Mental retardation,seizures and language delay caused by new SETD1B mutations:Three case reports

BACKGROUND The SETD1B gene is instrumental in human intelligence and nerve development.Mutations in the SETD1B gene have been linked in recent studies to neurodevelopmental disorders,seizures,and language delay.CASE SUMMARY This study aimed to analyze the clinical manifestations and treatment of three patients suffering from mental retardation,epilepsy,and language delay resulting from a new mutation in the SETD1B gene.Three individuals with these symptoms were selected,and their clinical symptoms,gene test results,and treatment were analyzed.This article discusses the impact of the SETD1B gene mutation on patients and outlines the treatment approach.Among the three patients(two females and one male,aged 8,4,and 1,respectively),all exhibited psychomotor retardation,attention deficit,and hyperactivity disorder,and two had epilepsy.Antiepileptic treatment with sodium tripolyvalproate halted the seizures in the affected child,although mental development remained somewhat delayed.Whole exome sequencing revealed new mutations in the SETD1B gene for all patients,specifically with c.5473C>T(p.Arg1825trp),c.4120C>T(p.Gln1374*,593),c.14_15insC(p.His5Hisfs*33).CONCLUSION Possessing the SETD1B gene mutation may cause mental retardation accompanied by seizures and language delay.Although the exact mechanism is not fully understood,interventions such as drug therapy,rehabilitation training,and family support can assist patients in managing their symptoms and enhancing their quality of life.Furthermore,genetic testing supplies healthcare providers with more precise diagnostic and therapeutic guidance,informs families about genetic disease risks,and contributes to understanding disease pathogenesis and drug research and development.

Analysis of the Phenotype and the Restriction Enzyme Mapping Level of Mutations Induced by the New Mutagen Glycidyl Methacrylate

Glycidyl methaerylate (GMA) is a recently recognized chemical mutagen. In order to explore the mutagenicity and mutagenic process of GMA, plasmid pBR322 was used for in vitro binding, mutant screening, and restriction enzyme mapping. The binding between GMA and DNA in vitro has been verified by means of a spectrophotometric method. When pBR322 and GMAbound pBR322 were used to transform Eschenchia coli HB101, the following results were obtained: (1) The transformation efficiency of GMA-bound pBR322 was much lower than that of pBR322 alone. (2) GMA-bound pBR322 induced phenotype changes in competent cells (i.e., tetracycline-resistance inactivation or ampicillin-resistance inactivation). There were two mutants of pBR322, Ap~RTc~S and Ap~STc~R, in the transformants and a deductive mutant Ap~STc~S in the nontranstormants. (3) All of the selected mutants were stable and heritable. (4) When restriction enzyme maps were used to analyze the mutant Ap~RTc~S, four of seven maps were changed. some sites were shifted to other resistant gene regions, for example, sites of Bgll, EcoRl, Ilindlll. Hinclll, etc., and there was a new recognition site for Hindi (252). We did not observe any DNA fragment insertion or deletion on any maps. Our results suggest that when GMA is covalently linked to the plasmid DNA, it gives rise to a premutagenic lesion of DNA that is converted in vivo into a point mutation. (C)1990 Academic Press, Inc.

A novel mutation in POU3F4 in a Chinese family with X-linked non-syndromic hearing loss

Objective： Based on the clinical manifestations of a hearing loss patient, the POU3F4 gene was tested for diagnosis of etiology. Methods： A comprehensive physical examination was performed on the proband to exclude abnormalities of other organs, and detailed audi- ological testing and temporal bone CT scan were also performed. Genomic DNA was extracted using the proband＇s peripheral blood leukocytes. Polymerase chain reactions （PCR） were performed in the coding sequence of the POU3F4 gene. Direct DNA sequencing was subsequently applied to screen the entire coding region of the POU3F4 gene. Results： The proband had severe sensorineural hearing loss. Temporal CT showed bilateral cochlear incomplete partition, vestibule dysplasia, internal auditory canal fundus expansion, and cochlear interlink with the internal auditory canal fundus. A novel mutation （c.530C 〉 A （p.S 177X）） in the POU3F4 gene was found in this patient, creating an new stop codon and was predicted to result in a truncated protein lacking normal POU3F4 transcription factor function. Conclusion： Through analysis of the POU3F4 gene and clinical manifestations in the patient, we conclude that a novel mutation may have resulted in a premature stop codon, contributing to the mutation of POU3F4 gene.

Emergence of lesions outside of the basal ganglia and irreversible damage to the basal ganglia with severeβ-ketothiolase deficiency:A case report

BACKGROUNDβ-ketothiolase deficiency(β-KTD)is an inherited disease,and insufficient attention has been paid to imageology due to its lower morbidity.Therefore,few lesions outside the basal ganglia have been found before,and the persistent pathological changes have rarely been reported.CASE SUMMARY A 10-mo-old Chinese female patient with a free previous medical history but with poor physical and athletic development had received the haemophilus influenzae vaccine and then developed a low fever 2 d prior.She was initially diagnosed with severe brain injury,central respiratory failure,metabolic acidosis complicated with respiratory alkalosis,hyper-IgE,etc.With further examination,a definite diagnosis ofβ-KTD was made.Symptomatic treatment was adopted.Ten days later,the dyspnea was improved evidently and the ventilator was removed,but there were still obvious abnormalities on magnetic resonance imaging(MRI).The lesions mainly invaded the corpus striatum but were not limited to the basal ganglia.Then,the patient’s disease improved and discharged approximately 1 mo later,and the abnormal lesions on MRI had partially improved.However,for about 1 year,the residual irreversible lesions were observed on MRI,the mental and physical development of the patient was obviously regressive,and extra rehabilitation training was needed.CONCLUSION The case highlights the critical importance of one view that the range of lesions in some patients may be more extensive than previously thought in someβ-KTD patients.In addition to biochemical tests,genetic tests and magnetic resonance imaging are not only conducive to quickly diagnosingβ-KTD but also to partially evaluating the short-and long-term outcomes.Moreover,more attention should be paid to the two mutations(c.478 C>G;c.951 C>T)that may be associated with severeβ-KTD.

突变观与渐变观的较量——《新青年》的进化论思想实践及历史影响

在进化论思想已经获得广泛传播的条件下,《新青年》转向了进化论思想的实践,推动反封建的思想革命。在重大历史转折关头,新青年一派坚持进化论思想中以渐变为前提的突变观念。这表现为他们观念中的新旧思想对立和中西文化发展水平的时代差异,并试图以西方文明来革新中国传统文化。进化论思想中的渐变和突变观念,分别给激进主义和保守主义提供了思想工具。在实践中存在一种时机错位的现象,即特定时期的思想论争,其思维模式在事过境迁后它的应有有效性会发生逆转,好像历史又回到了原来的起点上;但激进或保守的历史作用,最终要接受历史的裁定。