Prenatal Diagnosis of Fetuses with 4q35 Deletion: Case Series and Review of the Literature.

INTRODUCTION: 4q35 deletion is a rare chromosomal syndrome with a wide range of phenotypes, which can be challenging to detect through prenatal ultrasound. This study aimed to summarize the fetal phenotypes of patients with 4q35 deletion. CASE PRESENTATION: The study included four fetuses with 4q35 deletion, with detailed records of prenatal ultrasound and genetic testing results. These cases included following phenotypes, fetal growth restriction (FGR) (2/4), cystic hygroma (2/4), single umbilical artery (1/4), and fused kidney (1/4). One case was terminated, while the other three were born and showed no obvious abnormalities at the 1-year follow-up. Previous reports have described the fetal phenotype of 4q35 deletion in 6 patients from five families, with prenatal phenotypes including FGR (2/6), cardiac structural abnormalities (1/6), brain ventriculomegaly (1/6), oligohydramnios (1/6), and multicystic dysplastic kidneys (1/6). CONCLUSION: Overall, the phenotypes of fetuses with 4q35 deletion are diverse, with FGR potentially being a significant phenotype in these cases.

Diagnostic Potential of Complementation of MRI to Prenatal Ultrasound for Detecting Orofacial Clefts in High-Risk Fetuses: A Network Meta-Analysis.

OBJECTIVE: To compare the complementation of magnetic resonance imaging (MRI) to prenatal ultrasound (US) with prenatal US alone in detecting orofacial clefts in high-risk fetuses. DESIGN: A network meta-analysis. SETTING: Literature retrieval in PubMed, EMBASE, and Cochrane library, and meta-analysis based on STATA 14.0. PATIENTS: Fetuses were at high-risk for orofacial clefts. INTERVENTIONS: Prenatal US and the complementation of MRI to prenatal US. MAIN OUTCOME MEASURES: The pooled sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), diagnostic odds ratio (DOR), and area under the curve (AUC). RESULTS: Thirteen studies involving 776 patients were included. Direct meta-analysis showed that the complementation of MRI to prenatal US did not differ from prenatal US in detecting orofacial clefts if the type of orofacial clefts was not distinguished. Subgroup analysis showed that the specificity of prenatal US for the detection of isolated cleft palate (CP) was lower than that of the complementation of MRI to prenatal US. Furthermore, network meta-analysis consistently suggested a comparable diagnostic value between prenatal US and the complementation of MRI to prenatal US. Moreover, subgroup analysis showed that the specificity of prenatal US was significantly lower than that of complementation of MRI to prenatal US for the detection of isolated CP. CONCLUSIONS: MRI is more accurate than ultrasound in detecting cleft palate. Therefore, MRI should be offered if there is a fetus with a possible or ultrasound diagnosis of cleft palate, especially if the evaluation of cleft palate is deemed unsatisfactory after careful evaluation of the images.

[Prenatal genetic diagnosis for fetuses with anomalies revealed by fetal echocardiography].

OBJECTIVE: To carry out amniocyte karyotyping analysis and chromosomal microarray analysis (CMA) for women with anomalies revealed by fetal echocardiography. METHODS: From January 2019 to December 2021, genetic testing was carried out for 205 fetuses including 97 with soft marker anomalies and 108 with structural heart abnormalities. Among these, 138 only had abnormal fetal echocardiography, whilst 38 and 29 were complicated with extracardiac soft marker anomalies and extracardiac structural malformation, respectively. RESULTS: No significant difference was detected in the detection rate of genetic anomalies between fetuses with heart-related soft markers and those with abnormal heart structures (P > 0.05). Compared with those with abnormal fetal echocardiography alone, the detection rates of chromosomal aneuploidies in those with abnormal extracardiac soft markers or abnormal extracardiac structures were significantly higher (P < 0.05). Twenty-eight chromosomal aneuploidies (including a rare mosaicism), 2 balanced translocations and 1 supernumerary marker chromosome were detected by karyotyping analysis. Twenty-seven aneuploidies, 19 copy number variations (CNVs) and 1 uniparental disomy were detected by CMA. CONCLUSION: Prenatal diagnosis has attached great importance to the suggestive role of fetal heart-related soft markers, and chromosomal aneuploidies are more common among fetuses with abnormal extracardiac soft markers and extracardiac structural abnormalities. Chromosomal Karyotyping is useful for the detection of balanced translocations and mosaicisms. CMA is helpful for the detection of CNVs. Identification of the genetic causes can facilitate genetic counseling for the affected couples.

