Publications of Saskia BULK
Bookmark and Share    
See detailPreconceptional carrier screening in Belgium
BULK, Saskia ULiege; Lumaka Zola, Aimé ULiege

Conference (2019, November 22)

Detailed reference viewed: 22 (1 ULiège)
Full Text
See detailCOL1A2 mutation in a case of isolated short stature
HARVENGT, Julie ULiege; Boros, E.; BULK, Saskia ULiege et al

Poster (2019, March 15)

Detailed reference viewed: 28 (5 ULiège)
Full Text
See detailL'heterotopie nodulaire periventriculaire. Un cas pediatrique.
Ebetiuc, Iula ULiege; BULK, Saskia ULiege; LEROY, Patricia ULiege

in Revue medicale de Liege (2019), 74(7-8), 388-390

Periventricular nodular heterotopia (PVNH) is a cerebral cortex malformation, due to a deletion/duplication in the FLNA gene, located on the chromosome X. The gene is coding a cytoskeleton protein. The ... [more ▼]

Periventricular nodular heterotopia (PVNH) is a cerebral cortex malformation, due to a deletion/duplication in the FLNA gene, located on the chromosome X. The gene is coding a cytoskeleton protein. The transmission is dominant. It enters the heterogeneous group of philaminopathies. There is a feminine predominance. Males most often show early lethality. The clinical presentation is characterised by a seizure disorder ranging from mild to intractable, a mental retardation, hypotonia, cardiovascular abnormalities, vasculopathy and/or coagulopathy leading to stroke. The surveillance must be made by a pluridisciplinary team and the genetic counseling is necessary. We present here a paediatric case. [less ▲]

Detailed reference viewed: 26 (3 ULiège)
Full Text
See detailAberrant regulation of epigenetic modifiers contributes to the pathogenesis in patients with selenoprotein N-related myopathies
Bachmann, C.; Noreen, F.; Voermans, N. C. et al

in Human Mutation (2019)

Congenital myopathies are early onset, slowly progressive neuromuscular disorders of variable severity. They are genetically and phenotypically heterogeneous and caused by pathogenic variants in several ... [more ▼]

Congenital myopathies are early onset, slowly progressive neuromuscular disorders of variable severity. They are genetically and phenotypically heterogeneous and caused by pathogenic variants in several genes. Multi-minicore Disease, one of the more common congenital myopathies, is frequently caused by recessive variants in either SELENON, encoding the endoplasmic reticulum glycoprotein selenoprotein N or RYR1, encoding a protein involved in calcium homeostasis and excitation–contraction coupling. The mechanism by which recessive SELENON variants cause Multiminicore disease (MmD) is unclear. Here, we extensively investigated muscle physiological, biochemical and epigenetic modifications, including DNA methylation, histone modification, and noncoding RNA expression, to understand the pathomechanism of MmD. We identified biochemical changes that are common in patients harboring recessive RYR1 and SELENON variants, including depletion of transcripts encoding proteins involved in skeletal muscle calcium homeostasis, increased levels of Class II histone deacetylases (HDACs) and DNA methyltransferases. CpG methylation analysis of genomic DNA of patients with RYR1 and SELENON variants identified >3,500 common aberrantly methylated genes, many of which are involved in calcium signaling. These results provide the proof of concept for the potential use of drugs targeting HDACs and DNA methyltransferases to treat patients with specific forms of congenital myopathies. © 2019 Wiley Periodicals, Inc. [less ▲]

Detailed reference viewed: 15 (0 ULiège)
Full Text
See detailPanel-Based Exome Sequencing for Neuromuscular Disorders as a Diagnostic Service.
Westra, Dineke; Schouten, Meyke I.; Stunnenberg, Bas C. et al

in Journal of neuromuscular diseases (2019), 6(2), 241-258

BACKGROUND: Neuromuscular disorders (NMDs) are clinically and genetically heterogeneous. Accurate molecular genetic diagnosis can improve clinical management, provides appropriate genetic counseling and ... [more ▼]

BACKGROUND: Neuromuscular disorders (NMDs) are clinically and genetically heterogeneous. Accurate molecular genetic diagnosis can improve clinical management, provides appropriate genetic counseling and testing of relatives, and allows potential therapeutic trials. OBJECTIVE: To establish the clinical utility of panel-based whole exome sequencing (WES) in NMDs in a population with children and adults with various neuromuscular symptoms. METHODS: Clinical exome sequencing, followed by diagnostic interpretation of variants in genes associated with NMDs, was performed in a cohort of 396 patients suspected of having a genetic cause with a variable age of onset, neuromuscular phenotype, and inheritance pattern. Many had previously undergone targeted gene testing without results. RESULTS: Disease-causing variants were identified in 75/396 patients (19%), with variants in the three COL6-genes (COL6A1, COL6A2 and COL6A3) as the most common cause of the identified muscle disorder, followed by variants in the RYR1 gene. Together, these four genes account for almost 25% of cases in whom a definite genetic cause was identified. Furthermore, likely pathogenic variants and/or variants of uncertain significance were identified in 95 of the patients (24%), in whom functional and/or segregation analysis should be used to confirm or reject the pathogenicity. In 18% of the cases with a disease-causing variant of which we received additional clinical information, we identified a genetic cause in genes of which the associated phenotypes did not match that of the patients. Hence, the advantage of panel-based WES is its unbiased approach. CONCLUSION: Whole exome sequencing, followed by filtering for NMD genes, offers an unbiased approach for the genetic diagnostics of NMD patients. This approach could be used as a first-tier test in neuromuscular disorders with a high suspicion of a genetic cause. With uncertain results, functional testing and segregation analysis are needed to complete the evidence. [less ▲]

