References of "SEGERS, Karin"
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See detail3-years experience review of neonatal screening for hemoglobin disorders using tandem mass spectrometry.
BOEMER, François ULg; Cornet, Yves ULg; LIBIOULLE, Cécile ULg et al

in Clinica Chimica Acta (2011), 412(15-16), 1476-9

BACKGROUND: Neonatal screening programs for sickle cell disease are common in North America and in some European countries. Isoelectric Focusing or High Performance Liquid Chromatography is the main ... [more ▼]

BACKGROUND: Neonatal screening programs for sickle cell disease are common in North America and in some European countries. Isoelectric Focusing or High Performance Liquid Chromatography is the main technique used for hemoglobin variant detection. METHODS: Since tandem mass spectrometry is being used for screening of inherited metabolic disorders and allows protein identification, we had developed an application to identify the most relevant hemoglobin mutations with this technology. RESULTS: This approach had been previously validated and has been routinely applied in our laboratory for the last three years. We report here our experience with this new method in the field, applied to our East-Belgian population. CONCLUSIONS: To conclude, mass spectrometry provides an efficient alternative approach for laboratories performing neonatal screening of hemoglobin disorders. [less ▲]

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See detailFree sialic acid storage disease mimicking cerebral palsy and revealed by blood smear examination.
Debray, François-Guillaume ULg; Lefebvre, Caroline ULg; Colinet, Stephanie et al

in Journal of Pediatrics (2011), 158(1), 1651651

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See detailImproved molecular diagnostics of idiopathic short stature and allied disorders: quantitative polymerase chain reaction-based copy number profiling of SHOX and pseudoautosomal region 1.
D'haene, Barbara; Hellemans, Jan; Craen, Margarita et al

in Journal of Clinical Endocrinology and Metabolism (2010), 95(6), 3010-8

CONTEXT: Short stature has an incidence of three in 100 in children. Reliable molecular genetic testing may be crucial in the context of beneficial disease management. Deletions spanning or surrounding ... [more ▼]

CONTEXT: Short stature has an incidence of three in 100 in children. Reliable molecular genetic testing may be crucial in the context of beneficial disease management. Deletions spanning or surrounding the SHOX gene account for a significant proportion of patients with idiopathic short stature (ISS) and allied disorders, such as Leri-Weill dyschondrosteosis. OBJECTIVE: Several shortcomings of current strategies for copy number profiling of the SHOX region prompted us to develop an improved test for molecular diagnostics of the SHOX region. DESIGN AND RESULTS: We introduced a quantitative PCR (qPCR)-based copy number profiling test, consisting of 11 amplicons targeting clinically relevant regions, i.e. the SHOX gene and regulatory regions. To ensure an optimal sensitivity and specificity, this test was validated in 32 controls and 18 probands with previously identified copy number changes. In addition, 152 probands with SHOX-associated phenotypes were screened, revealing 10 novel copy number changes. CONCLUSION: This highly validated qPCR test supersedes other approaches for copy number screening of the SHOX region in terms of reliability, accuracy, and cost efficiency. In addition, another strong point is the fact that it can be easily implemented in any standard equipped molecular laboratory. Our qPCR-based test is highly recommended for molecular diagnostics of idiopathic short stature and allied disorders. [less ▲]

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See detailGenetic Analysis of Rwandan Patients With Cystic Fibrosis-Like Symptoms: Identification of Novel Cystic Fibrosis Transmembrane Conductance Regulator and Epithelial Sodium Channel Gene Variants.
Mutesa, Léon; Azad, Abul Kalam; Verhaeghe, Catherine ULg et al

in CHEST (2009), 135(5), 1233-42

Background The defect in chloride and sodium transport in cystic fibrosis (CF) patients is a consequence of CFTR loss of function and of an abnormal interaction between CFTR and ENaC. A few patients were ... [more ▼]