Up-regulation of long noncoding RNA LINC00858 is associated with poor prognosis in gastric cancer.

BACKGROUND: The present study aimed to investigated the expression pattern of long noncoding RNA LINC00858 (LINC00858) in gastric cancer (GC) patients and its feasibility as a new prognostic biomarker. METHODS: We examined LINC00858 expression in GC tissues and matched normal tissues from 189 patients using a quantitative reverse transcription-polymerase chain reaction. The correlations of LINC00858 levels in GC patients with clinicopathologic features were analyzed using a chi-squared test. The influence of LINC00858 on the overall survival rate of GC patients was precisely calculated using Kaplan-Meier methods (log rank tests). Multivariate Cox regression assays were carried out for the identification of the independent risk factors for GC. RESULTS: We observed that LINC00858 was distinctly up-regulated in GC tissues compared to adjacent non-tumor specimens (p < 0.01). Higher expression of LINC00858 in GC was found to be associated with TNM stage (p = 0.003) and lymphatic metastasis (p = 0.007). Using Kaplan-Meier assays, we found that patients with high expression levels of LINC00858 had a distinctly poor overall survival and disease-free survival compared to those with low expression levels of LINC00858 (p = 0.0102). Multivariate analyses confirmed that LINC00858 (p < 0.05) was an independent prognosis factor for GC patients. CONCLUSIONS: The data obtained in our study indicate that LINC00858 may be used as a novel prognostic indicator in GC patients.

Internal hernia beneath superior vesical artery after pelvic lymphadenectomy for cervical cancer: a case report and literature review.

BACKGROUND: The common complications of radical hysterectomy and pelvic lymphadenectomy usually include wound infection, hemorrhage or hematomas, lymphocele, uretheral injury, ileus and incisional hernias. However, internal hernia secondary to the orifice associated with the uncovered vessels after pelvic lymphadenectomy is very rare. CASE PRESENTATION: We report a case of internal hernia with intestinal perforation beneath the superior vesical artery that occurred one month after laparoscopic pelvic lymphadenectomy for cervical cancer. A partial ileum resection was performed and the right superior vesical artery was transected to prevent recurrence of the internal hernia. CONCLUSIONS: Retroperitonealization after the pelvic lymphadenectomy should be considered in patients with tortuous, elongated arteries which could be causal lesions of an internal hernia.

Regioselective Access to 3-Aryl-1-aminoisoquinolines via Nickel(I)-Catalyzed C-C and C-N Cascade Coupling Reactions from the Substituted 2-(Cyanomethyl)benzonitriles.

A novel and regioselective Ni(I) catalyzed C-C and C-N cascade coupling reactions has been developed. The cascade furnishes atom-economic access to 40 3-aryl-1-aminoisoquinolines. The regioselectivity of C(sp3)-cyano group over C(sp2)-cyano group was revealed and supported by mechanism studies as well as the preliminary density functional theory (DFT) calculations.

Discovery of 4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amines as potent, selective and orally bioavailable LRRK2 inhibitors.

