Gene intellectual disability

INTRODUCTION: BRPF1 gene on 3p26-p25 encodes a protein involved in epigenetic regulation, through interaction with histone H3 lysine acetyltransferases KAT6A and KAT6B of the MYST family. Heterozygous pathogenic variants in BRPF1 gene are associated with Intellectual Developmental Disorder with Dysmorphic Facies and Ptosis (IDDDFP), characterized by global developmental delay, intellectual disability, language delay, and dysmorphic facial features. The reported ocular involvement includes strabismus, amblyopia, and refraction errors...

INTRODUCTION: Horizontal gaze palsy with progressive scoliosis-2 (HGPPS2, MIM 617542) with impaired intellectual development aka developmental split-brain syndrome is an ultra-rare congenital disorder caused by pathogenic biallelic variants in the deleted in colorectal cancer ( DCC ) gene. CASE PRESENTATION: We report the clinical and genetic characterization of a Syrian patient with a HGPPS2 phenotype and review the previously published cases of HGPPS2. The genetic screening was performed using exome sequencing on Illumina platform...

INTRODUCTION: SETBP1 gene variants that decrease or eliminate protein activity have been associated with phenotypes characterized by speech apraxia and intellectual disabilities. This condition, distinctly separated from Schinzel-Giedion syndrome, is referred to as autosomal dominant mental retardation 29 (ADR29). CASE PRESENTATION: In this report, we present the case of a 6-year-old male patient exhibiting fine and global motor skill impairments along with expressive language delay...

INTRODUCTION: Currarino syndrome is a rare syndrome with multiple congenital anomalies including sacral agenesis, anorectal malformation, and presence of a presacral mass. Currarino syndrome is considered to be an autosomal dominant inherited disorder, with low penetrance and variable expressivity, but sporadic cases have also been reported. Mutations in MNX1 gene, mapped to 7q36, are the main causes of this syndrome. To the best of our knowledge, less than 400 cases of this syndrome have been mentioned in the literature...

We present for the first-time efficacy and tolerability of GLP-1-RA (Semaglutide) in Smith-Kingsmore syndrome (SKS). SKS is a rare genetic disorder characterized by intellectual disability, macrocephaly, seizures and distinctive facial features due to MTOR gene mutation. We present a 22-year-old woman with mosaic SKS and severe obesity (Body Mass Index ≥40 kg/m²), treated with semaglutide. She achieved a 9 kg (7.44%) weight loss over 12 months without adverse effects.This case highlights semaglutide's potential in managing obesity in SKS patients, emphasizing the need for further research in this rare genetic disorder...

BACKGROUND: Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder caused by loss-of-function mutations of the NTRK1 gene, affecting the autonomic and sensory nervous system. Clinical manifestation is varied and includes recurrent fever, pain insensitivity, anhidrosis, self-mutilating behavior, and intellectual disability. METHODS: Clinical and genetic features were assessed in two males and one female with genetically confirmed CIPA using exome or genome sequencing...

PURPOSE: The purpose of this study was to characterize the phenotype associated with a de novo gain-of-function variant in the GUCY1A2 gene. METHODS: An individual carrying the de novo heterozygous variant c.1458G>T p.(E486D) in GUCY1A2 was identified by exome sequencing. The effect of the corresponding enzyme variant α2E486D/β1 was evaluated using concentration-response measurements with wild-type enzyme and the variant in cytosolic fractions of HEK293 cells, UV-vis absorbance spectra of the corresponding purified enzymes, and examination of overexpressed fluorescent protein-tagged constructs by confocal laser scanning microscopy...

The SYN1 gene encodes synapsin I, variants within the SYN1 gene are linked to X-linked neurodevelopmental disorders with high clinical heterogeneity, with reflex epilepsies (REs) being a representative clinical manifestation. This report analyzes a Chinese pedigree affected by seizures associated with SYN1 variants and explores the genotype-phenotype correlation. The proband, a 9-year-old boy, experienced seizures triggered by bathing at the age of 3, followed by recurrent absence seizures, behavioral issues, and learning difficulties...

BACKGROUND: Autosomal recessive primary microcephaly (MCPH) is a rare neurodevelopmental disorder characterized primarily by congenital microcephaly and intellectual disability but without extra-central nervous system malformations. This investigation aimed to elucidate the genetic underpinnings of microcephaly in a patient from a Chinese consanguineous family. METHODS: A comprehensive clinical assessment, including brain magnetic resonance imaging (MRI), electroencephalogram (EEG), and genetic analyses, was conducted to evaluate the patient's condition...

The histone lysine demethylase KDM5B is implicated in recessive intellectual disability disorders and heterozygous, protein truncating variants in KDM5B are associated with reduced cognitive function in the population. The KDM5 family of lysine demethylases has developmental and homeostatic functions in the brain, some of which appear to be independent of lysine demethylase activity. To determine the functions of KDM5B in hippocampus-dependent learning and memory, we first studied male and female mice homozygous for a Kdm5b Δ ARID allele that lacks demethylase activity...