Background The defect in chloride and sodium transport in cystic fibrosis (CF) patients is a consequence of CFTR loss of function and of an abnormal interaction between CFTR and ENaC. A few patients were described with CF-like symptoms, a single CFTR mutation and an ENaC mutation. Methods To study African patients with CF-like symptoms and to relate the disease to gene mutations of both CFTR and ENaC genes, we collected clinical data and DNA samples from 60 African patients with a CF phenotype. The CFTR gene was first analyzed in all patients by dHPLC followed by direct sequencing, whereas the SCNN1A, SCNN1B and SCNN1G subunits of ENaC gene were analyzed by sequencing in the five patients who carried only one CF mutation. The frequency of all identified ENaC variants was established in a control group of 200 healthy individuals and in the 55 CF-like patients without any CFTR mutation Results Three CFTR mutants, including one previously undescribed missense mutation (p.A204T), and a 5T/7T variant were identified in five patients. ENaC gene sequencing in these 5 patients detected 8 ENaC variants: c.72T>C and p.V573I in SCNN1A; p.V348M, p.G442V, c.1473 + 28C>T, and p.T577T in SCNN1B; and p.S212S, c.1176 + 30G>C in SCNN1G. In the 55 CF-like patients without any CFTR mutation, we identified five of these eight ENaC variants, including the frequent p.G442V polymorphism, but we did not detect the presence of the p.V348M, p.T577T, and c.1176 + 30G>C ENaC variants. Moreover, these last three ENaC variants, p.V348M, p.T577T, and c.1176 + 30G>C, were not found in the control group. Conclusion Our data suggest that CF-like syndrome in Africa could be associated with CFTR and ENaC mutations. [less ▲]

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See detailDeletion of Xpter encompassing the SHOX gene and PAR1 region in familial patients with Leri-Weill Dyschondrosteosis syndrome.
Mutesa, L.; Vanbellinghen, Jean-François ULg; Hellin, Anne-Cécile ULg et al

in Genetic Counseling (Geneva, Switzerland) (2009), 20(1), 9-17

Heterozygote deletions or mutations of pseudoautosomal 1 region (PAR1) encompassing the short stature homeobox-containing (SHOX) gene cause Leri-Weill Dyschondrosteosis (LWD), which is a dominantly ... [more ▼]

Heterozygote deletions or mutations of pseudoautosomal 1 region (PAR1) encompassing the short stature homeobox-containing (SHOX) gene cause Leri-Weill Dyschondrosteosis (LWD), which is a dominantly inherited osteochondroplasia characterized by short stature with mesomelic shortening of the upper and lower limbs and Madelung deformity of the wrists. SHOX is expressed by both sex chromosomes in males and females and plays an important role in bone growth and development. Clinically, the LWD expression is variable and more severe in females than males due to sex differences in oestrogen levels. Here, we report two familial cases of LWD with a large Xp terminal deletion (approximately 943 kb) of distal PAR1 encompassing the SHOX gene. In addition, the proband had mental retardation which appeared to be from recessive inheritance in the family. [less ▲]

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See detailNovel SACS mutation in a Belgian family with sacsin-related ataxia.
Ouyang, Y.; SEGERS, Karin ULg; BOUQUIAUX, Olivier ULg et al

in Journal of the Neurological Sciences (2008), 264(1-2), 73-6

The authors describe the four patients in the first known Belgian family with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). A novel homozygous missense mutation, NM_014363.3: c.3491T ... [more ▼]

The authors describe the four patients in the first known Belgian family with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). A novel homozygous missense mutation, NM_014363.3: c.3491T>A in exon 9, of the SACS gene was identified in the present family, which results in an original amino acid of methionine to lysine substitution at amino acid residue 1164 (p.M1164K). Although the cardinal clinical features, i.e., spastic ataxia with peripheral neuropathy, in our patients were similar to those in Quebec patients, our patients exhibited some atypical clinical features, e.g., teenage-onset and absence of retinal hypermyelination. The present family is from Wallonia, and there could be shared ethnicity with the families of Charlevoix-Saguenay. [less ▲]

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See detailGermline PTPN11 missense mutation in a case of Noonan syndrome associated with mediastinal and retroperitoneal neuroblastic tumors.
Mutesa, Léon; Pierquin, Geneviève ULg; Janin, Nicolas ULg et al

in Cancer Genetics & Cytogenetics (2008), 182(1), 40-2

Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, typical craniofacial dysmorphism, skeletal anomalies, congenital heart defects, and predisposition to malignant ... [more ▼]

Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, typical craniofacial dysmorphism, skeletal anomalies, congenital heart defects, and predisposition to malignant tumors. In approximately 50% of cases, the disease is caused by missense mutations in the PTPN11 gene. To date, solid tumors, and particularly brain tumors and rhabdomyosarcomas, have been documented in patients with NS; however, few cases of neuroblastoma associated with NS have been reported. Here we report an unusual case of neuroblastoma with mediastinal, retroperitoneal, and medullar locations associated in a NS patient carrying a PTPN11 germline missense mutation (p.G60A). This missense mutation occurs within the N-SH2 domain of the PTPN11 gene and has been reported to be associated with acute leukemia in NS patients. The association of this p.G60A PTPN11 mutation with neuroblastoma provides new evidence that gain of function PTPN11 mutations may play an important role in the pathogenesis of solid tumors associated with Noonan syndrome. [less ▲]

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See detailSpinocerebellar ataxia type 2 (SCA2): clinical features and genetic analysis.
Mutesa, Leon; Pierquin, Geneviève ULg; Segers, Karin ULg et al

in Journal of Tropical Pediatrics (2008), 54(5), 350-2

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease that results from the expansion of an unstable trinucleotide CAG repeat encoding for a polyglutamine tract. In ... [more ▼]

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease that results from the expansion of an unstable trinucleotide CAG repeat encoding for a polyglutamine tract. In normal individuals, alleles contain between 14 and 31 CAG repeats, whereas the pathological alleles have more than 35 CAG repeats. The clinical phenotype of SCA2 includes a progressive cerebellar ataxia with additional features such as ophthalmoplegia, extra-pyramidal or pyramidal signs and peripheral neuropathy. We report a SCA2 large African family with several affected individuals. A major pathological allele carrying 43 CAG repeats was identified in the proband. To our knowledge, this is a first report of a SCA disorder described in Central African patients, thus indicating the need to consider this diagnosis in young African ataxic patients. [less ▲]

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See detailThe callipyge mutation and other genes that affect muscle hypertrophy in sheep.
Cockett, Noelle E; Smit, Maria A; Bidwell, Christopher A et al

in Genetics, Selection, Evolution (2005), 37 Suppl 1

Genetic strategies to improve the profitability of sheep operations have generally focused on traits for reproduction. However, natural mutations exist in sheep that affect muscle growth and development ... [more ▼]

Genetic strategies to improve the profitability of sheep operations have generally focused on traits for reproduction. However, natural mutations exist in sheep that affect muscle growth and development, and the exploitation of these mutations in breeding strategies has the potential to significantly improve lamb-meat quality. The best-documented mutation for muscle development in sheep is callipyge (CLPG), which causes a postnatal muscle hypertrophy that is localized to the pelvic limbs and loin. Enhanced skeletal muscle growth is also observed in animals with the Carwell (or rib-eye muscling) mutation, and a double-muscling phenotype has been documented for animals of the Texel sheep breed. However, the actual mutations responsible for these muscular hypertrophy phenotypes in sheep have yet to be identified, and further characterization of the genetic basis for these phenotypes will provide insight into the biological control of muscle growth and body composition. [less ▲]

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See detailMosaicism of Solid Gold supports the causality of a noncoding A-to-G transition in the determinism of the callipyge phenotype.
Smit, Maria; SEGERS, Karin ULg; Carrascosa, Laura Garcia et al

in Genetics (2003), 163(1), 453-6

To identify the callipyge mutation, we have resequenced 184 kb spanning the DLK1-, GTL2-, PEG11-, and MEG8-imprinted domain and have identified an A-to-G transition in a highly conserved dodecamer motif ... [more ▼]

To identify the callipyge mutation, we have resequenced 184 kb spanning the DLK1-, GTL2-, PEG11-, and MEG8-imprinted domain and have identified an A-to-G transition in a highly conserved dodecamer motif between DLK1 and GTL2. This was the only difference found between the callipyge (CLPG) allele and a phylogenetically closely related wild-type allele. We report that this SNP is in perfect association with the callipyge genotype. The demonstration that Solid Gold-the alleged founder ram of the callipyge flock-is mosaic for this SNP virtually proves the causality of this SNP in the determinism of the callipyge phenotype. [less ▲]

