.

Background: Childhood maltreatment (CM) is a potential risk factor for some neuropsychiatric disorders in adulthood (e.g. depression and anxiety) and alters trajectories of brain development. Accumulating evidence suggests that functional connectivity of the limbic system, especially the amygdala, is highly associated with childhood maltreatment, although not all studies have found this. These inconsistent results may be due to differential alterations of amygdala resting-state functional connectivity (rsFC) following childhood maltreatment. Objective: Our aim was to investigate the relationship between the rsFC of amygdala subregions and CM severity, as well as to develop a stable rsFC-based model for inferring the severity of CM. Methods: In this study, we employed the Childhood Trauma Questionnaire (CTQ) to assess CM severity in each individual. We explored the relationship between the rsFC of amygdala subregions (i.e. centromedial -CMA, basolateral -BLA, superficial-SFA amygdala) and CM experience in a discovery dataset of n = 110 healthy Chinese participants by linear multiple regression analysis. Subsequent dimensional and categorical approach were performed to elucidate the relationship between rsFCs and CM severity and CM subtypes, respectively. A support vector regression model was then conducted to validate the associations between rsFCs and total CTQ scores. Moreover, we also verified the model into another independent replication dataset (n = 38). Results: Our findings suggested that childhood maltreatment was negatively associated with rsFC between the right superficial amygdala and perigenual anterior cingulate cortex (pgACC)/postcentral gyrus (PCG) but not the other two amygdala subregions. Moreover, SFA-pgACC coupling was more associated with physical neglect whereas the SFA-PCG was more related to emotional neglect. In addition, supervised machine learning confirmed that using these two rsFCs as predictors could stably estimate continuous maltreatment severity in both discovery and replication datasets. Conclusion: The current study supports that the rsFCs of superficial amygdala are related to childhood maltreatment and which may be a potential biomarker for the effects of childhood maltreatment-related psychiatric disorders (i.e. depression and anxiety).

The complete mitochondrial genome of Clepsis pallidana (Lepidoptera: Tortricidae) with phylogenetic implications.

The leaf roller, Clepsis pallidana (Fabricius, 1776) (Lepidoptera: Tortricidae), is an important pest of many crops in China. The circular genome is 15,679 bp in length, consisting of 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and a non-coding AT-rich region. The base composition of the whole mitogenome is 41.2% A, 40.1% T, 11.1% C, and 7.7% G, which shows a strong AT bias. Phylogenetic analysis based on 13 PCGs showed that C. pallidana was closely related to Epiphyas postvittana and clustered within Archipini clade, which was consistent with the traditional classification.

[Factors influencing the bone mineral density in preterm infants].

OBJECTIVE: To study the bone mineral development and the factors influencing the development in preterm infants. METHODS: Ninety preterm and 90 term infants followed up by the child health care service were randomly enrolled. Tibia quantitative ultrasound measurements were used to evaluate bone mineral density described as supersonic speed of sound (SOS) and Z scores at 6 months old (corrected gestational age for preterm infants). The factors influencing bone mineral development were investigated by questionnaire. RESULTS: The SOS values and Z scores in term infants were significantly higher than those in preterm infants at 6 months old. In the preterm group, the SOS values and Z scores were significantly different in infants with different birth weights or gestational ages (P<0.05). The SOS values in preterm infants with different weaning time were significantly different. The Z scores in female preterm infants were significantly higher than that in males (P<0.05). Multiple regression analysis indicated that weaning time and daily time of outdoor activities were independent factors influencing SOS values in preterm infants. CONCLUSIONS: It is helpful to promote bone mineral development by an appropriate weaning time or increasing the time of outdoor activities in preterm infants.

The genus Syntozyga Lower (Lepidoptera, Tortricidae) in China, with descriptions of two new species.

Species of the genus Syntozyga Lower, 1901 (Lepidoptera, Tortricidae, Olethreutinae) from China are studied. Syntozyga apicispinata sp. nov. and S. similispirographa sp. nov. are described, S. pedias (Meyrick, 1920) is recorded for the first time from China, and S. spirographa (Diakonoff, 1968) is newly recorded from the Chinese mainland. Adults and genitalia are illustrated, and a distribution map of the Chinese species is given. Keys to identify the Chinese species of Syntozyga are provided. Species of the genus are well clustered in a neighbor-joining tree based on the sequence data of the COI gene. COI sequences corresponding to the new species and S. spirographa (Diakonoff, 1968) are submitted to BOLD.

[Meta analysis of lactic acid bacteria as probiotics for the primary prevention of infantile eczema].