Inhibition of LRRK2 kinase activity with small molecules has emerged as a potential novel therapeutic treatment for Parkinson's disease. Herein we disclose the discovery of a 4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amine series as potent LRRK2 inhibitors identified through a kinase-focused set screening. Optimization of the physicochemical properties and kinase selectivity led to the discovery of compound 7, which exhibited potent in vitro inhibition of LRRK2 kinase activity, good physicochemical properties and kinase selectivity across the kinome. Moreover, compound 7 was able to penetrate into the CNS, and in vivo pharmacology studies revealed significant inhibition of Ser935 phosphorylation in the brain of both rats (30 and 100 mg/kg) and mice (45 mg/kg) following oral administration.

Microwave-assisted synthesis of hydroxyl-containing isoquinolines by metal-free radical cyclization of vinyl isocyanides with alcohols.

A convenient microwave-assisted protocol for the synthesis of hydroxyl-containing isoquinolines from a metal-free radical cyclization reaction of vinyl isonitriles with alcohols was developed with moderate-to-excellent yields. Vinyl isonitriles are coupled with alkyl radicals through direct catalytic functionalization of the α sp3 C-H bond of alcohols. The methodology demonstrates a broad substrate scope, shows excellent functional group tolerance, is highly atom-economical and highly efficient, thus enabling the preparation of diverse potentially valuable hydroxyl-containing isoquinolines.

In vitro and in vivo effect of paclitaxel and cepharanthine co-loaded polymeric nanoparticles in gastric cancer.

PURPOSE: Response surface methodology (RSM) using the central composite rotatable design (CCRD) model was used to optimize the formulation of paclitaxel (PTX)-cepharanthine (CEP) nanoparticles for gastric cancer. METHODS: Nanoparticles were prepared using nanoprecipitation technique and optimized using central composite rotatable design response surface methodology (CCRD-RSM). Further the optimized nanoparticles were characterised for particle size (PS), zeta potential, entrapment efficiency (EE), drug loading efficiency (DL), anticancer potential against MKN45 (human gastric cancer) cells, in vivo tumor inhibition and survival analysis. RESULTS: Significant findings were the optimal formulation of polymer concentration of 48 mg, surfactant concentration of 45% and EE of 98.12%, DL of 15.61% and mean diameter of 198±4.7 nm. The encapsulation of PTX/CEP into nanoparticles retained the synergistic anticancer efficiency against MKN45 cells. In the in vivo evaluation, PTXsCEP nanoparticles delivered into mice by intravenous injection significantly improved the antitumor efficacy of PTX/CEP. Moreover, PTX/CEP co-loaded nanoparticles substantially increased the overall survival in an established MKN45-transplanted mouse model. CONCLUSION: These data are the first to demonstrate that PTX/CEP co-loaded nanoparticles increased the anticancer efficacy in cell lines and xenograft mouse model. Our results suggest that PTX/CEP coloaded nanoparticles could be a potential useful chemotherapeutic formulation for gastric cancer.

Targeted exome sequencing strategy (NeoEXOME) for Chinese newborns using a pilot study with 3423 neonates.

BACKGROUND: Newborn screening (NBS) aims to detect congenital anomalies, and next-generation sequencing (NGS) has shown promise in this aspect. However, the NBS strategy for monogenic inherited diseases in China remains insufficient. METHODS: We developed a NeoEXOME panel comprising 601 genes that are relevant to the Chinese population found through extensive research on available databases. An interpretation system to grade the results into positive (high-risk, moderate-risk, and low-risk genotypes), negative, and carrier according to the American College of Medical Genetics (ACMG) guidelines was also developed. We validated the panel to evaluate its efficacy by using data from the "1000 Genomes Project" and conducted a pilot multicenter study involving 3423 neonates. RESULTS: The NGS positive rate in the 1000 Genomes Project was 7.6% (23/301), whereas the rate was 12.0% in the multicenter study, including 3249 recruited neonates. Notably, in 200 neonates, positive per conventional NBS, 58.5% (69/118) showed results consistent with NGS. In the remaining 3049 neonates showing negative results in conventional NBS, 271 (8.9%) were positive per NGS, and nine of them were clinically diagnosed with diseases in the follow-up. CONCLUSION: We successfully designed a NeoEXOME panel for targeted sequencing of monogenic inherited diseases in NBS. The panel demonstrated high performance in the Chinese population, particularly for the early detection of diseases with no biochemical markers.

