OBJECTIVE: To explore the genetic etiology for a child featuring mental retardation and speech delay. METHODS: Clinical data of the child was collected. DNA was extracted from peripheral blood samples of the child and members of his pedigree. Whole exome sequencing was carried out for the child, and candidate variants were verified by Sanger sequencing. Prenatal diagnosis was provided for his mother upon her subsequent pregnancy. RESULTS: The child has mainly featured mental retardation, speech delay, ptosis, strabismus, photophobia, hyperactivity, and irritability. Whole exome sequencing revealed that he has harbored a pathogenic heterozygous variant of the KAT6A gene, namely c.5314dupA (p.Ser1772fs*20), which was not detected in either of his parents. The child was diagnosed with Arboleda-Tham syndrome. The child was also found to harbor a hemizygous c.56T>G (p.Leu19Trp) variant of the AIFM1 gene, for which his mother was heterozygous and his phenotypically normal maternal grandfather was hemizygous. Pathogenicity was excluded. Prenatal diagnosis has excluded the c.5314dupA variant of the KAT6A gene in the fetus. CONCLUSION The heterozygous c.5314dupA (p.Ser1772fs*20) variant of the KAT6A gene probably underlay the Arboleda-Tham syndrome in this child. Above finding has enabled genetic counseling and prenatal diagnosis for this pedigree.
Child ; Humans ; Male ; Pregnancy ; Histone Acetyltransferases ; Intellectual Disability/genetics* ; Language Development Disorders ; Pedigree

OBJECTIVE: To analyze the clinical features and genetic basis of three children with mental retardation, language impairment and autistic features due to de novo variants of FOXP1 gene. METHODS: Clinical data of the children were collected.Trio-whole exome sequencing was carried out for the children and their parents. Pathogenicity of the variants was analyzed through bioinformatics prediction. RESULTS: All of the children had various degrees of mental retardation in conjunct with language deficit, global developmental delay, abnormal behavior and peculiar facial features, among whom two also developed autism spectrum disorders. The results of genetic testing showed that all three children harbored de novo variants of the FOXP1 gene, namely c.613_c.614delCTinsTA, c.1248delC and c.1393A>G. Two of these were frameshift variants and one was missense variant, which were all rated as pathogenic based on the guidelines of the American College of Medical Genetics (ACMG). Database search suggested that c.613_c.614delCTinsTA and c.1248delC were unreported previously. CONCLUSION For the three children from unrelated families with mental retardation in conjunct with language deficit, global growth delay, abnormal behavior and peculiar facial features, the c.613_ c. 614delCTinsTA, c.1248delC and c.1393A>G variants of the FOXP1 gene may be the pathogenic factors. Above cases have further expanded the genotype-phenotype profile of FOXP1 deficiency syndrome.
Autistic Disorder/genetics* ; Child ; Forkhead Transcription Factors/genetics* ; Genetic Testing ; Humans ; Intellectual Disability/genetics* ; Language Development Disorders/genetics* ; Repressor Proteins/genetics* ; Whole Exome Sequencing

OBJECTIVE: To describe a family with intellectual developmental disorder with autism and speech delay (IDDAS) caused by a splice variant of TBR1 gene. METHODS: A pregnant women with mental retardation, who also had a family history of mental retardation, was admitted to Prenatal Diagnosis Center of WanBei Coal and Electricity Group General Hospital Corporation in April 2019. Molecular genetic tests were performed on the pregnant women and ten other family members to analyze the pathogenic genotype. Functional assays of the pathogenic variant was carried out by minigene technology. With the determination of the genotype, prenatal diagnosis was carried out by amniotic fluid sampling. RESULTS: Through whole exome sequencing, a novel splicing variant (c.1129-1G>C) was identified in the TBR1 gene of the proband, which has co-segregated with the disease phenotype in the family. The results of minigene assay showed abnormal splicing of exon 5. The variant was not detected in the fetal amniotic fluid. Fetal growth and development were normal one year after the birth. CONCLUSION The c.1129-1G>C variant of the TBR1 probably underlay the disease in of the pedigree. Timely prenatal genetic diagnosis and consultation can help to stop the transmission of the pathogenic variant.
Autistic Disorder/genetics* ; China ; Developmental Disabilities ; Female ; Humans ; Infant ; Intellectual Disability/genetics* ; Language Development Disorders ; Pedigree ; Pregnancy ; T-Box Domain Proteins/genetics*

