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1.
Protein & Cell ; (12): 52-68, 2024.
Article in English | WPRIM | ID: wpr-1010786

ABSTRACT

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.


Subject(s)
Female , Animals , Mice , Humans , Child, Preschool , Intellectual Disability/genetics , Heart Defects, Congenital/genetics , Facies , Cleft Palate , Muscle Hypotonia
2.
Chinese Journal of Medical Genetics ; (6): 86-91, 2024.
Article in Chinese | WPRIM | ID: wpr-1009358

ABSTRACT

OBJECTIVE@#To explore the clinical characteristics and genetic variant in a child with neurodevelopmental disorders (NDDs).@*METHODS@#Clinical data of a child who had presented at Xiaogan Hospital Affiliated to Wuhan University of Science and Technology in December 2020 due to intermittent convulsions for over a year were retrospectively analyzed. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. "HNRNPU gene", "epilepsy", "epileptic encephalopathy", "hereditary epilepsy", "neurodevelopmental disorder", "neurodevelopmental syndrome", "HNRNPU", and "NDDs" were used as the key words to search the CNKI, Wanfang and PubMed databases dated from January 1, 1994 to February 10, 2022.@*RESULTS@#The patient was a 2-year-old boy who had developed seizure at the age of 5 months. His clinical features had included abnormal appearance, recurrent seizures, and low developmental quotients of each functional area as evaluated by the Gesell scale. The child was given sodium valproate for the antiepileptic treatment and rehabilitation training. He had become seizure-free within half a year of follow-up, but his intelligence and motor development did not improve significantly. Genetic testing revealed that he has harbored a heterozygous c.1720_1722delCTT (p.Lys574del) variant of the HNRNPU gene, which was not found in either of his parents. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PS2+PM2_Supporting+PM4). A total of 13 articles were retrieved, and the types of HNRNPU gene mutations have included splice site mutation, nonsense mutation, missense mutation, in-frame deletion, gene duplication, frameshifting mutation, and multiple exon deletion. The main clinical manifestations have included mental retardation, language delay, global developmental delay, epilepsy, craniofacial deformity, mental and behavioral abnormalities.@*CONCLUSION@#The c.1720_1722delCTT variant of the HNRNPU gene probably underlay the NDDs in this child. Above finding has enriched the mutational spectrum of the HNRNPU gene.


Subject(s)
Male , Child , Humans , Infant , Child, Preschool , Retrospective Studies , Neurodevelopmental Disorders/genetics , Intellectual Disability , Mutation , Seizures , Epilepsy, Generalized
3.
Chinese Journal of Medical Genetics ; (6): 67-74, 2024.
Article in Chinese | WPRIM | ID: wpr-1009355

ABSTRACT

OBJECTIVE@#To explore the genetic basis of two children with unexplained psychomotor developmental delay and facial dysmorphisms suggestive of Coffin-Siris syndrome (CSS).@*METHODS@#A boy and a girl suspected for CSS at the 980th Hospital of the People's Liberation Army Joint Service Support Force respectively in July 2019 and January 2021, and seven members from their families, were selected as the study subjects. Clinical data and family history of the children were collected, and detailed physical examination was carried out, in addition with laboratory and related auxiliary examinations. Potential variants and copy number variations (CNVs) were detected by whole exome sequencing (WES) and copy number variation sequencing (CNV-seq).@*RESULTS@#Child 1, an 8-month-old female, had featured microcephaly, atrial septal defect, curving of fifth finger/toe, and low limb muscle tone. Child 2 was a 2.5-year-old male with language delay, social impairment, dense hair but no curving of the fifth fingers. Genetic testing revealed that child 1 had loss of heterozygosity for exons 8 to 21 of the ARID1B gene, which was unreported previously. Family verification showed that both of her parents were of the wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and American Society of Molecular Pathology (AMP), the variant was rated as pathogenic (PVS1+PS2+PM2-supporting). Child 2 was found to harbor a heterozygous c.4263-6 (IVS17) T>G variant of the ARID1B gene. Transcriptome sequencing confirmed that the variant can affect the normal splicing, resulting in retention of a 5 bp sequence in intron 17. Family verification showed that both of his parents were of the wild type. Based on the guidelines from the ACMG, the variant was rated as pathogenic (PS2+PM2-supporting+PP3+PS3).@*CONCLUSION@#WES and RNA-seq have confirmed the diagnosis of CSS in both children. Discovery of the novel variants has expanded the spectrum of pathogenic mutations underlying CSS, and provided a basis for the genetic counseling.