[Retracted] miR­206 inhibits cancer initiating cells by targeting EHF in gastric cancer.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the colony formation assay data shown in Figs. 2, 4 and 8 were strikingly similar to data that had already appeared in another article written by different authors at different research institutes [Chen W, Wang J, Liu S, Wang S, Cheng Y, Zhou W, Duan C and Zhang C: MicroRNA­361­3p suppresses tumor cell proliferation and metastasis by directly targeting SH2B1 in NSCLC. J Exp Clin Cancer Res 35: 76, 732516, 2016]. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 38: 1688­1694, 2017; DOI: 10.3892/or.2017.5794].

Degos disease with multiple intestinal perforations: A missed-opportunity case report and literature review.

Introduction: Degos disease, also known as malignant atrophic papulosis (MAP), is a rare systemic obstructive vascular disease with unknown pathophysiology, which can affect multiple systems, especially gastrointestinal tract and central nervous system. Intestinal perforations with MAP is associated with high mortality rate and ambiguous treatment outcomes. Case presentation: Here we report a missed-opportunity case of Degos disease characterized by generalized skin eruption and multiple intestinal perforations. Definite diagnosis of Degos disease was finally concluded after two exploratory laparotomy operations and skin biopsies. Due to the delayed diagnosis and treatment, the patient died after being discharged automatically in spite of application of aspirin and low-dose subcutaneous heparin. In view of such circumstances, we searched the Pubmed using "Degos [Title] OR Malignant Atrophic Papulosis [Title]" AND "perforation [Title] OR perforations [Title]" and make a detailed analysis of the result. Conclusions: Degos disease is a rare systemic obstructive vascular disease with unknown pathologic mechanism and unavailable treatment methods. Diagnosis is usually based on the presence of pathognomonic skin lesions and tissue biopsy. Gastrointestinal involvement can cause serious and lethal conditions with high mortality. Currently, how to achieve a satisfying prognosis of MAP with intestinal perforations becomes the most urgent problem in front of medical staff.

