Publications by authors named "Ilse J Anderson"

7 Publications

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Variants in TCF20 in neurodevelopmental disability: description of 27 new patients and review of literature.

Genet Med 2019 09 11;21(9):2036-2042. Epub 2019 Feb 11.

Spectrum Health Medical Genetics, Grand Rapids, MI, USA.

Purpose: To define the clinical characteristics of patients with variants in TCF20, we describe 27 patients, 26 of whom were identified via exome sequencing. We compare detailed clinical data with 17 previously reported patients.

Methods: Patients were ascertained through molecular testing laboratories performing exome sequencing (and other testing) with orthogonal confirmation; collaborating referring clinicians provided detailed clinical information.

Results: The cohort of 27 patients all had novel variants, and ranged in age from 2 to 68 years. All had developmental delay/intellectual disability. Autism spectrum disorders/autistic features were reported in 69%, attention disorders or hyperactivity in 67%, craniofacial features (no recognizable facial gestalt) in 67%, structural brain anomalies in 24%, and seizures in 12%. Additional features affecting various organ systems were described in 93%. In a majority of patients, we did not observe previously reported findings of postnatal overgrowth or craniosynostosis, in comparison with earlier reports.

Conclusion: We provide valuable data regarding the prognosis and clinical manifestations of patients with variants in TCF20.
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http://dx.doi.org/10.1038/s41436-019-0454-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171701PMC
September 2019

De novo variants in FBXO11 cause a syndromic form of intellectual disability with behavioral problems and dysmorphisms.

Eur J Hum Genet 2019 05 24;27(5):738-746. Epub 2019 Jan 24.

Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.

Determining pathogenicity of genomic variation identified by next-generation sequencing techniques can be supported by recurrent disruptive variants in the same gene in phenotypically similar individuals. However, interpretation of novel variants in a specific gene in individuals with mild-moderate intellectual disability (ID) without recognizable syndromic features can be challenging and reverse phenotyping is often required. We describe 24 individuals with a de novo disease-causing variant in, or partial deletion of, the F-box only protein 11 gene (FBXO11, also known as VIT1 and PRMT9). FBXO11 is part of the SCF (SKP1-cullin-F-box) complex, a multi-protein E3 ubiquitin-ligase complex catalyzing the ubiquitination of proteins destined for proteasomal degradation. Twenty-two variants were identified by next-generation sequencing, comprising 2 in-frame deletions, 11 missense variants, 1 canonical splice site variant, and 8 nonsense or frameshift variants leading to a truncated protein or degraded transcript. The remaining two variants were identified by array-comparative genomic hybridization and consisted of a partial deletion of FBXO11. All individuals had borderline to severe ID and behavioral problems (autism spectrum disorder, attention-deficit/hyperactivity disorder, anxiety, aggression) were observed in most of them. The most relevant common facial features included a thin upper lip and a broad prominent space between the paramedian peaks of the upper lip. Other features were hypotonia and hyperlaxity of the joints. We show that de novo variants in FBXO11 cause a syndromic form of ID. The current series show the power of reverse phenotyping in the interpretation of novel genetic variances in individuals who initially did not appear to have a clear recognizable phenotype.
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http://dx.doi.org/10.1038/s41431-018-0292-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462006PMC
May 2019

CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language.

Nat Commun 2018 11 5;9(1):4619. Epub 2018 Nov 5.

AP-HP, Hôpital de la Pitié-Salpêtrière, Département de Génétique, Paris, 75013, France.

Chromatin remodeling is of crucial importance during brain development. Pathogenic alterations of several chromatin remodeling ATPases have been implicated in neurodevelopmental disorders. We describe an index case with a de novo missense mutation in CHD3, identified during whole genome sequencing of a cohort of children with rare speech disorders. To gain a comprehensive view of features associated with disruption of this gene, we use a genotype-driven approach, collecting and characterizing 35 individuals with de novo CHD3 mutations and overlapping phenotypes. Most mutations cluster within the ATPase/helicase domain of the encoded protein. Modeling their impact on the three-dimensional structure demonstrates disturbance of critical binding and interaction motifs. Experimental assays with six of the identified mutations show that a subset directly affects ATPase activity, and all but one yield alterations in chromatin remodeling. We implicate de novo CHD3 mutations in a syndrome characterized by intellectual disability, macrocephaly, and impaired speech and language.
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http://dx.doi.org/10.1038/s41467-018-06014-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218476PMC
November 2018

De novo variants in are associated with hypotonia, developmental delay, intellectual disability, and autism.

Cold Spring Harb Mol Case Stud 2017 Nov 21;3(6). Epub 2017 Nov 21.

Department of Pediatrics, Columbia University Medical Center, New York, New York 10032, USA.

Using whole-exome sequencing, we identified seven unrelated individuals with global developmental delay, hypotonia, dysmorphic facial features, and an increased frequency of short stature, ataxia, and autism with de novo heterozygous frameshift, nonsense, splice, and missense variants in the () gene. EBF3 is a member of the collier/olfactory-1/early B-cell factor (COE) family of proteins, which are required for central nervous system (CNS) development. COE proteins are highly evolutionarily conserved and regulate neuronal specification, migration, axon guidance, and dendritogenesis during development and are essential for maintaining neuronal identity in adult neurons. Haploinsufficiency of may affect brain development and function, resulting in developmental delay, intellectual disability, and behavioral differences observed in individuals with a deleterious variant in .
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http://dx.doi.org/10.1101/mcs.a002097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701309PMC
November 2017

New directions in cytogenetic and molecular testing of the neonate.

Semin Perinatol 2005 Jun;29(3):144-9

Department of Medical Genetics, University of Tennessee Graduate School of Medicine, Knoxville, TN 37920, USA.

The development of new diagnostic, and hence therapeutic possibilities, has brought the realization that genetic disease is now an integral part of medical practice. Advances in cytogenetic and molecular testing have drastically improved the ability to diagnose with certainty many previously unrecognized conditions. However, this advance in technology does not come without new questions. New tests are not always the most cost effective ones, some have significant diagnostic limitations, and others raise valid ethical issues surrounding the testing of minors. A working understanding of new advances in genetic diagnosis as well as their inherent limitations is crucial for the contemporary practitioner.
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http://dx.doi.org/10.1053/j.semperi.2004.12.001DOI Listing
June 2005
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