Subject(s)
Child, Preschool , Female , Humans , Infant , Male , Abnormalities, Multiple/diagnosis , DNA Copy Number Variations , DNA-Binding Proteins/genetics , Intellectual Disability/diagnosis , Micrognathism/genetics , Mutation , Transcription Factors/genetics
5.
Psico USF ; 28(4): 811-824, Oct.-Dec. 2023. tab
Article in English | LILACS, INDEXPSI | ID: biblio-1529169

ABSTRACT

This study had as general objective to characterize and associate social skills, behavior problems, and academic competence of students with intellectual disabilities in school inclusion and; as specific objectives to verify predictive values for social skills and differences between groups diagnosed with intellectual disability and other associated diagnoses. This was a quantitative, cross-sectional, descriptive, correlational, predictive, and comparative study. Forty-four students with intellectual disability participated (11 of them presented other associated diagnoses), who were evaluated by 42 guardians and 34 teachers. The instruments used were Social Skills Rating System (SSRS-BR) and the Parental Educative Social Skills Interview Script (RE-HSE-P). The evaluation from guardians and teachers were different. Social skills were negatively associated with behavior problems and positively associated with academic competence; behavior problems and diagnosis were negative predictors to social skills. There were significant differences in the groups. The results highlight the importance of intervention programs to develop social skills.(AU)


O estudo teve como objetivo geral caracterizar e associar habilidades sociais, problemas de comportamento e competência acadêmica de alunos com deficiência intelectual em inclusão educacional e; como objetivos específicos verificar valores preditivos para habilidades sociais e diferenças entre grupos com diagnóstico de deficiência intelectual somente e com outros diagnósticos associados. Trata-se de um estudo quantitativo, transversal, descritivo, correlacional, preditivo e comparativo. Participaram 44 alunos com deficiência (11 apresentavam outros diagnósticos associados), que foram avaliados por 42 responsáveis e 34 professoras. Os instrumentos utilizados foram Social Skills Rating System (SSRS-BR) e Roteiro de Entrevista de Habilidades Sociais Educativas Parentais (RE-HSE-P). A avaliação de responsáveis e professores foi diferente. Habilidades sociais foram negativamente associadas aos problemas de comportamento e positivamente associadas a competência acadêmica; problemas de comportamento e diagnósticos associados foram preditores negativos de habilidades sociais. Houve diferença significativa entre grupos. Resultados evidenciam a importância de programas para promoção de habilidades sociais.(AU)


Este estudio tuvo como objetivo general caracterizar y asociar las habilidades sociales, los problemas de conducta y la competencia académica de estudiantes con discapacidad intelectual en la inclusión escolar; y como objetivos específicos verificar los valores predictivos de las habilidades sociales y las diferencias entre grupos diagnosticados con discapacidad intelectual y otros diagnósticos asociados. Se trató de un estudio cuantitativo, transversal, descriptivo, correlacional, predictivo y comparativo. Participaron 44 estudiantes con discapacidad intelectual (11 de ellos presentaban otros diagnósticos asociados), quienes fueron evaluados por 42 tutores y 34 docentes. Los instrumentos utilizados fueron el Sistema de Evaluación de Habilidades Sociales (SSRS-BR) y el Guion de Entrevista de Habilidades Sociales para Educación de los Padres (RE-HSE-P). Las evaluaciones de los tutores y docentes fueron diferentes. Las habilidades sociales se asociaron negativamente con problemas de conducta y positivamente con la competencia académica; los problemas de conducta y el diagnóstico fueron predictores negativos de las habilidades sociales. Hubo diferencias significativas entre los grupos. Los resultados destacan la importancia de los programas de intervención para desarrollar habilidades sociales con la población estudiada.(AU)