Evaluation of effect of empirical attack-preventive immunotherapies in neuromyelitis optica spectrum disorders: An update systematic review and meta -analysis.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system, which mainly involves the optic nerve and spinal cord. Frequent relapse can accumulate the degree of disability. At present, the main treatment options are immunosuppressants and blood purification. The first-line immunosuppressants for NMOSD are mainly rituximab (RTX), mycophenolate mofetil (MMF) and azathioprine (AZA). Therefore, we designed this systematic review and meta-analysis to evaluate the safety and effect of the above three drugs in the treatment of NMOSD patients. METHODS: The following Medical Subject Heading (MeSH) and related entry terms are used to search English literature in PubMed, MEDLINE and CENTRAL databases, respectively. MeSH include: Neuromyelitis optic and Rituximab or Azathioprine or Mycophenolate Mofetil; entry terms include: NMO Spectrum Disorder, NMO Spectrum Disorders, Neuromyelitis Optica (NMO) Spectrum Disorder, Neuromyelitis Optica Spectrum Disorders, Devic Neuromyelitis Optica, Neuromyelitis Optica, Devic, Devic's Disease, Devic Syndrome, Devic's Neuromyelitis Optica, Neuromyelitis Optica (NMO) Spectrum Disorders, CD20 Antibody, Rituximab CD20 Antibody, Mabthera, IDEC-C2B8 Antibody, GP2013, Rituxan, Mycophenolate Mofetil, Mofetil, Mycophenolate, Mycophenolic Acid, Morpholinoethyl Ester, Cellcept, Mycophenolate Sodium, Myfortic, Mycophenolate Mofetil Hydrochloride, Mofetil Hydrochloride, Mycophenolate, RS 61443, RS-61443, RS61443, azathioprine sodium, azathioprine sulfate (note: literature retrieval operators "AND" "OR" "NOT" are used to link MeSH with Entry Terms.) The literature search found a total of 3058 articles about rituximab, mycophenolate mofetil and azathioprine in the treatment of NMOSD, 63 of which were included in this study after a series of screening. RESULTS: 930,933,732 patients with NMOSD were enrolled, who had been treated with MMF, AZA and RTX, respectively. The pooled standardized mean difference (SMD) of EDSS before and after RTX treated was -0.58 (95%CI: -0.72, -0.44) (I2 = 0%, p = 0.477), before and after MMF treated was -0.47 (95%CI: -0.73, -0.21) (I2 = 85.6%, p<0.001), before and after AZA treated was -0.41 (95%CI: -0.60, -0.23) (I2 = 65.4%, p<0.001). there was no significant difference in the effect of the three drugs on reducing EDSS scores (RTX vs MMF, p = 0.522; RTX vs AZA, p = 0.214; MMF vs AZA, p = 0.732). The pooled standardized mean difference (SMD) of ARR before and after RTX treated was -1.45 (95%CI: -1.72, -1.18) (I2 = 72.4%, p<0.001), before and after MMF treated was -1.14 (95%CI: -1.31, -0.97) (I2 = 54.5%, p<0.001), before and after AZA treated was -1.11 (95%CI: -1.39, -0.83) (I2 = 83.4%, p<0.001). RTX significantly reduced ARR compared with the other two drugs (RTX vs MMF, p = 0.039; RTX vs AZA, p = 0.049; MMF vs AZA, p = 0.436). CONCLUSION: The results of this systematic review and meta-analysis showed that the treatment of NMOSD patients with RTX, MMF and AZA is associated with decreased number of relapses and disability improvement as well, and there was no significant difference in the effect of the three drugs on reducing EDSS scores, but RTX significantly reduced ARR compared with the other two drugs.

Identification of a novel mutation in CYBB gene in a Chinese neonate with X-linked chronic granulomatous disease: A case report.

RATIONALE: X-linked chronic granulomatous disease (X-CGD) is an X-linked recessive disorder of the Nicotinamide adenine dinucleotide phosphate oxidase system that can cause primary immunodeficiency. Mutations in the CYBB gene located in Xp21.1 were accounting for X-CGD disease. More than 600 mutations have been identified as the cause of X-CGD in various populations worldwide. PATIENT CONCERNS AND DIAGNOSIS: In this study, the proband suffered from elevated white blood cells (WBC, 23.65 × 109/L), mainly in neutral (16.4 × 109/L). The neutrophil oxidative index of the patient was 2.13, which was extremely low, whereas his mother was 69.0 (Ref >100). Next, next-generation sequencing of the primary immunodeficiency diseases -related gene panel was performed. One novel mutation was identified in the CYBB gene in the CGD case: c.55C>G in exon 2. The mutation was verified by Sanger sequencing. The mother of the patient was heterozygous for the c.55C>G mutation, and the father was normal. These mutations were not present in the 100 unrelated normal controls. INTERVENTIONS AND OUTCOMES: The patient died from severe and uncontrollable pulmonary infection at 3 months of age. LESSONS: The identification of these mutations in this study further expands the spectrum of known CYBB gene mutations and contributes to the genetic counseling and prenatal molecular diagnosis of X-CGD.

Dietary supplementation of ferrous glycinate improves intestinal barrier function by modulating microbiota composition in Cherry Valley ducks.

