Maturity-onset diabetes of the young type 9 or latent autoimmune diabetes in adults:A case report and review of literature

BACKGROUND Maturity-onset diabetes of the young(MODY)is a monogenic genetic disease often clinically misdiagnosed as type 1 or type 2 diabetes.MODY type 9(MODY9)is a rare subtype caused by mutations in the PAX4 gene.Currently,there are limited reports on PAX4-MODY,and its clinical characteristics and treatments are still unclear.In this report,we described a Chinese patient with high autoimmune antibodies,hyperglycemia and a site mutation in the PAX4 gene.CASE SUMMARY A 42-year-old obese woman suffered diabetes ketoacidosis after consuming substantial amounts of beverages.She had never had diabetes before,and no one in her family had it.However,her autoantibody tested positive,and she managed her blood glucose within the normal range for 6 mo through lifestyle interventions.Later,her blood glucose gradually increased.Next-generation sequencing and Sanger sequencing were performed on her family.The results revealed that she and her mother had a heterozygous mutation in the PAX4 gene(c.314G>A,p.R105H),but her daughter did not.The patient is currently taking liraglutide(1.8 mg/d),and her blood glucose levels are under control.Previous cases were retrieved from PubMed to investigate the relationship between PAX4 gene mutations and diabetes.CONCLUSION We reported the first case of a PAX4 gene heterozygous mutation site(c.314G>A,p.R105H),which does not appear pathogenic to MODY9 but may facilitate the progression of latent autoimmune diabetes in adults.

Novel gene mutation in maturity-onset diabetes of the young:A case report

BACKGROUND Maturity-onset diabetes of the young(MODY)is the most common monogenic type of diabetes.Recently,14 gene mutations have been found to be associated with MODY.In addition,the KLF11 gene mutation is the pathogenic gene of MODY7.To date,the clinical and functional characteristics of the novel KLF11mutation c.G31A have not yet been reported.CASE SUMMARY We report of a 30-year-old male patient with a one-year history of nonketosisprone diabetes and a 3-generation family history of diabetes.The patient was found to carry a KLF11 gene mutation.Therefore,the clinical data of family members were collected and investigated.A total of four members of the family were found to have heterozygous mutations in the KLF11 gene c.G31A,which resulted in a change in the corresponding amino acid p.D11N.Three patients had diabetes mellitus,and one patient had impaired glucose tolerance.CONCLUSION The heterozygous mutation of the KLF11 gene c.G31A(p.D11N)is a new mutation site of MODY7.Subsequently,the main treatment included dietary interventions and oral drugs.

Maturity-onset diabetes of the young type 10 caused by an Ala2Thr mutation of INS:A case report

Maturity-onset diabetes of the young 10 caused by the c.4G>A (p.Ala2Thr)mutation is extremely rare, with only two reported studies to date. Herein, wereport another case that differs from previous cases in phenotype.CASE SUMMARYThe proband developed diabetes at the age of 27 years, despite having a normalbody mass index (BMI). She exhibited partial impairment of islet function, testedpositive for islet antibodies, and required high doses of insulin. Her sister alsocarried the c.4G>A (p.Ala2Thr) mutation, and their mother was stronglysuspected to carry the mutated gene. Her sister developed diabetes around 40years of age and required high doses of insulin, while the mother was diagnosedin her 20s and was managed with oral hypoglycemic agents;neither of them wereobese.CONCLUSION p.Ala2Thr mutation carriers often experience relatively later onset and normalBMI. Treatment regimens vary between individuals.

Novel HNF1A gene mutation in maturity-onset diabetes of the young:A case report

BACKGROUND Maturity-onset diabetes of the young 3(MODY3),caused by mutations in the HNF1A gene,is the most common subtype of MODY.The diagnosis of MODY3 is critical because a low dose of sulfonylurea agents can achieve glucose control.CASE SUMMARY We describe a patient with MODY3 involving a novel splicing mutation,in whom low-dose gliclazide was sufficient to control clinically significant hyperglycemia.Sanger sequencing identified a splicing HNF1A mutation in 12q24 NM_000545.5 Intron5 c.1108-1G>A.Glycemic control has been maintained without insulin therapy for 28 mo after the diagnosis of diabetes.CONCLUSION This case report highlights a novel HNF1A gene mutation in MODY3 that is responsive to sulfonylurea therapy.