Subject(s)
Humans , Male , Female , Child , Adult , Social Skills , Problem Behavior/psychology , Academic Performance/psychology , Intellectual Disability/psychology , Mainstreaming, Education , Cross-Sectional Studies , Interviews as Topic , Predictive Value of Tests , Data Interpretation, Statistical , Correlation of Data , Sociodemographic Factors
6.
Rev. Hosp. Ital. B. Aires (2004) ; 43(3): 143-146, sept. 2023. ilus, tab
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1517927

ABSTRACT

Se presenta un niño de 6 años con antecedente de retraso del lenguaje que llevó a sus padres a realizar múltiples consultas. En un primer momento, su cuadro fue interpretado como parte de un retraso global del desarrollo. Posteriormente, el paciente presentó convulsiones y episodios de descompensación metabólica, comenzando desde entonces su seguimiento por los Servicios de neurología, genética y metabolismo. Finalmente, tras varios estudios complementarios, por medio de un exoma trío se arribó al diagnóstico de síndrome de microduplicación del cromosoma 7q11.23, lo que justifica tanto el retraso global de desarrollo del paciente como su clínica neurológica. (AU)


A six-year-old boy presents with a history of language delay that led his parents to make multiple consultations. At first, we interpreted his condition as part of a global developmental delay. Subsequently, the patient presented seizures and episodes of metabolic decompensation, and since then, he had to be followed up by neurology, genetics, and metabolism services. Finally, after several complementary studies, following a trio exome analysis, we diagnosed chromosome 7q11.23 microduplication syndrome, which explains his global developmental delay and neurological symptoms. (AU)


Subject(s)
Humans , Male , Child , Chromosomes, Human, Pair 7/genetics , Developmental Disabilities/genetics , Williams Syndrome/genetics , Chromosome Duplication , Language Development Disorders/genetics , Intellectual Disability/genetics , Developmental Disabilities/diagnosis , Developmental Disabilities/metabolism , Genetic Testing , Williams Syndrome/diagnosis , Williams Syndrome/metabolism , Language Development Disorders/diagnosis , Intellectual Disability/diagnosis , Intellectual Disability/metabolism
7.
Chinese Journal of Pediatrics ; (12): 1124-1128, 2023.
Article in Chinese | WPRIM | ID: wpr-1013234

ABSTRACT

Objective: To summarize the clinical characteristics of epileptic seizure associated with neurofibromatosis type 1 (NF1). Methods: From January 2017 to July 2023 at Children's Hospital Capital Institute of Pediatrics, medical records of patients with both NF1 and epileptic seizure were reviewed in this case series study. The clinical characteristics, treatment and prognosis were analyzed retrospectively. Results: A total of 15 patients(12 boys and 3 girls) were collected. Café-au-lait macules were observed in all 15 patients. There were 6 patients with neurodevelopmental disorders and the main manifestations were intellectual disability or developmental delay. The age at the first epileptic seizure was 2.5 (1.2, 5.5) years. There were various seizure types, including generalized tonic-clonic seizures in 8 patients, focal motor seizures in 6 patients, epileptic spasm in 4 patients, tonic seizures in 1 patient, absence in 1 patient, generalized myoclonic seizure in 1 patient and focal to bilateral tonic-clonic seizure in 1 patient. Among 14 patients whose brain magnetic resonance imaging results were available, there were abnormal signals in corpus callosum, basal ganglia, thalamus or cerebellum in 6 patients, dilated ventricles of different degrees in 3 patients, blurred gray and white matter boundary in 2 patients, agenesis of corpus callosum in 1 patient and no obvious abnormalities in the other patients. Among 13 epilepsy patients, 8 were seizure-free with 1 or 2 antiseizure medications(ASM), 1 with drug resistant epilepsy was seizure-free after left temporal lobectomy, and the other 4 patients who have received 2 to 9 ASM had persistent seizures. One patient with complex febrile convulsion achieved seizure freedom after oral administration of diazepam on demand. One patient had only 1 unprovoked epileptic seizure and did not have another seizure without taking any ASM. Conclusions: The first epileptic seizure in NF1 patients usually occurs in infancy and early childhood, with the main seizure type of generalized tonic-clonic seizure and focal motor seizure. Some patients have intellectual disability or developmental delay. Most epilepsy patients achieve seizure freedom with ASM.


