Publications by authors named "Jiddeke van de Kamp"

Article Synopsis
  • - The study analyzed 127 individuals from 16 medical centers across 6 countries to examine the relationship between TMPRSS3 gene variants and hearing loss, revealing 47 unique variants and their impact on hearing thresholds.
  • - Individuals carrying missense variants showed different hearing loss progression rates and performance in speech recognition tests post-cochlear implant, with age at implantation being a critical factor.
  • - This research represents the largest investigation into TMPRSS3 genotype-phenotype correlations, offering valuable insights for genetic counseling and developing new treatments for hearing loss.
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Sulfate is an important anion as sulfonation is essential in modulation of several compounds, such as exogens, polysaccharide chains of proteoglycans, cholesterol or cholesterol derivatives and tyrosine residues of several proteins. Sulfonation requires the presence of both the sulfate donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS) and a sulfotransferase. Genetic disorders affecting sulfonation, associated with skeletal abnormalities, impaired neurological development and endocrinopathies, demonstrate the importance of sulfate.

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Pathogenic variants in SLC6A8, the gene which encodes creatine transporter SLC6A8, prevent creatine uptake in the brain and result in a variable degree of intellectual disability, behavioral disorders (e.g., autism spectrum disorder), epilepsy, and severe speech and language delay.

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Purpose: Coffin-Siris and Nicolaides-Baraitser syndromes are recognizable neurodevelopmental disorders caused by germline variants in BAF complex subunits. The SMARCC2 BAFopathy was recently reported. Herein, we present clinical and molecular data on a large cohort.

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Glutaminase (GLS) hyperactivity was first described in 2019 in a patient with profound developmental delay and infantile cataract. Here, we describe a 4-year-old boy with GLS hyperactivity due to a de novo heterozygous missense variant in , detected by trio whole exome sequencing. This boy also exhibits developmental delay without dysmorphic features, but does not have cataract.

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Sulfate plays a pivotal role in numerous physiological processes in the human body, including bone and cartilage health. A role of the anion transporter SLC26A1 (Sat1) for sulfate reabsorption in the kidney is supported by the observation of hyposulfatemia and hypersulfaturia in Slc26a1-knockout mice. The impact of SLC26A1 on sulfate homeostasis in humans remains to be defined.

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Sulfate is the fourth most abundant anion in human plasma but is not measured in clinical practice and little is known about the consequences of sulfate deficiency. Nevertheless, sulfation plays an essential role in the modulation of numerous compounds, including proteoglycans and steroids. We report the first patient with a homozygous loss-of-function variant in the SLC13A1 gene, encoding a renal and intestinal sulfate transporter, which is essential for maintaining plasma sulfate levels.

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Chromatin is essentially an array of nucleosomes, each of which consists of the DNA double-stranded fiber wrapped around a histone octamer. This organization supports cellular processes such as DNA replication, DNA transcription, and DNA repair in all eukaryotes. Human histone H4 is encoded by fourteen canonical histone H4 genes, all differing at the nucleotide level but encoding an invariant protein.

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Article Synopsis
  • Semaphorins and plexins, important for brain development, include the PLXNA3 gene, which affects brain signaling and is linked to conditions like autism and intellectual disabilities in boys with specific genetic variants.
  • This study examined 14 boys with these hemizygous PLXNA3 variants, finding a range of issues such as autism, motor difficulties, and seizures, highlighting a connection between the gene variations and the severity of neurodevelopmental disorders.
  • The findings suggest a potential new X-linked intellectual disability syndrome tied to PLXNA3 variants and emphasize the need for more research on their impact in humans.
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Non-Syndromic Hereditary Hearing Loss (NSHHL) is a genetically heterogeneous sensory disorder with about 120 genes already associated. Through exome sequencing (ES) and data aggregation, we identified a family with six affected individuals and one unrelated NSHHL patient with predicted-to-be deleterious missense variants in USP48. We also uncovered an eighth patient presenting unilateral cochlear nerve aplasia and a de novo splice variant in the same gene.

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In mammals, sound is detected by mechanosensory hair cells that are activated in response to vibrations at frequency-dependent positions along the cochlear duct. We demonstrate that inner ear supporting cells provide a structural framework for transmitting sound energy through the cochlear partition. Humans and mice with mutations in GAS2, encoding a cytoskeletal regulatory protein, exhibit hearing loss due to disorganization and destabilization of microtubule bundles in pillar and Deiters' cells, two types of inner ear supporting cells with unique cytoskeletal specializations.

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Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported.

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There has been one previous report of a cohort of patients with variants in Chromodomain Helicase DNA-binding 3 (CHD3), now recognized as Snijders Blok-Campeau syndrome. However, with only three previously-reported patients with variants outside the ATPase/helicase domain, it was unclear if variants outside of this domain caused a clinically similar phenotype. We have analyzed 24 new patients with CHD3 variants, including nine outside the ATPase/helicase domain.