Ferrous glycinate (Fe-Gly) has been increasingly used as iron fortification in the diets of weaned piglets and broilers, but the effect of Fe-Gly on intestinal barrier function in meat ducks has not been well defined. This study therefore investigated the effect of Fe-Gly on apparent nutrient utilization, hematological indices, intestinal morphological parameters, intestinal barrier function and microbial composition in meat ducks. A total of 672 one-day-old Cherry Valley ducks were randomly divided into 6 treatments (8 replicates for each treatment and 14 ducks for each replicate) and fed diets with 0 (control), 30, 60, 90 and 120 mg/kg Fe-Gly or 120 mg/kg FeSO4 for 35 d. The results showed that diets supplemented with Fe-Gly significantly increased average daily gain (ADG), average daily feed intake (ADFI), hematocrit (HCT), mean cell volume (MCV), the apparent utilization of dry matter (DM) and metabolizable energy (ME), villus height (VH) and villus height-to-crypt depth ratio (V:C) (P < 0.05). Fe-Gly also significantly up-regulated barrier-related genes including zonula occludens-1 (ZO-1), zonula occludens-2 (ZO-2), mucin 2 (MUC2) and lysozyme (LYZ) (P < 0.05), and down-regulated the mRNA expression of claudin-2 (CLDN2) and occludin (OCLN) in the jejunum (P < 0.05). The 16S rRNA sequence analysis indicated that the diet with Fe-Gly had a higher relative abundance of Intestinimonas and Romboutsia (P < 0.05), which have an ability to produce short chain fatty acids (SCFAs), especially butyric acid. It also decreased the relative abundance of pathobiont, including Megamonas, Eubacterium_coprostanoligenes_group and Plebeius (P < 0.05). Additionally, diets supplemented with 120 mg/kg Fe-Gly significantly increased the apparent utilization of DM and ME (P < 0.05) and decreased the relative abundance of Megamonas_unclassified and Bacteroides_unclassified compared with those fed 120 mg/kg FeSO4 (P < 0.05). These results revealed that diets supplemented with Fe-Gly exerted a potent beneficial effect on physical, chemical, immune and microbial barriers, thereby improving the integrity of the intestinal structure, promoting the digestion and absorption of nutrients to a certain extent, and ultimately elevating the growth performance of ducks.

A synonymous mutation in PI4KA impacts the transcription and translation process of gene expression.

Phosphatidylinositol-4-kinase alpha (PI4KIIIα), encoded by the PI4KA gene, can synthesize phosphatidylinositol-4-phosphate (PI-4-P), which serves as a specific membrane marker and is instrumental in signal transduction. PI4KA mutations can cause autosomal recessive diseases involving neurological, intestinal, and immunological conditions (OMIM:619621, 616531, 619708). We detected sepsis, severe diarrhea, and decreased immunoglobulin levels in one neonate. Two novel compound heterozygous mutations, c.5846T>C (p.Leu1949Pro) and c.3453C>T (p.Gly1151=), were identified in the neonate from the father and the mother, respectively. Sanger sequencing and reverse transcription polymerase chain reaction (RT-PCR) for peripheral blood and minigene splicing assays showed a deletion of five bases (GTGAG) with the c.3453C>T variant at the mRNA level, which could result in a truncated protein (p.Gly1151GlyfsTer17). The missense mutation c.5846T>C (p.Leu1949Pro) kinase activity was measured, and little or no catalytic activity was detected. According to the clinical characteristics and gene mutations with functional verification, our pediatricians diagnosed the child with a combined immunodeficiency and intestinal disorder close to gastrointestinal defects and immunodeficiency syndrome 2 (GIDID2; OMIM: 619708). Medicines such as immunomodulators are prescribed to balance immune dysregulation. This study is the first report of a synonymous mutation in the PI4KA gene that influences alternative splicing. Our findings expand the mutation spectrum leading to PI4KIIIa deficiency-related diseases and provide exact information for genetic counseling.

Pyridazine-derived γ-secretase modulators.

SAR of a novel series of pyridazine-derived γ-secretase modulators is described. Compound 25 was found to be a potent modulator in vitro, which on further profiling, was found to decrease Aß42 and Aß40, and maintain the levels of total Aß. Furthermore, 25 demonstrated excellent pharmacokinetic parameters as well as good CNS penetration in the rat.

Pyridine-derived γ-secretase modulators.