Subject(s)
Male , Female , Humans , Child, Preschool , Child , Neurofibromatosis 1/diagnosis , Retrospective Studies , Intellectual Disability , Electroencephalography , Epilepsy/etiology , Seizures/etiology
8.
Chinese Journal of Pediatrics ; (12): 726-730, 2023.
Article in Chinese | WPRIM | ID: wpr-1013162

ABSTRACT

Objective: To discuss the clinical and genetic features of intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures (IDDBCS). Methods: The clinical and genetic records of a patient who was diagnosed with IDDBCS caused by PHF21A gene variation at Children's Hospital Capital Institute of Pediatrics in 2021 were collected retrospectively. Using " PHF21A gene" as the keyword, relevant articles were searched at CNKI, Wanfang Data and PubMed from establishment of databases to February 2023. Clinical and genetic features of IDDBCS were summarized in the combination of this case. Results: An 8 months of age boy showed overgrowth (height, weight and head circumference were all higher than the 97th percentile of children of the same age and sex) and language and motor developmental delay after birth, and gradually showed autism-like symptoms like stereotyped behavior and poor eye contact. At 8 months of age, he began to show epileptic seizures, which were in the form of a series of spastic seizures with no reaction to adrenocorticotropic hormone but a good response to vigabatrin. Physical examination showed special craniofacial appearances including a prominent high forehead, sparse eyebrows, broad nasal bridge, and downturned mouth with a tent-shaped upper lip. The patient also manifested hypotonia. Whole exome sequencing showed a de novo heterogeneous variant, PHF21A (NM_001101802.1): c.54+1G>A, and IDDBCS was diagnosed. A total of 6 articles (all English articles) were collected, involving this case and other 14 patients of IDDBCS caused by PHF21A gene variation. Clinical manifestations were intellectual disability or developmental delay (15 patients), craniofacial anomalies (15 patients), behavioral abnormalities (12 patients), seizures (9 patients), and overgrowth (8 patients). The main pathogenic variations were frameshift variations (8 patients). Conclusions: IDDBCS should be considered when patients show nervous developmental abnormalities, craniofacial anomalies, seizures and overgrowth. PHF21A gene variation detection helps to make a definite diagnosis.


Subject(s)
Male , Humans , Child , Intellectual Disability/genetics , Developmental Disabilities/genetics , Retrospective Studies , Seizures/genetics , Craniofacial Abnormalities/genetics , Histone Deacetylases/genetics
9.
Chinese Acupuncture & Moxibustion ; (12): 517-521, 2023.
Article in Chinese | WPRIM | ID: wpr-980754

ABSTRACT

OBJECTIVE@#To observe the clinical efficacy of transcutaneous electrical acupoint stimulation (TEAS) at Changqiang (GV 1) based on the modulation of electro-oculogram (EOG) signal for children with mental retardation, and explore the evaluation effect of the goal attainment scale (GAS) in children with mental retardation.@*METHODS@#Sixty children with mental retardation were randomly divided into a treatment group and a control group, with 30 cases in each one. The children in the control group were treated with conventional rehabilitation, 5 times a week. On the basis of the control group, TEAS at Changqiang (GV 1) under the modulation of EOG signal was adopted in the treatment group. When the similarity between the collected EOG signal and the template was within the range of EOG threshold, one electric stimulation was triggered at Changqiang (GV 1) for 20 s (continuous wave, 70-100 Hz in frequency, 0.1-0.2 ms in pulse width), lasting 30 min in each treatment, the intervention was given twice a week. One course of treatment was composed of 4 weeks, and 3 courses were required in total in the two groups. The infant-junior high school student's social living ability scale (S-M) and GAS were scored and compared before and after treatment in the two groups.@*RESULTS@#After treatment, the scores of self-living ability in the treatment group and communication ability in the control group were higher than those before treatment (P<0.01, P<0.05). The scores of collective activity and motor ability in the treatment group were higher than those in the control group (P<0.05). After treatment, GAS scores were higher than before treatment in both groups (P<0.001), and the score in the treatment group was higher than the control group (P<0.05).@*CONCLUSION@#TEAS under the modulation of EOG signal is conductive to improving the collective, motor and self-living abilities of the children with mental retardation and promoting children's individual goals. Compared with the standard score of S-M, the T value of GAS can better reflect the subtle progress of individual.