OBJECTIVE: To determine whether lactic acid bacteria as probiotics is efficacious in the primary prevention of infantile eczema or atopic eczema. METHODS: For this meta analysis of randomized controlled trials (RCT) describing the efficacy of probiotics in infants with eczema or atopic eczema at ages of ≤2 years, a comprehensive search in the databases was performed up to January 2010. Three reviewers independently evaluated the studies for methodological qualities. RevMan 5.0.2 software was used for meta analysis. RESULTS: Twelve RCTs on the preventive effects of lactic acid bacteria as probiotics on infantile eczema were included, and 7 of the 12 RCTs reported the preventive effect of lactic acid bacteria on atopic eczema. The meta analysis showed that there was an overall significant reduction in infantile eczema and atopic eczema favoring lactic acid bacteria compared with placebo. The relative risk (RR) ratios for eczema and atopic eczema were 0.80 (95%CI: 0.70-0.90; P<0.01) and 0.78 (95%CI: 0.64-0.97; P<0.01), respectively. Lactic acid bacteria combined with other probiotics decreased significantly the incidence of eczema, with a RR ratio of 0.79 (95%CI: 0.68-0.93; P<0.01). The use of lactic acid bacteria alone did not result in a reduction in the incidence of eczema, with a RR ratio of 0.85 (95%CI: 0.69-1.05; P>0.05). CONCLUSIONS: The data from this meta analysis suggest that lactic acid probiotics combined with other probiotics play a role in the prevention of infantile eczema. There is insufficient evidence to recommend single use of lactic acid bacteria for prevention of eczema. Further studies are required to determine whether the findings are reproducible.

Effects of social stories intervention for children and adolescents with autism spectrum disorders: A protocol for a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder, which lacks specific medical treatment. Intervention is the key point of rehabilitation training for ASD. Social stories (SS) are a commonly used intervention practice in individuals with ASD. However, there is mixed evidence on the effectiveness of SS. Thus, the objective of this systematic review and meta-analysis is to assess studies of the effects of SS for children and adolescents with ASD. METHODS: To identify relevant studies, we will search PubMed, EMBASE, Cochrane Library, Web of Science, Google Scholar and trials registers (the World Health Organization International Clinical Trial Registration Platform, ClinicalTrials.gov, and Chinese Clinical Trial Register) from inception to May 2020. In addition, we will also perform handsearching of grey literature, such as conference proceedings and academic degree dissertations. Only the randomized control trials will be accepted, no matter what the languages they were reported. We will first focus on the effectiveness of the intervention on the behavior of the targets. Then we will do further analysis of the study design, including the length and intensity of intervention, the characteristics of participants and interveners, the methods of assessment, the place, the medium, and the economic feasibility. Two independent reviewers will carry out literature identification, data collection, and study quality assessment. Discrepancies will be resolved by a third reviewer. The Cochrane Risk of Bias Tool will be used to evaluate the risk of bias of the randomized controlled trials. Data analysis will be calculated using the STATA 13.0 software. RESULT: This study will offer new evidence whether the SS is an appropriate intervention of benefiting the children and adolescents with ASD, and to determine which factors affect the effectiveness of SS. CONCLUSION: The conclusion drawn from this systematic review will benefit the children and adolescents with ASD.

The complete mitochondrial genome of a leaf roller, Eudemis lucina (Lepidoptera: Tortricidae).

The leaf roller, Eudemis lucina, is a potential pest of Quercus in East Asia. In this study, we described the complete mitochondrial genome of this species by high-throughput sequencing. The mitochondrial genome is found to be a circular molecule of 16,056 bp in length, which consisted of 13 protein-coding genes (PCGs), 22 tRNA genes, 2 rRNA genes, and a non-coding control region (A + T-rich region). The A + T content is 80.5% for the whole mitogenome. All PCGs are initiated by ATN codons, except for COI which is initiated by the CGA codon. Eight PCGs use a typical stop codon of TAA, whereas the remaining PCGs use incomplete stop codon of T-- or TA-. The non-coding control region is 1013 bp and located between s-rRNA and Met-tRNA.

Complete mitochondrial genome of Phiaris dolosana (Lepidoptera: Tortricidae).

We describe the complete mitochondrial genome of Phiaris dolosana. It is 15,562 bp in length, and contains 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), and a 612 bp D-Loop. All PCGs start with ATN codon except for COI gene, which uses CGA as the initiation codon. Nine of 13 PCGs use a typical stop codon of TAA, the rest use incomplete stop codon of T or TA. Phylogenetic analysis of P. dolosana with other 17 leaf rollers is conducted with neighbor-joining method, the result is consistent with the conventional classification.

Microarray expression profile of circular RNAs and mRNAs in children with systemic lupus erythematosus.