Corticosteroid-induced bradycardia in multiple sclerosis and maturity-onset diabetes of the young due to hepatocyte nuclear factor 4-alpha mutation:A case report

BACKGROUND Intravenous steroid pulse therapy is the treatment of choice for acute exacerbation of multiple sclerosis(MS).Although steroid administration is generally welltolerated,cases of cardiac arrhythmia have been reported.Herein,we describe a young woman who developed marked sinus bradycardia and T-wave abnormalities after corticosteroid administration.We also present plausible explanations for the abnormalities observed in this patient.CASE SUMMARY An 18-year-old woman experienced vertiginous dizziness and binocular diplopia 1 wk prior to admission.Neurological examination revealed left internuclear ophthalmoplegia with left peripheral-type facial palsy.The initial laboratory results were consistent with those of type 2 diabetes.Brain magnetic resonance imaging revealed multifocal,non-enhancing,symptomatic lesions and multiple enhancing lesions.She was diagnosed with MS and maturity-onset diabetes of the young.Intravenous methylprednisolone was administered.On day 5 after methylprednisolone infusion,marked bradycardia with T-wave abnormalities were observed.Genetic evaluation to elucidate the underlying conditions revealed a hepatocyte nuclear factor 4-alpha(HNF4A)gene mutation.Steroid treatment was discontinued under suspicion of corticosteroid-induced bradycardia.Her electrocardiogram changes returned to normal without complications two days after steroid discontinuation.CONCLUSION Corticosteroid-induced bradycardia may have a significant clinical impact,especially in patients with comorbidities,such as HNF4A mutations.

The Young Star Bridging the World to China——Exclusive Interview with World Youth Leadership Foundation Chairman Franco Ng

My f irst impression of Franco Ng came during his visit to our Beijing offices.At that time,he was in Beijing as a guest with the National Bank of Canada speaking about his educational experiences growing up in Canada,while promoting“The Win”,a Global Youth Venture Competition he established with the World Youth Leadership Foundation this year.

As a Cultural and Spiritual Homeland:Pai Hsien-yung and His Kunqu Peony Pavilion:The Young Lovers’Version

As a Cultural and Spiritual Homeland,Pai Hsien-yung and His Kunqu Peony Pavilion:The Young Lovers’Version,the new version of The Jade Hairpin,how to be the most aesthetic version,cross-border version and young version,as a sustainable development model.

The Young Cyber-consumers

Children are keen Internet shoppers with more than half having bought something online,research has shown. Around 53 per cent of children aged between 7 and 16 said they had purchased something over the Internet,10 per cent more than in 2004,according to Halifax. Boys were more likely to be Internet shoppers than girls,with 60 per cent of boys saying they had bought items online,compared with just 46 per cent of girls.

Prevalence of maturity-onset diabetes of the young in phenotypic type 2 diabetes in young adults:a nationwide,multi-center,cross-sectional survey in China

Background:Maturity-onset diabetes of the young(MODY)is the most common monogenic diabetes.The aim of this study was to assess the prevalence of MODY in phenotypic type 2 diabetes(T2DM)among Chinese young adults.Methods:From April 2015 to October 2017,this cross-sectional study involved 2429 consecutive patients from 46 hospitals in China,newly diagnosed between 15 years and 45 years,with T2DM phenotype and negative for standardized glutamic acid decarboxylase antibody at the core laboratory.Sequencing using a custom monogenic diabetes gene panel was performed,and variants of 14 MODY genes were interpreted as per current guidelines.Results:The survey determined 18 patients having genetic variants causing MODY(6 HNF1A,5 GCK,3 HNF4A,2 INS,1 PDX1,and 1 PAX4).The prevalence of MODY was 0.74%(95%confidence interval[CI]:0.40-1.08%).The clinical characteristics of MODY patients were not specific,72.2%(13/18)of them were diagnosed after 35 years,47.1%(8/17)had metabolic syndrome,and only 38.9%(7/18)had a family history of diabetes.No significant difference in manifestations except for hemoglobin A1c levels was found between MODY and non-MODY patients.Conclusion:The prevalence of MODY in young adults with phenotypic T2DM was 0.74%,among which HNF1A-,GCK-,and HNF4A-MODY were the most common subtypes.Clinical features played a limited role in the recognition of MODY.