Subject(s)
Infant , Humans , Child , Intellectual Disability/therapy , Electrooculography , Acupuncture Points , Medicine , Electric Stimulation
10.
Journal of Central South University(Medical Sciences) ; (12): 294-301, 2023.
Article in English | WPRIM | ID: wpr-971397

ABSTRACT

Börjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked intellectual disability. The main features of the patients include intellectual disability/global developmental delay, characteristic face, anomalies of fingers and toes, hypogonadism, linear skin hyperpigmentation, and tooth abnormalities in female patients, and obesity in male patients. A case of BFLS caused by a novel mutation of PHF6 gene who was treated in the Department of Pediatrics, Xiangya Hospital, Central South University was reported. The 11 months old girl presented the following symptons: Global developmental delay, characteristic face, sparse hair, ocular hypertelorism, flat nasal bridge, hairy anterior to the tragus, thin upper lip, dental anomalies, ankyloglossia, simian line, tapering fingers, camptodactylia, and linear skin hyperpigmentation. The gene results of the second-generation sequencing technology showed that there was a novel heterozygous mutation site c.346C>T (p.Arg116*) of the PHF6 (NM032458.3), variation rating as pathogenic variation. During the follow-up, the patient developed astigmatism, strabismus, awake bruxism, and stereotyped behavior, and the linear skin hyperpigmentation became gradually more evident. The disease is lack of effective therapy so far.


Subject(s)
Humans , Male , Female , Child , Infant , Intellectual Disability/genetics , Mental Retardation, X-Linked/pathology , Obesity/complications , Hypogonadism/pathology
11.
Chinese Acupuncture & Moxibustion ; (12): 955-958, 2023.
Article in Chinese | WPRIM | ID: wpr-1007425

ABSTRACT

Insomnia induced by mental retardation is related to the synergistic dysfunction of "shaoyang, sanjiao and haishi (the period of the day from 9 pm to 11 pm) " in pathogenesis. Based on "trinity theory of shaoyang, sanjiao and haishi ", the acupoints of hand and food shaoyang meridians on the head and face (Fengchi [GB 20], Sizhukong [TE 23] and Jiaosun [TE 20]) and those on the four limbs (Sanyangluo [TE 8], Zhongzhu [TE 3], Qiuxu [GB 40] and Xiaxi [GB 43]) are selected to regulate the pivot function of shaoyang. Front-mu and back-shu points (Sanjiaoshu [BL 22], Danzhong [CV 17] and Tianshu [ST 5]), as well as auricular points (Gan [CO12], Dan [CO11] and Sanjiao [CO17]) are chosen to promote qi circulation of shaoyang and sanjiao meridians. In association with the relevant knowledge of time acupuncture at haishi, the circadian rhythm of sleep is set up and the appropriate sleep pattern is developed.


Subject(s)
Humans , Sleep Initiation and Maintenance Disorders/therapy , Intellectual Disability , Acupuncture Therapy , Meridians , Acupuncture Points
12.
Chinese Journal of Contemporary Pediatrics ; (12): 1066-1071, 2023.
Article in Chinese | WPRIM | ID: wpr-1009848

ABSTRACT

With the increase in the survival rate of very preterm infants, the long-term neurodevelopmental outcomes of such infants have attracted more and more attention. Very preterm infants tend to develop movement disorders and psychological and behavioral problems, including cerebral palsy, developmental coordination disorders, autism spectrum disorders, attention deficit hyperactivity disorders, specific learning disorders, and intellectual developmental disorders. It is of vital importance to improve the long-term prognosis of very preterm infants, and early comprehensive intervention measures can minimize disability and achieve optimal parenting outcomes. This article provides a review of the research progress on the long-term neurodevelopmental outcomes in extremely preterm infants.