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Variants in the KIF1A gene can cause autosomal recessive spastic paraplegia 30, autosomal recessive hereditary sensory neuropathy, or autosomal (de novo) dominant mental retardation type 9. More recently, variants in KIF1A have also been described in a few cases with autosomal dominant spastic paraplegia. Here, we describe 20 KIF1A variants in 24 patients from a clinical exome sequencing cohort of 347 individuals with a mostly 'pure' spastic paraplegia.

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SLC35A2-CDG is caused by mutations in the X-linked SLC35A2 gene encoding the UDP-galactose transporter. SLC35A2 mutations lead to hypogalactosylation of N-glycans. SLC35A2-CDG is characterized by severe neurological symptoms and, in many patients, early-onset epileptic encephalopathy.

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ATP2B2 encodes the PMCA2 Ca pump that plays an important role in maintaining ion homeostasis in hair cells among others by extrusion of Ca from the stereocilia to the endolymph. Several mouse models have been described for this gene; mice heterozygous for loss-of-function defects display a rapidly progressive high-frequency hearing impairment. Up to now ATP2B2 has only been reported as a modifier, or in a digenic mechanism with CDH23 for hearing impairment in humans.

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Article Synopsis
  • Genomics methods have greatly enhanced the understanding of Mendelian disorders, especially when combined with high-throughput functional-omics technologies, leading to better identification of genetic variants in families with recessive inheritance.
  • In a study of 99 individuals with abnormal Golgi glycosylation, 31 cases underwent whole-exome sequencing, revealing a known defect in 15 individuals, while unique glycomics signatures helped identify four patients with shared genetic markers.
  • Affected siblings had mutations in the SLC10A7 gene, leading to conditions like amelogenesis imperfecta and skeletal dysplasia, with studies in zebrafish and fibroblasts showcasing the gene's crucial role in bone mineralization and glycoprotein transport.
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Since Garrod's first description of alkaptonuria in 1902, and newborn screening for phenylketonuria introduced in the 1960s, P4 medicine (preventive, predictive, personalized, and participatory) has been a reality for the clinician serving patients with inherited metabolic diseases. The era of high-throughput technologies promises to accelerate its scale dramatically. Genomics, transcriptomics, epigenomics, proteomics, glycomics, metabolomics, and lipidomics offer an amazing opportunity for holistic investigation and contextual pathophysiologic understanding of inherited metabolic diseases for precise diagnosis and tailored treatment.

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DFNB28 is characterized by prelingual, severe to profound sensorineural hearing impairment (HI). It is associated with mutations in exon 6 and 7 of TRIOBP and has not been reported in the European population. Here, we describe two isolated cases of Dutch origin with congenital, moderate HI and compound heterozygous mutations in TRIOBP.

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Hearing impairment (HI) is genetically heterogeneous which hampers genetic counseling and molecular diagnosis. Testing of several single HI-related genes is laborious and expensive. In this study, we evaluate the diagnostic utility of whole-exome sequencing (WES) targeting a panel of HI-related genes.

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Article Synopsis
  • The study investigates balanced chromosomal abnormalities (BCAs) in 273 individuals with congenital anomalies using whole-genome sequencing to achieve higher resolution than traditional karyotyping.
  • The findings revealed that 93% of karyotypes were revised, with 21% of BCAs showing complexity not detectable by standard methods, highlighting the limitations of cytogenetics.
  • The research indicated that 33.9% of BCAs caused gene disruption tied to developmental issues, and some breakpoints affected crucial genomic regions, possibly worsening conditions like 5q14.3 microdeletion syndrome due to altered gene expression.
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Article Synopsis
  • * All patients displayed varying degrees of cognitive impairment, with common issues like microcephaly, feeding difficulties, and some congenital malformations, while adults showed generally good health with friendly behavior patterns.
  • * The findings suggest a strong correlation between specific genetic mutations and the severity of symptoms, indicating that AUTS2 syndrome has distinct characteristics that can aid in diagnosis and understanding the condition.
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A variety of pathologies can underlie early-onset severe encephalopathy with epilepsy. To aid the diagnostic process in such patients we present an overview of causes, including the rapidly expanding list of genes involved. When no explanation is found, whole-exome sequencing (WES) can be used in an attempt to identify gene defects in patients suspected to suffer from a genetic form.

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Mandibulofacial dysostosis with microcephaly (MFDM) is a multiple malformation syndrome comprising microcephaly, craniofacial anomalies, hearing loss, dysmorphic features, and, in some cases, esophageal atresia. Haploinsufficiency of a spliceosomal GTPase, U5-116 kDa/EFTUD2, is responsible. Here, we review the molecular basis of MFDM in the 69 individuals described to date, and report mutations in 38 new individuals, bringing the total number of reported individuals to 107 individuals from 94 kindreds.

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Background: Urinary concentrations of creatine and guanidinoacetic acid divided by creatinine are informative markers for cerebral creatine deficiency syndromes (CDSs). The renal excretion of these substances varies substantially with age and sex, challenging the sensitivity and specificity of postanalytical interpretation.

Methods: Results from 155 patients with CDS and 12 507 reference individuals were contributed by 5 diagnostic laboratories.

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