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See detailComparative sequence analysis of the imprinted Dlk1-Gtl2 locus in three mammalian species reveals highly conserved genomic elements and refines comparison with the Igf2-H19 region.
Paulsen, M.; Takada, S.; Youngson, N. A. et al

in Genome Research (2001), 11(12), 2085-94

The Dlk1-Gtl2 domain on mouse chromosome 12 contains reciprocally imprinted genes with the potential to contribute to our understanding of common features involved in imprinting control. We have sequenced ... [more ▼]

The Dlk1-Gtl2 domain on mouse chromosome 12 contains reciprocally imprinted genes with the potential to contribute to our understanding of common features involved in imprinting control. We have sequenced this conserved region in the mouse and sheep and included the human sequence in a three species comparison. This analysis resulted in a precise conservation map and identification of highly conserved sequence elements, some of which we have shown previously to be differentially methylated in the mouse. Additionally, this analysis facilitated identification of a CpG-rich tandem repeat array located approximately 13-15 kb upstream of Gtl2. Furthermore, we have identified a third imprinted transcript that overlaps with the last Dlk1 exon in the mouse. This transcript lacks a conserved open reading frame and is probably generated by cleavage of extended Dlk1 transcripts. Because Dlk1 and Gtl2 share many of the imprinting properties of the well-characterized Igf2-H19 domain, it has been proposed that the two regions may be regulated in the same way. Comparative genomic examination of the two domains indicates that although there are similarities, other features are very different, including the location of conserved CTCF-binding sites, and the level of conservation at regulatory regions. [less ▲]

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See detailBreakpoint mapping positions the callipyge gene within a 450-kilobase chromosome segment containing the DLK1 and GTL2 genes.
Berghmans, S.; SEGERS, Karin ULg; Shay, T. et al

in Mammalian Genome : Official Journal of the International Mammalian Genome Society (2001), 12(2), 183-5

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See detailFine-mapping and construction of a bovine contig spanning the ovine callipyge locus.
Shay, T. L.; Berghmans, S.; SEGERS, Karin ULg et al

in Mammalian Genome : Official Journal of the International Mammalian Genome Society (2001), 12(2), 141-9

The callipyge (CLPG) gene was fine-mapped by linkage analysis to a 4.6-cM chromosome interval on distal ovine OAR18q, flanked by microsatellite markers IDVGA30 and OY3. The OAR18q linkage map and human ... [more ▼]

The callipyge (CLPG) gene was fine-mapped by linkage analysis to a 4.6-cM chromosome interval on distal ovine OAR18q, flanked by microsatellite markers IDVGA30 and OY3. The OAR18q linkage map and human HSA14q transcript map were aligned by genotyping two bovine-hamster whole-genome radiation hybrid panels with the microsatellite markers, as well as with sequences corresponding to HSA 14q genes. Using Type I loci mapping to the IDVGA30-OY3 interval as anchor points, we have constructed a 1.4-Mb bovine BAC contig containing the IDVGA30-OY3 interval. We demonstrate that the IDVGA30-OY3 interval spans approximately 770 kb and contains at least four genes: YY1, WARS, DLK1, and GTL2. [less ▲]

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See detailConstruction and characterization of an ovine BAC contig spanning the callipyge locus.
SEGERS, Karin ULg; Vaiman, D.; Berghmans, S. et al

in Animal Genetics (2000), 31(6), 352-9

We describe the construction of an ovine BAC contig spanning a 4.6 centimorgan (cM) chromosome segment known to contain the callipyge (CLPG) locus. The contig comprises 21 ovine BAC clones jointly ... [more ▼]

We describe the construction of an ovine BAC contig spanning a 4.6 centimorgan (cM) chromosome segment known to contain the callipyge (CLPG) locus. The contig comprises 21 ovine BAC clones jointly covering approximately 900 kilobases (Kb). Two gaps in the BAC contig, spanning 10 and 7.5 Kb, respectively, were bridged by long range PCR. The corresponding chromosome region was shown to be characterized by an unusually low Kb to cM ratio (164 Kb/cM) and a high density of Not1 sites (1:126 Kb) possibly reflecting a high gene density in the corresponding chromosome region. Equivalent amplification of 64 sequence tagged sites spanning the corresponding region from homozygous +/+ and CLPG/CLPG individuals disproves the hypothesis of a major deletion causing the CLPG mutation. [less ▲]

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