Subject(s)
Infant , Female , Infant, Newborn , Humans , Infant, Extremely Premature , Autism Spectrum Disorder , Intellectual Disability , Infant, Very Low Birth Weight , Attention Deficit Disorder with Hyperactivity , Fetal Growth Retardation
13.
Chinese Journal of Medical Genetics ; (6): 1546-1550, 2023.
Article in Chinese | WPRIM | ID: wpr-1009338

ABSTRACT

OBJECTIVE@#To explore the clinical phenotype and genetic characteristics of a child with Intellectual developmental disorder with behavioral abnormalities and craniofacial malformations without epilepsy (IDDBCS).@*METHODS@#A child who had visited the Lianyungang Maternal and Child Health Care Hospital in April 2021 was selected as the study subject. Clinical data of the child were collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of his family members.@*RESULTS@#The child, a 3-year-and-4-month-old male, had presented with global developmental delay and cranial malformation. Genetic testing revealed that he has harbored a heterozygous c.1703delA (p.K568Sfs9) variant of the PHF21A gene, for which both of his parents were of the wild type. This low-frequency variant may alter the structure and function of the protein product. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was classified as a pathogenic variant (PVS1+PS2+PM2_Supporting).@*CONCLUSION@#The heterozygous c.1703delA (p.K568Sfs9) variant of the PHF21A gene probably underlay the IDDBCS in this patient.


Subject(s)
Child , Male , Humans , Infant , Developmental Disabilities/genetics , Craniofacial Abnormalities/genetics , Seizures/genetics , Intellectual Disability/genetics , Problem Behavior , Mutation
14.
Chinese Journal of Medical Genetics ; (6): 1536-1540, 2023.
Article in Chinese | WPRIM | ID: wpr-1009336

ABSTRACT

OBJECTIVE@#To explore the clinical phenotype and genetic variant in a child with Verheij syndrome (VRJS).@*METHODS@#A child who had presented at the Soochow University Affiliated Children's Hospital and Wujiang District Children's Hospital in July 2022 for "elevated scapula since early childhood" was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child had manifested elevated scapulae, torticollis, neck asymmetry, facial dysmorphism, dispersed café-au-lait spots, limited mobility of upper limbs and shoulder joints, and intellectual disability. Sequencing revealed that he has harbored a de novo heterozygous c.405dupT (p.Ile136Tyrfs*4) variant of the PUF60 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), this variant was classified as pathogenic (PVS1+PS2_moderate+PM2_supporting). Combined his clinical features and result of genetic testing, the child was diagnosed with VRJS due to variant of the PUF60 gene.@*CONCLUSION@#The clinical manifestations of VRJS include facial dysmorphism, intellectual disability, elevated scapulae, vertebral fusion, other skeletal malformations, without significant abnormalities of the heart, kidney, and eyes, which need to be distinguished from Klippel-Feil syndrome. Above finding has expended the mutation spectrum of the PUF60 gene and provided a reference for delineation of the genotype-phenotype correlation of the VRJS.


Subject(s)
Child , Child, Preschool , Humans , Male , Cafe-au-Lait Spots , Computational Biology , Genetic Testing , Genomics , Intellectual Disability/genetics , Mutation
15.
Chinese Journal of Medical Genetics ; (6): 1508-1511, 2023.
Article in Chinese | WPRIM | ID: wpr-1009330

ABSTRACT

OBJECTIVE@#To explore the clinical characteristics and genetic basis of two brothers featuring X-linked alpha thalassemia mental retardation (ATR-X) syndrome.@*METHODS@#An infant who had presented at the Qilu Children's Hospital in 2020 for unstable upright head and inability to roll over and his family were selected as the study subjects. The clinical features of the child and one of his brothers were summarized, and their genomic DNA was subjected to targeted capture and next generation sequencing (NGS).@*RESULTS@#The brothers had presented with mental retardation and facial dysmorphisms. NGS revealed that they had both harbored a hemizygous c.5275C>A variant of the ATRX gene located on the X chromosome, which was inherited from their mother.@*CONCLUSION@#The siblings were diagnosed with ATR-X syndrome. The discovery of the c.5275C>A variant has enriched the mutational spectrum of the ATRX gene.