SAR of a novel series of pyridine-derived γ-secretase modulators is described. Compound 5 was found to be a potent modulator in vitro, which on further profiling, was found to decrease Aß42 and Aß40, and maintain (or increase) the levels of total Aß. Furthermore, representative compounds 1 and 5 demonstrated in vivo efficacy to lower Aß42 in the brain without altering Notch processing in the peripheral.

Virtual Reality-Based Analysis of Pressure Ulcer Care Information Related to Medical Equipment for the Prevention of Pressure Ulcer Skin Foam Dressings in the Elderly.

As the standard of life has increased with the advancement of the time, there has been an increasing stress on healthcare with the aging diet, and pressure sores occur in elderly hospitalized subjects. Of course, the emergence of related medical devices, especially auxiliary foam dressings, is constantly improving. Pressure ulcers are extremely harmful to the elderly. The use of virtual reality technology to simulate the treatment of foam excipients is to test the role of medical devices in virtual reality. In particular, the use of foam dressings in the management of pressure deposits is the most relevant study for this paper, which reviews the relevant literature and conducts a thematic study on patients in a specific urban hospital. The relevant materials were designed, the experiments were designed, and the relevant research data were obtained. Studies show that virtual reality-based preventive medical devices can improve the efficiency of pressure ulcer treatment in hospitals by about 12%. Pressure ulcers have different incidences among people of different ages. The probability is much higher than that of adolescents. Foam dressing is very effective in preventing pressure ulcers. The probability of pressure ulcers after using foam dressing is about 35% lower than that when it is not used.

Transmission of a Novel Imprinting Center Deletion Associated With Prader-Willi Syndrome Through Three Generations of a Chinese Family: Case Presentation, Differential Diagnosis, and a Lesson Worth Thinking About.

Prader-Willi syndrome (PWS) is a complex genetic syndrome caused by the loss of function of genes in 15q11-q13 that are subject to regulation by genomic imprinting and expressed from the paternal allele only. The main clinical features of PWS patients are hypotonia during the neonatal and infantile stages, accompanied by delayed neuropsychomotor development, hyperphagia, obesity, hypogonadism, short stature, small hands and feet, mental disabilities, and behavioral problems. However, PWS has a clinical overlap with other disorders, especially those with other gene variations or chromosomal imbalances but sharing part of the similar clinical manifestations with PWS, which are sometimes referred to as Prader-Willi syndrome-like (PWS-like) disorders. Furthermore, it is worth mentioning that significant obesity as a consequence of hyperphagia in PWS usually develops between the ages of 1 and 6 years, which makes early diagnosis difficult. Thus, PWS is often not clinically recognized in infants and, on the other hand, may be wrongly suspected in obese and intellectually disabled patients. Therefore, an accurate investigation is necessary to differentiate classical PWS from PWS-like phenotypes, which is imperative for further treatment. For PWS, it is usually sporadic, and very rare family history and affected siblings have been described. Here, we report the clinical and molecular findings in a three-generation family with a novel 550-kb microdeletion affecting the chromosome 15 imprinting center (IC). Overall, the present study finds that the symptoms of our patient are somewhat different from those of typical PWS cases diagnosed and given treatment in our hospital. The familial occurrence and clinical features were challenging to our diagnostic strategy. The microdeletion included a region within the complex small nuclear ribonucleoprotein polypeptide protein N (SNRPN) gene locus encompassing the PWS IC and was identified by using a variety of techniques. Haplotype studies suggest that the IC microdeletion was vertically transmitted from an unaffected paternal grandmother to an unaffected father and then caused PWS in two sibling grandchildren when the IC microdeletion was inherited paternally. Based on the results of our study, preimplantation genetic diagnosis (PGD) was applied successfully to exclude imprinting deficiency in preimplantation embryos before transfer into the mother's uterus. Our study may be especially instructive regarding accurate diagnosis, differential diagnosis, genetic counseling, and PGD for familial PWS patients.