In patients with a language developmental delay, it is necessary to make a differential diagnosis for autism spectrum disorders (ASDs), specific language impairment, and mental retardation. It is important that pediatricians recognize the signs and symptoms of ASDs, as many patients with language developmental delays are ultimately diagnosed with ASDs. Pediatricians play an important role in the early recognition of ASDs, because they are usually the first point of contact for children with ASDs. A revision of the diagnostic criteria of ASDs was proposed in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) that was released in May 2013. The autism spectrum describes a range of conditions classified as neurodevelopmental disorders in the fifth edition of the DSM. The new diagnostic criteria encompasses previous elements from the diagnosis of autistic disorder, Asperger disorder, childhood disintegrative disorder, and pervasive developmental disorder-not otherwise specified. An additional change to the DSM includes synthesizing the section on social and communication deficits into one domain. In ASD patients, the appropriate behavioral therapies and rehabilitation treatments significantly affect the prognosis. Therefore, this makes early diagnosis and treatment very important. In conclusion, pediatricians need to be able to recognize the signs and symptoms of ASDs and be attentive to them in order to make an early diagnosis and provide treatment.
Asperger Syndrome ; Autistic Disorder ; Child ; Autism Spectrum Disorder* ; Developmental Disabilities ; Diagnosis ; Diagnosis, Differential ; Diagnostic and Statistical Manual of Mental Disorders ; Early Diagnosis ; Genetics ; Humans ; Intellectual Disability ; Language Development ; Prognosis ; Rehabilitation

OBJECTIVE: To explore the clinical and genetic characteristics of a boy with isolated maternal uniparental disomy of chromosome 20 [UPD(20)mat]. METHODS: A child who was admitted to the Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology on April 8,2021. was selected as the study subject. Phenotypic and endocrinological findings of the child were retrospectively analyzed. Whole exome sequencing (WES) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) were carried out for detecting the UPD sequences and copy number variations. Both of his parents were verified by Sanger sequencing. Relevant literature was systematically reviewed. RESULTS: The child, a 3-year-and-8-month-old boy born to a 41-year-old mother by Cesarean delivery at 36⁺² gestational weeks due to oligohydramia, had a birth weight of 2 300 g and length of 46 cm. He was admitted to the NICU for feeding difficulties which had persisted despite of clinical management. At the age of 3.75, he had a height of 92.5 cm (< 3rd percentile; 25th ~ 50th percentile at 2.5 years) and a weight of 10.8 kg (< 3rd percentile; 50th percentile at 15 months). He had also presented with growth retardation, short stature, attention deficit and hyperactivity disorder (ADHD), mild mental retardation, and speech and language development disorders. He had simian creases in both hands but no additional dysmorphic signs, and his motor development was normal. Serum insulin, thyroid-stimulating hormone, and insulin growth factor binding protein 3 levels were within the normal ranges, though insulin growth factor-1 (IGF-1) was slightly decreased. Since that time he had continuously used atomoxetine hydrochloride capsules to control his ADHD. WES and MS-MLPA revealed the existence of UPD (20)mat. CONCLUSION The UPD(20)mat syndrome is characterized by feeding difficulties, growth retardation and short stature. The child in our case has been accompanied by ADHD and speech and language development disorders, which required long-term treatment. For women with advanced maternal age and suggestive phenotypes, genetic testing and counseling should be conducted.
Male ; Pregnancy ; Humans ; Child ; Female ; Infant ; Adult ; Chromosomes, Human, Pair 20 ; DNA Copy Number Variations ; Retrospective Studies ; Uniparental Disomy/genetics* ; Atomoxetine Hydrochloride ; Dwarfism ; Intercellular Signaling Peptides and Proteins ; Language Development Disorders ; Growth Disorders ; Insulins