How Resilient Is the Family? An Empirical Study of Family Care for the Young and the Elderly

This study explores the strategies Chinese families employ to navigate substantial caregiving challenges in the context of demographic changes characterized by low birth rates and an aging populace, alongside a dearth of public and commercial caring resources. It delves into familial intergenerational cooperation, utilizing various resources such as connections, norms, and emotions to develop resilience that withstands external pressures. The research acknowledges the positive role of family resilience in safeguarding vulnerable members and maintaining social stability. However, it also highlights the fact that family resilience has its limits and does not have unlimited sustainability. Sustainable family resilience can be bolstered by redefining the distribution of duties and resources among the government, the community, and families for the care of the young and the elderly. This involves creating a multifaceted welfare system anchored by government backing that places families at its center and by improving the commercial provision of care services. This facilitates the positive self-generation and reproduction of caring resources within the familial framework.

Analysis of an adult diabetes mellitus caused by a rare mutation of the gene:A case report

BACKGROUND This study presents the clinical and genetic mutation characteristics of an unusual case of adult-onset diabetes mellitus occurring in adolescence,featuring a unique mutation in the peroxisome proliferator-activated receptor gamma(PPARG)gene.Data Access Statement:Research data supporting this publication are available from the NN repository at www.NNN.org/download/.CASE SUMMARY The methodology employed entailed meticulous collection of comprehensive clinical data from the probands and their respective family members.Additionally,high-throughput sequencing was conducted to analyze the PPARG genes of the patient,her siblings,and their offspring.The results of this investigation revealed that the patient initially exhibited elevated blood glucose levels during pregnancy,accompanied by insulin resistance and hypertriglyceridemia.Furthermore,these strains displayed increased susceptibility to diabetic kidney disease without any discernible aggregation patterns.The results from the gene detection process demonstrated a heterozygous mutation of guanine(G)at position 284 in the coding region of exon 2 of PPARG,which replaced the base adenine(A)(exon2c.284A>Gp.Tyr95Cys).This missense mutation resulted in the substitution of tyrosine with cysteine at the 95th position of the translated protein.Notably,both of her siblings harbored a nucleotide heterozygous variation at the same site,and both were diagnosed with diabetes.CONCLUSION The PPARG gene mutation,particularly the p.Tyr95Cys mutation,may represent a newly identified subtype of maturity-onset diabetes of the young.This subtype is characterized by insulin resistance and lipid metabolism disorders.

A Family of GCK-MODY, About 02 Cases and Review of the Literature

Positive diagnosis of diabetes is currently easy, but typing diagnosis of diabetes still remains a challenge for every clinician. It is currently accepted that types of diabetes apart from T1D and T2D can expand and include several forms of diabetes mellitus;From gestational diabetes, to all forms of secondary diabetes mellitus due to medications, intercurrent disease but also infections, and finally monogenic diabetes, whose diagnosis is not always easy to establish. The aim is to reveal the difficulties that clinicians may face in the process of etiological diagnosis regarding the suspicion of this type of monogenic diabetes, through the study of 2 cases, in which MODY type diabetes was suspected. Today we recognize 17 different genetic mutations that can all lead to MODY diabetes, the most common mutation of which is GCK coding for the glucokinase, the real sensor of pancreatic Beta-cell. The truly stable glycemic profile, with an A1C ranging between 7% and 7.5%, confirmed with a TIR always above 70% and a good MAGE, but also the rarity of degenerative complications and pharmacological therapeutic abstention which can last for years, these would be the most striking clinical characteristics of a GCK MODY.

