Pathogenic missense variants affecting p.Gly392 have variable functional implications and result in diverse clinical phenotypes.

-associated syndrome (SAS) is caused by pathogenic variants in , which encodes an evolutionarily conserved transcription factor. Despite the broad range of phenotypic manifestations and variable severity related to this syndrome, haploinsufficiency has been assumed to be the primary molecular explanation.In this study, we describe eight individuals with variants that affect p.

Abnormalities in pharyngeal arch-derived structures in SATB2-associated syndrome.

SATB2-associated syndrome (SAS, glass syndrome, OMIM#612313) is a neurodevelopmental autosomal dominant disorder with frequent craniofacial abnormalities including palatal and dental anomalies. To assess the role of Satb2 in craniofacial development, we analyzed mutant mice at different stages of development. Here, we show that Satb2 is broadly expressed in early embryonic mouse development including the mesenchyme of the second and third arches.

Bone health in SATB2-associated syndrome: Results from a large prospective cohort and recommendations for surveillance.

Alterations in SATB2 result in SATB2-associated syndrome (SAS; Glass syndrome, OMIM 612313), an autosomal dominant multisystemic disorder predominantly characterized by developmental delay, craniofacial anomalies, and growth retardation. The bone phenotype of SAS has been less explored until recently and includes a variety of skeletal deformities, increased risk of low bone mineral density (BMD) with a propensity to fractures, and other biochemical abnormalities that suggest elevated bone turnover. We present the results of ongoing surveillance of bone health from 32 individuals (47% females, 3-18 years) with molecularly-confirmed SAS evaluated at a multidisciplinary clinic.

Growth in individuals with SATB2-associated syndrome.

SATB2-associated syndrome (SAS) is an autosomal dominant multisystemic disorder caused by alterations in the SATB2 gene. In addition to a predominant neurodevelopmental phenotype, individuals with SAS often present with feeding difficulties and growth retardation that persist past infancy. In this study, we present growth and measurement data from 211 individuals (53.

coding variants in the gene cause a neurodevelopmental disorder with intellectual disability.

Background: High-impact pathogenic variants in more than a thousand genes are involved in Mendelian forms of neurodevelopmental disorders (NDD).

Methods: This study describes the molecular and clinical characterisation of 28 probands with NDD harbouring heterozygous coding variants, occurring de novo for all those whose transmission could have been verified (26/28).

Results: A total of 15 unique variants leading to amino acid changes or deletions were identified: 12 missense variants, two in-frame deletions of one codon, and one canonical splice variant leading to a deletion of two amino acid residues.

Case Report: -Associated Syndrome Overlapping With Clinical Mitochondrial Disease Presentation: Report of Two Cases.

-associated syndrome (SAS) is an autosomal dominant neurogenetic multisystemic disorder. We describe two individuals with global developmental delay and hypotonia who underwent an extensive evaluation to rule out an underlying mitochondrial disorder before their eventual diagnosis of SAS. Although the strict application of the clinical mitochondrial disease score only led to the designation of "possible" mitochondrial disorder for these two individuals, other documented abnormalities included nonspecific neuroimaging findings on magnetic resonance imaging and magnetic resonance spectroscopy, decreased complex I activity on muscle biopsy for patient 2, and variation in the size and relative proportion of types of muscle fibers in the muscle biopsies that were aligned with mitochondrial diseases.

SATB2-associated syndrome in adolescents and adults.

The goal of this study was to investigate the medical, communication, activities of daily living (ADLs), and mental health concerns affecting adolescents and adults with SATB2-associated syndrome (SAS). A comprehensive questionnaire was administered to the caregivers of 49 individuals 12 years or older with SAS (mean age was 19.4 years, range 12-37 years).

Individuals with SATB2-associated syndrome with and without autism have a recognizable metabolic profile and distinctive cellular energy metabolism alterations.

SATB2-associated syndrome (SAS) is a multisystemic disorder characterized by developmental delay often with concurrent autistic tendencies. This study aimed to characterize cellular metabolic pathways and energy metabolism from cells derived from individuals with SAS. The cellular production of NADH (nicotinamide adenine dinucleotide, reduced form) as determined by the Phenotype Mammalian MicroArrays was measured in lymphoblastoid cell lines derived from 11 subjects with a molecularly confirmed diagnosis of SAS and compared to a control population of 50 age-matched typically developing individuals.

Growth, development, and phenotypic spectrum of individuals with deletions of 2q33.1 involving SATB2.