Subject(s)
Humans , Infant , Male , alpha-Thalassemia/diagnosis , Ataxia Telangiectasia Mutated Proteins/genetics , East Asian People , Intellectual Disability/genetics , Mental Retardation, X-Linked/diagnosis , Pedigree , X-linked Nuclear Protein/genetics
16.
Chinese Journal of Medical Genetics ; (6): 1425-1429, 2023.
Article in Chinese | WPRIM | ID: wpr-1009316

ABSTRACT

OBJECTIVE@#To carry out genetic analysis for a Chinese pedigree affected with intellectual disability and overgrowth due to a supernumerary marker chromosome (sSMC).@*METHODS@#A pedigree which had presented at Jiaxing Maternity and Child Health Care Hospital on August 31, 2021 was selected as the study subject, for which chromosomal karyotyping, single nucleotide polymorphism-based microarray (SNP-array), and fluorescence in situ hybridization (FISH) were carried out in combination.@*RESULTS@#SNP-array analysis showed that the proband and his sister had both harbored a 16.1 Mb duplication which encompassed the critical region of 15q26 overgrowth syndrome. FISH confirmed that the proband was 47,XX,+neo(15)(qter→q25.3:)mat, her mother was 47,XX,del(15)(q25.3:),+neo(15)(qter→q25.3:), whilst her father was normal.@*CONCLUSION@#Application of multiple genetic techniques has facilitated delineation of the origin of sSMC and reliable genetic counseling for this pedigree.


Subject(s)
Female , Humans , Male , Chromosomes , East Asian People , In Situ Hybridization, Fluorescence , Karyotyping , Pedigree , Polymorphism, Single Nucleotide , Intellectual Disability/genetics , Chromosome Duplication/genetics
17.
Chinese Journal of Medical Genetics ; (6): 1382-1386, 2023.
Article in Chinese | WPRIM | ID: wpr-1009308

ABSTRACT

OBJECTIVE@#To summarize the clinical features and biological characteristics of Helsmoortel Van der Aa syndrome (HVDAS) due to hotspot mutations of the ADNP gene in order to facilitate early diagnosis.@*METHODS@#Clinical data and result of genetic testing for a girl with HVDAS due to hotspot mutation of the ADNP gene was summarized. Related literature was also reviewed.@*RESULTS@#The patient, a 2-year-old girl, had presented with growth retardation, facial dysmorphism, psychomotor and language delay and recurrent respiratory infections. Whole exome sequencing revealed that she has harbored a heterozygous c.2496_2499delTAAA (p.Asn832Lysfs*81) variant of the ADNP gene, which was not found in either of her parents.@*CONCLUSION@#Although the typical features of the HVDAS have included intellectual disability and autism spectrum disorders, growth retardation and premature primary tooth eruption may also be present. In addition, the phenotypic difference among individuals carrying hot spot variants of the ADNP gene was not prominent.


Subject(s)
Humans , Female , Child, Preschool , Intellectual Disability/genetics , Homeodomain Proteins/genetics , Nerve Tissue Proteins/genetics , Abnormalities, Multiple/genetics , Mutation , Rare Diseases , Growth Disorders/genetics
18.
Chinese Journal of Medical Genetics ; (6): 1146-1149, 2023.
Article in Chinese | WPRIM | ID: wpr-1009266

ABSTRACT

OBJECTIVE@#To explore the clinical characteristics and genetic etiology of a patient with mental retardation and ejaculatory dysfunction.@*METHODS@#A patient with mental retardation and ejaculatory dysfunction who was admitted to the First Affiliated Hospital of Air Force Military Medical University on November 18, 2021 was selected as the study subject. Clinical data of the patient were collected. Peripheral venous blood samples were collected from the patient and his parents. Whole exome sequencing (WES) was carried out for the patient, and the candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The patient, a 26-year-old male, had manifested atypical mental retardation and ejaculatory dysfunction. WES revealed that he has harbored a heterozygous variant of the ARID1B gene, namely c.5776C>T (p.Arg1926X). Sanger sequencing verified that neither of his parents has carried the same variant. The variant has been recorded in the 1000 Genomes, ExAC, gnomAD and ClinVar databases. A search of the dbSNP database suggested that the variant has a population frequency of 0.000 4%. The variant was predicted as deleterious by online software including Mutation Taster, CADD, and MutPred. Analysis with Cluster Omega online software suggested that the amino acid encoded by the variant site was highly conserved among various species. Analysis with PyMOL software suggested that the variant may affect the function of the encoded protein. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and ClinGen, the variant was predicted to be pathogenic.@*CONCLUSION@#The c.5776C>T (p.Arg1926X) variant of the ARID1B gene probably underlay the mental retardation and ejaculatory dysfunction in this patient. Above finding has broadened the spectrum of the ARID1B gene variants and provided reference for the diagnosis and treatment of the patient.