Popular With the Young

Chopin continues to exert a strong influence upon young piano learners in China Located along the West Third Ring Road of Beijing, the piano school of the Jiang Jie Culture and Arts School, lone of the most popular music schools for children in the city, has never been

The Young Women of TEDA

IN his report to the United States State Department after he returned from a survey of the city of Tianjin, Dr. George Lee, the American Trade Councillor to China, said, "The Tianjin Economic Development Area (TEDA) has probably the most suitable investment environment in China. My deepest impression of TEDA is that the administrative officers are young and enlightened. Their slogan is: ’The investors are the sovereign and the project is the lifeline.’ For Americans interested in investing in China, we suggest that they pay a visit to TEDA."

Monogenic diabetes in children:An underdiagnosed and poorly managed clinical dilemma

Monogenic diabetes,constituting 1%-2%of global diabetes cases,arises from single gene defects with distinctive inheritance patterns.Despite over 50 associated genetic disorders,accurate diagnoses and management of monogenic diabetes remain inadequate,underscoring insufficient clinician awareness.The disease spectrum encompasses maturity-onset diabetes of the young(MODY),characterized by distinct genetic mutations affecting insulin secretion,and neonatal diabetes mellitus(NDM)-a heterogeneous group of severe hyperglycemic disorders in infants.Mitochondrial diabetes,autoimmune monogenic diabetes,genetic insulin resistance and lipodystrophy syndromes further diversify the monogenic diabetes landscape.A tailored approach based on phenotypic and biochemical factors to identify candidates for genetic screening is recommended for suspected cases of MODY.NDM diagnosis warrants immediate molecular genetic testing for infants under six months.Identifying these genetic defects presents a unique opportunity for precision medicine.Ongoing research aimed to develop cost-effective genetic testing methods and gene-based therapy can facilitate appropriate identification and optimize clinical outcomes.Identification and study of new genes offer a valuable opportunity to gain deeper insights into pancreatic cell biology and the pathogenic mechanisms underlying common forms of diabetes.The clinical review published in the recent issue of World Journal of Diabetes is such an attempt to fill-in our knowledge gap about this enigmatic disease.

Management of monogenic diabetes in pregnancy:A narrative review

Pregnancy in women with monogenic diabetes is potentially complex,with significant implications for both maternal and fetal health.Among these,maturity-onset diabetes of the young(MODY)stands out as a prevalent monogenic diabetes subtype frequently encountered in clinical practice.Each subtype of MODY requires a distinct approach tailored to the pregnancy,diverging from management strategies in non-pregnant individuals.Glucokinase MODY(GCK-MODY)typically does not require treatment outside of pregnancy,but special considerations arise when a woman with GCK-MODY becomes pregnant.The glycemic targets in GCK-MODY pregnancies are not exclusively dictated by the maternal/paternal MODY genotype but are also influenced by the genotype of the developing fetus.During pregnancy,the choice between sulfonylurea or insulin for treating hepatocyte nuclear factor 1-alpha(HNF1A)-MODY and HNF4A-MODY depends on the mother’s specific circumstances and the available expertise.Management of other rarer MODY subtypes is individu-alized,with decisions made on a case-by-case basis.Therefore,a collaborative approach involving expert diabetes and obstetric teams is crucial for the compre-hensive management of MODY pregnancies.

Assessment of pathogenicity and functional characterization of APPL1 gene mutations in diabetic patients