Detailed reference viewed: 15 (1 ULiège)
Full Text
See detailPhenotype-genotype correlation in children with neurofibromatosis type 1
BARREA, Christophe ULiege; VAESSEN, Sandrine ULiege; BULK, Saskia ULiege et al

in Neuropediatrics (2018)

Detailed reference viewed: 200 (10 ULiège)
Full Text
See detailEhlers-Danlos syndrome in the University Hospital of Liege
KUKOR, Léna ULiege; BERTOLI, Sabrina ULiege; Bours, Vincent ULiege et al

Poster (2018, February 16)

Detailed reference viewed: 149 (19 ULiège)
Full Text
See detailBiallelic B3GALT6 mutations cause spondylodysplastic Ehlers-Danlos syndrome.
Van Damme, Tim; Pang, Xiaomeng; Guillemyn, Brecht et al

in Human Molecular Genetics (2018), 27(20), 3475-3487

Proteoglycans are among the most abundant and structurally complex biomacromolecules and play critical roles in connective tissues. They are composed of a core protein onto which glycosaminoglycan (GAG ... [more ▼]

Proteoglycans are among the most abundant and structurally complex biomacromolecules and play critical roles in connective tissues. They are composed of a core protein onto which glycosaminoglycan (GAG) side chains are attached via a linker region. Biallelic mutations in B3GALT6, encoding one of the linker region glycosyltransferases, are known to cause either spondyloepimetaphyseal dysplasia (SEMD) or a severe pleiotropic form of Ehlers-Danlos syndromes (EDS). This study provides clinical, molecular and biochemical data on 12 patients with biallelic B3GALT6 mutations. Notably, all patients have features of both EDS and SEMD. In addition, some patients have severe and potential life-threatening complications such as aortic dilatation and aneurysm, cervical spine instability and respiratory insufficiency. Whole-exome sequencing, next generation panel sequencing and direct sequencing identified biallelic B3GALT6 mutations in all patients. We show that these mutations reduce the amount of beta3GalT6 protein and lead to a complete loss of galactosyltransferase activity. In turn, this leads to deficient GAG synthesis, and ultrastructural abnormalities in collagen fibril organization. In conclusion, this study redefines the phenotype associated with B3GALT6 mutations on the basis of clinical, molecular and biochemical data in 12 patients, and provides an in-depth assessment of beta3GalT6 activity and GAG synthesis to better understand this rare condition. [less ▲]

Detailed reference viewed: 27 (3 ULiège)
Full Text
See detailThe BElgian PREnatal MicroArray (BEMAPRE) database: A systematic nationwide repository of fetal genomic aberrations.
Muys, Joke; Blaumeiser, Bettina; Jacquemyn, Yves et al

in Prenatal Diagnosis (2018)

OBJECTIVE: With the replacement of karyotyping by chromosomal microarray (CMA) in invasive prenatal diagnosis, new challenges have arisen. By building a national database, we standardize the ... [more ▼]

OBJECTIVE: With the replacement of karyotyping by chromosomal microarray (CMA) in invasive prenatal diagnosis, new challenges have arisen. By building a national database, we standardize the classification and reporting of prenatally detected copy number variants (CNVs) across Belgian genetic centers. This database, which will link genetic and ultrasound findings with postnatal development, forms a unique resource to investigate the pathogenicity of variants of uncertain significance and to refine the phenotypic spectrum of pathogenic and susceptibility CNVs. METHODS: The BElgian PREnatal MicroArray (BEMAPRE) consortium is a collaboration of all genetic centers in Belgium. We collected data from all invasive prenatal procedures performed between May 2013 and July 2016. RESULTS: In this three-year period, 13266 prenatal CMAs were performed. By national agreement, a limited number of susceptibility CNVs and no variants of uncertain significance were reported. Added values for using CMA versus conventional karyotyping were 1.8% in the general invasive population and 2.7% in cases with an ultrasound anomaly. Of the reported CNVs 31.5% would have remained undetected with NIPT as the first-tier test. CONCLUSION: The establishment of a national database for prenatal CNV data allows for a uniform reporting policy and the investigation of the prenatal and postnatal genotype-phenotype correlation. [less ▲]

Detailed reference viewed: 39 (4 ULiège)
Full Text
See detailDysmorphology Quiz
BULK, Saskia ULiege; PIERQUIN, Geneviève ULiege

Conference (2016, February 04)

Detailed reference viewed: 64 (2 ULiège)
Full Text
See detailMicrodélétions et duplications 22q11.22 distales
PIERQUIN, Geneviève ULiege; CABERG, Jean-Hubert ULiege; BULK, Saskia ULiege

Poster (2016, February 03)

Detailed reference viewed: 20 (5 ULiège)
Full Text
See detailLe syndrome de Marfan chez l'enfant et l'adolescent : cas clinique
Magotteaux, S.; BULK, Saskia ULiege; FARHAT, Nesrine ULiege et al

in Revue Médicale de Liège (2016), 71(7-8), 342-348

Detailed reference viewed: 114 (6 ULiège)
Full Text
See detailA new case of microdeletion 14q32.3
Uwineza, Annette ULiege; BULK, Saskia ULiege; CABERG, Jean-Hubert ULiege et al

Poster (2015, March 06)

Detailed reference viewed: 47 (10 ULiège)
Full Text
See detailA tale of two anomalies. A paternal duplication and a maternal deletion of 15q13
BULK, Saskia ULiege; Decortis, Thierry ULiege; Rondia, G et al

Poster (2015, March 06)

Detailed reference viewed: 22 (3 ULiège)