SATB2-Associated syndrome (SAS) is an autosomal dominant, multisystemic, neurodevelopmental disorder due to alterations in SATB2 at 2q33.1. A limited number of individuals with 2q33.

JARID2 haploinsufficiency is associated with a clinically distinct neurodevelopmental syndrome.

Purpose: JARID2, located on chromosome 6p22.3, is a regulator of histone methyltransferase complexes that is expressed in human neurons. So far, 13 individuals sharing clinical features including intellectual disability (ID) were reported with de novo heterozygous deletions in 6p22-p24 encompassing the full length JARID2 gene (OMIM 601594).

Genetic counseling graduate training to address religion and spirituality in clinical practice: A qualitative exploration of programs in North America.

Patients receiving clinical genetics services often navigate emotionally difficult situations and may utilize their faith as a source of support, an aid in decision-making, or a core coping strategy. Although patients have expressed interest in discussing their religious or spiritual (R/S) beliefs with their genetic counselor (GC), GCs may avoid such conversations because they feel they do not have the necessary skills to discuss R/S beliefs (Reis, Baumiller, Scrivener, Yager, & Warren, 2007). This qualitative study explored how GC programs in North America currently prepare their students to discuss R/S matters with their patients.

Epilepsy and Electroencephalographic Abnormalities in SATB2-Associated Syndrome.

Background: Seizures are an under-reported feature of the SATB2-associated syndrome phenotype. We describe the electroencephalographic findings and seizure semiology and treatment in a population of individuals with SATB2-associated syndrome.

Methods: We performed a retrospective review of 101 individuals with SATB2-associated syndrome who were reported to have had a previous electroencephalographic study to identify those who had at least one reported abnormal result.

Recurrent arginine substitutions in the ACTG2 gene are the primary driver of disease burden and severity in visceral myopathy.

Visceral myopathy with abnormal intestinal and bladder peristalsis includes a clinical spectrum with megacystis-microcolon intestinal hypoperistalsis syndrome and chronic intestinal pseudo-obstruction. The vast majority of cases are caused by dominant variants in ACTG2; however, the overall genetic architecture of visceral myopathy has not been well-characterized. We ascertained 53 families, with visceral myopathy based on megacystis, functional bladder/gastrointestinal obstruction, or microcolon.

Mutation update for the SATB2 gene.

SATB2-associated syndrome (SAS) is an autosomal dominant neurodevelopmental disorder caused by alterations in the SATB2 gene. Here we present a review of published pathogenic variants in the SATB2 gene to date and report 38 novel alterations found in 57 additional previously unreported individuals. Overall, we present a compilation of 120 unique variants identified in 155 unrelated families ranging from single nucleotide coding variants to genomic rearrangements distributed throughout the entire coding region of SATB2.

Dental radiographic findings in 18 individuals with SATB2-associated syndrome.

Objective: To characterize the radiographic dental phenotype of individuals with SATB2-associated syndrome (SAS).

Materials And Methods: Participants were evaluated by a multidisciplinary team during a concurrent clinic conducted during the 1st international SAS family meeting held in 2017 at a single institution. Whenever possible, panoramic and/or periapical radiographs were obtained in clinic or previously obtained and provided by the caregiver.

De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability.

Calcium/calmodulin-dependent protein kinase II (CAMK2) is one of the first proteins shown to be essential for normal learning and synaptic plasticity in mice, but its requirement for human brain development has not yet been established. Through a multi-center collaborative study based on a whole-exome sequencing approach, we identified 19 exceedingly rare de novo CAMK2A or CAMK2B variants in 24 unrelated individuals with intellectual disability. Variants were assessed for their effect on CAMK2 function and on neuronal migration.

Severe Metabolic Acidosis and Hepatopathy due to Leukoencephalopathy with Thalamus and Brainstem Involvement and High Lactate.

Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) is a recently described autosomal recessive mitochondrial disease characterized by early onset of neurological symptoms, a biphasic clinical course, and distinctive neuroimaging. Pathogenic variants in the gene that encode for mitochondrial glutamyl-tRNA synthetase are responsible for LTBL. Here, we describe the clinical course of an infant diagnosed with an acute crisis of LTBL and severe liver disease.

COL1A1 and COL1A2 sequencing results in cohort of patients undergoing evaluation for potential child abuse.

Child abuse is a major public health concern that can explain a proportion of fractures in children. Osteogenesis imperfecta (OI) is the most common inherited syndrome that predisposes to skeletal fractures. We conducted a retrospective analysis of data from clinical, laboratory, and radiographic information from children evaluated for child abuse in which molecular testing for COL1A1 and COL1A2 genes was conducted.