BACKGROUND Adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 1(APPL1)plays a crucial role in regulating insulin signaling and glucose metabolism.Mutations in the APPL1 gene have been associated with the development of maturity-onset diabetes of the young type 14(MODY14).Currently,only two mutations[c.1655T>A(p.Leu552*)and c.281G>A p.(Asp94Asn)]have been identified in association with this disease.Given the limited understanding of MODY14,it is imperative to identify additional cases and carry out comprehensive research on MODY14 and APPL1 mutations.AIM To assess the pathogenicity of APPL1 gene mutations in diabetic patients and to characterize the functional role of the APPL1 domain.METHODS Patients exhibiting clinical signs and a medical history suggestive of MODY were screened for the study.Whole exome sequencing was performed on the patients as well as their family members.The pathogenicity of the identified APPL1 variants was predicted on the basis of bioinformatics analysis.In addition,the pathogenicity of the novel APPL1 variant was preliminarily evaluated through in vitro functional experiments.Finally,the impact of these variants on APPL1 protein expression and the insulin pathway were assessed,and the potential mechanism underlying the interaction between the APPL1 protein and the insulin receptor was further explored.RESULTS A total of five novel mutations were identified,including four missense mutations(Asp632Tyr,Arg633His,Arg532Gln,and Ile642Met)and one intronic mutation(1153-16A>T).Pathogenicity prediction analysis revealed that the Arg532Gln was pathogenic across all predictions.The Asp632Tyr and Arg633His variants also had pathogenicity based on MutationTaster.In addition,multiple alignment of amino acid sequences showed that the Arg532Gln,Asp632Tyr,and Arg633His variants were conserved across different species.Moreover,in in vitro functional experiments,both the c.1894G>T(at Asp632Tyr)and c.1595G>A(at Arg532Gln)mutations were found to downregulate the expression of APPL1 on both protein and mRNA levels,indicating their pathogenic nature.Therefore,based on the patient’s clinical and family history,combined with the results from bioinformatics analysis and functional experiment,the c.1894G>T(at Asp632Tyr)and c.1595G>A(at Arg532Gln)mutations were classified as pathogenic mutations.Importantly,all these mutations were located within the phosphotyrosinebinding domain of APPL1,which plays a critical role in the insulin sensitization effect.CONCLUSION This study provided new insights into the pathogenicity of APPL1 gene mutations in diabetes and revealed a potential target for the diagnosis and treatment of the disease.

The Inevitable Fall of the Dreamers:on the Comparison between the Syrian in Salome and Zhou Chong in Thunderstorm

As a world-renowned masterpiece of Irish outstanding playwright Oscar Wilde,the soul of the aestheticism movement,Salome,which adapted from the story of the daughter of Herodias in New Testament,has been continuing its glamorous and unique charm not only in the field of literature but in other artistic field.At present,academic studies about Salome has been developing many different interpretation from various angles,such as aestheticism,feminist studies,and other very insightful theories.And Thunderstorm written by Chinese playwright Cao Yu has the same theme as Salome-the inevitable death of dreamers,though the young Syrian and Zhou Chong are in different society systems.This paper would go deeper on the topic of the fall of these two sup⁃porting characters.

Genetic perspectives on childhood monogenic diabetes:Diagnosis,management,and future directions

Monogenic diabetes is caused by one or even more genetic variations, which maybe uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1 to 5% of children, and early detection and geneticallyfocused treatment of neonatal diabetes and maturity-onset diabetes of theyoung can significantly improve long-term health and well-being. The etiology ofmonogenic diabetes in childhood is primarily attributed to genetic variationsaffecting the regulatory genes responsible for beta-cell activity. In rare instances,mutations leading to severe insulin resistance can also result in the developmentof diabetes. Individuals diagnosed with specific types of monogenic diabetes,which are commonly found, can transition from insulin therapy to sulfonylureas,provided they maintain consistent regulation of their blood glucose levels.Scientists have successfully devised materials and methodologies to distinguishindividuals with type 1 or 2 diabetes from those more prone to monogenicdiabetes. Genetic screening with appropriate findings and interpretations isessential to establish a prognosis and to guide the choice of therapies andmanagement of these interrelated ailments. This review aims to design a comprehensiveliterature summarizing genetic insights into monogenetic diabetes inchildren and adolescents as well as summarizing their diagnosis and management.

A Case Report of MODY_(3)Combined with Intestinal Neuroendocrine Tumor

Maturity-onset diabetes of the young 3(MODY_(3))is an autosomal dominant monogenic diabetes mellitus characterized by defective p-cell function and non-insulin-dependent early-onset diabetes mellitus.The facts that patients with MODY_(3) are often misdiagnosed as type 1 and type 2 diabetes mellitus and genetic diagnosis is expensive,make its diagnosis very challenging.In this study,we reported a case of MODY_(3),which was verified to be caused by a mutation in hepatocyte nuclear factor 1αgene(c.598C>X p.Arg200Trp).In addition,the patient had a neuroendocrine tumor simultaneously,and a KMT2D gene mutation(c.5587C>G,p.Prol863Ala)might be associated with this leson.