BACKGROUND: Recently, it was reported that circular RNAs (circRNAs) play the crucial role in many physiological and biological processes and can be used as biomarkers. However, the information about circRNAs in children with systemic lupus erythematosus (SLE) is limited. The aim of this study is to determine the expression of circRNAs in children with SLE and investigate the significance of circRNA for diagnosing SLE. METHODS: Microarray profile of circRNAs and mRNAs was performed for identifying the changes in expression of circRNAs and mRNAs between children with SLE and healthy children. Quantitative polymerase chain reaction (qPCR) was used to confirm the results. Spearman correlation test was performed to assess the correlation between circRNAs and clinical variables. The receiver operating characteristic (ROC) curve was calculated for evaluating the diagnostic value. RESULTS: A comparison between the children with SLE and healthy children revealed that 348 circRNAs and 1162 mRNAs were expressed differentially. The authors constructed a complex circRNA target network consisting of 307 matched circRNA-mRNA pairs for 124 differentially expressed circRNAs (74 circRNAs were upregulated, and 50 circRNAs were downregulated) and 142 differentially expressed mRNAs (83 mRNAs were upregulated, and 59 mRNAs were downregulated) by using gene co-expression network analysis. The competing for endogenous RNA (ceRNA) network includes 42 differentially expressed circRNAs, 41 differentially expressed mRNAs, and 71 predicted miRNAs. Among these SLE patients, we detected that the hsa_circ_0021372 and hsa_circ_0075699 levels are associated with C3 and C4 levels in children with SLE. The hsa_circ_0057762 level is positively associated with the SLEDAI-2K score. The ROC curves of circRNAs showed that the levels of hsa_circ_0057762 (AUC 0.804, 95% CI 0.607-1.0, P = 0.02) and hsa_circ_0003090 (AUC 0.848, 95% CI 0.688-1.0, P = 0.008) could differentiate the patients with SLE from the healthy controls. CONCLUSIONS: We firstly characterized the expression profiles of circRNA and mRNA in children with SLE and propose herein their possible roles in the pathogenesis of SLE. These results provide novel insight into the mechanisms of SLE pathogenesis, and circRNAs may serve as useful biomarkers for SLE.

Detection of recurrent 4p16.3 microdeletion with 2p25.3 microduplication by multiplex ligation-dependent probe amplification and array comparative genomic hybridization in a fetus from a family with Wolf-Hirschhorn syndrome.

OBJECTIVE: We present prenatal diagnosis, genetic counseling, and molecular cytogenetic features of familial recurrence of Wolf-Hirschhorn syndrome (WHS). MATERIALS AND METHODS: A 31-year-old woman was referred to a hospital at 24 weeks of gestation because of abnormal ultrasound findings in the fetus. Her first child was a boy who had growth retardation, mental defect, and a distinctive facial appearance. Based on the conventional cytogenetic analysis, the combined use of multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (aCGH) facilitated the prenatal diagnosis and genetic counseling in the fetus. Results of the standard G-banging karyotype analysis of the fetus, the parents, and the boy were normal. RESULTS: The MLPA analysis revealed the same 4p microdeletion accompanied by 2p microduplication in the fetus and the boy. The aCGH analysis revealed a 3.57-Mb 4p16.3 microdeletion or arr [hg19] 4p16.3 (71,552-3,636,893) x1 in the fetus and a 3.29-Mb 4p16.3 microdeletion or arr [hg19] 4p16.3 (71,148-3,360,737) x1 in the boy. The 3.57-Mb 4p16.3 microdeletion encompassed 39 OMIM genes. The 3.29-Mb 4p16.3 microdeletion encompassed 36 OMIM genes. They both included LETM1 and WHSC1. The 2p25.3 microduplication was smaller than 666 kb and encompassed only one OMIM gene, ACP1. CONCLUSION: The combined use of MLPA and aCGH is an effective way to diagnose recurrent WHS. Although WHS is typically caused by a de novo deletion, prenatal diagnosis and genetic counseling are necessary in the next pregnancy in families that have suffered such cases.

Analyses of Genotypes and Phenotypes of Ten Chinese Patients with Wolf-Hirschhorn Syndrome by Multiplex Ligation-dependent Probe Amplification and Array Comparative Genomic Hybridization.

BACKGROUND: Wolf-Hirschhorn syndrome (WHS) is a contiguous gene syndrome that is typically caused by a deletion of the distal portion of the short arm of chromosome 4. However, there are few reports about the features of Chinese WHS patients. This study aimed to characterize the clinical and molecular cytogenetic features of Chinese WHS patients using the combination of multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (array CGH). METHODS: Clinical information was collected from ten patients with WHS. Genomic DNA was extracted from the peripheral blood of the patients. The deletions were analyzed by MLPA and array CGH. RESULTS: All patients exhibited the core clinical symptoms of WHS, including severe growth delay, a Greek warrior helmet facial appearance, differing degrees of intellectual disability, and epilepsy or electroencephalogram anomalies. The 4p deletions ranged from 2.62 Mb to 17.25 Mb in size and included LETM1, WHSC1, and FGFR3. CONCLUSIONS: The combined use of MLPA and array CGH is an effective and specific means to diagnose WHS and allows for the precise identification of the breakpoints and sizes of deletions. The deletion of genes in the WHS candidate region is closely correlated with the core WHS phenotype.