Subject(s)
Male , Humans , Adult , Intellectual Disability/genetics , Transcription Factors/genetics , Computational Biology , Gene Frequency , Genomics , DNA-Binding Proteins/genetics
19.
Chinese Journal of Medical Genetics ; (6): 1004-1008, 2023.
Article in Chinese | WPRIM | ID: wpr-1009248

ABSTRACT

OBJECTIVE@#To explore the genetic etiology of a child with Hypomagnesemia, epilepsy and mental retardation syndrome (HSMR).@*METHODS@#A child who was admitted to the Children's Hospital of Shandong University on July 9, 2021 due to repeated convulsions for 2 months was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his pedigree members were collected for the extraction of genomic DNA. Whole exome sequencing was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child, a 1-year-and-7-month-old male, had presented with epilepsy and global developmental delay. Serological testing revealed that he has low serum magnesium. Genetic testing showed that the child has harbored a heterozygous c.1448delT (p.Val483GlyfsTer29) variant of the CNNM2 gene, which was de novo in origin. The variant has caused substitution of the Valine at position 483 by Glycine and formation of a termination codon after 29 amino acids at downstream. As predicted by Swiss-Model online software, the variant may alter the protein structure, resulting in a truncation. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1448delT (p.Val483GlyfsTer29) was predicted as a pathogenic variant (PVS1+PS2+PM2_Supporting+PP4).@*CONCLUSION@#The heterozygous c.1448delT variant of the CNNM2 gene probably underlay the HSMR in this child. Above finding has enriched the phenotype-genotype spectrum of the CNNM2 gene.


Subject(s)
Humans , Male , Infant , Cation Transport Proteins , Computational Biology , Ethnicity , Intellectual Disability/genetics , Magnesium , Mutation , Seizures/genetics
20.
Chinese Journal of Medical Genetics ; (6): 966-972, 2023.
Article in Chinese | WPRIM | ID: wpr-1009242

ABSTRACT

OBJECTIVE@#To investigate the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Cohen syndrome.@*METHODS@#A proband who was admitted to Zhengzhou People's Hospital on June 2, 2021 due to intellectual disability and developmental delay, in addition with her younger sister and other family members, were selected as the study subjects. Clinical data of the proband and her younger sister were collected. Genomic DNA was extracted from peripheral venous blood and chorionic villi samples. Chromosomal abnormalities were detected with chromosomal microarray analysis (CMA). Whole exome sequencing (WES) and Sanger sequencing were carried out to detect candidate variants in the proband. With RNA extracted from the peripheral blood samples, VPS13B gene transcripts and expression were analyzed by PCR and real-time quantitative PCR. Prenatal diagnosis was carried out at 12 weeks' gestation.@*RESULTS@#The proband was a 10-year-old female with clinical manifestations including development delay, obesity, severe myopia and peculiar facial features. Her sister was 3 years old with a similar phenotype. CMA revealed no chromosomal abnormality in the proband, while WES results revealed that the proband and her sister had both harbored compound heterozygous variants of the VPS13B gene, namely c.10076_10077delCA (p.T3359fs*29) and c.6940+1G>T, which were respectively inherited from their mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+PS4+PM4+PP1; PVS1+PM2_Supporting+PM3+PP1). In vivo splicing assay confirmed that the c.6940+1G>T variant has produced a frameshift transcript with skipping of exon 38. Compared with the control group, the expression of RNA in the peripheral blood of the proband's parents has decreased to 65% ~ 70% (P < 0.01), whilst that in the proband and her sister has decreased to 40% (P < 0.001). Prenatal diagnosis at 12 weeks of gestation has found that the fetus only harbored the heterozygous c.10076_ 10077delCA variant.@*CONCLUSION@#The c.10076_10077delCA (p.T3359fs*29) frameshift variant and c.6940+1G>T splicing variant probably underlay the Cohen syndrome in this pedigree. Genetic testing has facilitated the diagnosis of this disease.


Subject(s)
Female , Humans , Child, Preschool , Child , East Asian People , Intellectual Disability/genetics , Mutation , Myopia/genetics , Pedigree , Vesicular Transport Proteins/genetics
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