BACKGROUND: We report here the clinical and genetic features of KMT5B -related neurodevelopmental disorder caused by a novel heterozygous frameshift variant in KMT5B in a Chinese family. CASE PRESENTATION: A 7-year-old Chinese boy with mild-to-moderate intellectual disability, significant language impairment, motor disability, and coordination difficulties presented to our hospital because he "could not speak and did not look at others." He was diagnosed with autism spectrum disorder previously owing to developmental delays in cognition, language expression, and understanding...

Sequence variants in the HERC2 gene are associated with a significant reduction in HERC2 protein levels and cause a neurodevelopmental disorder known as the HERC2-related disorder, which shares clinical features with Angelman syndrome, including global developmental delay, intellectual disability, autism, and movement disorders. Remarkably, the HERC2 gene is commonly deleted in individuals with Angelman syndrome, suggesting a potential contribution of HERC2 to the pathophysiology of this disease. Given the known critical role of autophagy in brain development and its implication in neurodevelopmental diseases, we undertook different experimental approaches to monitor autophagy in fibroblasts derived from individuals affected by the HERC2-related disorder...

Angelman syndrome (AS) is a rare neurodevelopmental disorder due to genetic defects involving chromosome 15, known by intellectual disability, cognitive and behavioral disorders, ataxia, delayed motor development, and seizures. This study highlights the clinical spectrum and molecular research to establish the genotype-phenotype correlation in the pediatric Moroccan population. Methylation-specific-polymerase chain reaction (MS-PCR) is a primordial technique not only to identify the genetic mechanism of AS but also to characterize the different molecular classes induced in the appearance of the clinical symptoms...

Spondyloenchondrodysplasia (SPENCD) is a rare spondylometaphyseal skeletal dysplasia with characteristic lesions mimicking enchondromatosis and resulting in short stature. A large spectrum of immunologic abnormalities may be seen in SPENCD, including immune deficiencies and autoimmune disorders. SPENCD is caused by loss of tartrate-resistant acid phosphatase activity, due to homozygous mutations in ACP5 , playing a role in nonnucleic-acid-related stimulation/regulation of the type I interferon pathway. In this article, we presented a 19-year-old boy with SPENCD, presenting with recurrent autoimmune hemolytic anemia episodes since he was 5 years old...

Chromatinopathy is an emerging category of multiple malformation syndromes caused by disruption in global transcriptional regulation with imbalances in the chromatin states (i.e., open or closed chromatin). These syndromes are caused by pathogenic variants in genes coding for the writers, erasers, readers, and remodelers of the epigenetic machinery. Majority of these disorders (93%) show neurological dysfunction in the form of intellectual disability. Other overlapping features are growth abnormalities, limb deformities, and immune dysfunction...

BACKGROUND: Glutamatergic synapse dysfunction is believed to underlie the development of Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) in many individuals. However, identification of genetic markers that contribute to synaptic dysfunction in these individuals is notoriously difficult. Based on genomic analysis, structural modeling, and functional data, we recently established the involvement of the TRIO-RAC1 pathway in ASD and ID. Furthermore, we identified a pathological de novo missense mutation hotspot in TRIO's GEF1 domain...

BACKGROUND: Zhu-Tokita-Takenouchi-Kim syndrome (ZTTK syndrome) is a severe multi-systemic developmental disorder, caused by variants in the SON gene. A patient diagnosed with ZTTK syndrome who carried a de novo SON mutation and exhibited recurrent myocardial injury was described in this case. CASE PRESENTATION: A 7-year-old girl was admitted to the Cardiology Department of Beijing Children's Hospital in November 2019 due to myocardial injury following respiratory infection...

LINS1 is the human homolog of the Drosophila segment polarity gene that encodes an essential regulator of the wingless/Wnt signaling. By 2011, only seven pedigrees (16 patients) with eight causative variants in LINS1 gene have been reported. These cases mainly presented with infancy-/child-onset neurodevelopmental disorders, facial dysmorphia, and other clinical features, and a wide spectrum of clinically distinct phenotypes were also manifested. In our study, two brothers in a family were admitted and diagnosed with child-onset movement disorders, slight intellectual disability, psychological symptoms, eye problems, urinary and bowel dysfunction, mitral value prolapse, and Q-T prolongation...

The clinical and genetic characteristics of SYNGAP1 mutations in Korean pediatric patients are not well understood. We retrospectively analyzed 13 individuals with SYNGAP1 mutations from a longitudinal aspect. Clinical data, genetic profiles, and electroencephalography (EEG) patterns were examined. Genotypic analyses included gene panels and whole-exome sequencing. All patients exhibited global developmental delay from early infancy, with motor development eventually reaching independent ambulation by 3 years of age...

BACKGROUND: Mandibulofacial dysostosis with microcephaly (MFDM, OMIM# 610536) is a rare monogenic disease that is caused by a mutation in the elongation factor Tu GTP binding domain containing 2 gene (EFTUD2, OMIM* 603892). It is characterized by mandibulofacial dysplasia, microcephaly, malformed ears, cleft palate, growth and intellectual disability. MFDM can be easily misdiagnosed due to its phenotypic overlap with other craniofacial dysostosis syndromes. The clinical presentation of MFDM is highly variable among patients...