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Biomedical subjects

J J Engelen

Publications and source records attributed to J J Engelen.

At least 19 recordsLinked to original sources
PubMed2000

Duplication of chromosome region 8p23.1-->p23.3: a benign variant?

Chromosome analysis was performed in a 34-year-old man who was phenotypically normal except for oligoasthenozoospermia. In this patient, analysis of GTG-banded chromosomes showed in one chromosome 8 additional chromosomal material of unknown origin. To characterize the aberrant chromosome more precisely, a paint specific for chromosome region 8pter-->8p23.1 was generated by microdissection and degenerated oligonucleotide primed-polymerase chain reaction (DOP-PCR) and used as fluorescence in situ hybridization (FISH) paint. After reverse painting, hybridization signals were only found on the short arm of the two chromosomes 8, with an enlarged signal on the derivative chromosome 8. The duplication was characterized further with band-specific FISH probes. We concluded that (part of) chromosome region 8p23.1-->p23.3 was duplicated. Chromosome analysis of the parents showed that the dup(8) was of maternal origin and that the fertile brother of the index patient also was a carrier of the chromosome aberration. There was no history of miscarriages. We suggest that duplication of region 8p23.1-->p23.3 can be regarded as euchromatic variant or duplication with no phenotypic effect.

Adult↗
PubMed2000

Prenatally detected marker chromosome identified as an i(22)(p10) using (micro)FISH.

MicroFISH was used to elucidate the chromosomal origin of a prenatally detected marker chromosome. Five copies of the marker chromosome were collected from GTG-banded metaphases and amplified by means of DOP-PCR. The PCR product was labeled with blotine-14-dATP and used as a FISH probe for hybridization to metaphase chromosomes of the fetus (reverse painting). The marker appeared to be derived from the short arm of (an) acrocentric chromosome(s). After FISH with centromere-specific and band-specific probes complete characterization was possible and the marker chromosome appeared to consist of two short arms of chromosome 22. The pregnancy was continued and one year after birth the patient is developing normal.

Chromosome Inversion↗
PubMed1999

Analysis of oxidative DNA damage and HPRT mutant frequencies in cancer patients before and after radiotherapy.

Various markers of radiation-induced DNA damage including DNA oxidation were investigated in peripheral lymphocytes of 23 cancer patients prior to and one week after receiving radiotherapy with a cumulative dose of 54-70 Gy. Exposure to ionizing radiation nonsignificantly increased the ratio 2'deoxy-7-dihydro-8-oxoguanosine/2'deoxyguanosine (8-oxodG/dG) from 1.73 x 10(-5) to 3.33 x 10(-5). Frequencies of micronuclei significantly (p = 0.0003) increased from 6.4 to 38.9 per 1000 cells. The frequency of hypoxanthine-guanine-phosphoribosyltransferase (HPRT) mutant lymphocytes measured as 6-thioguanine resistant variant cells by 5-bromodeoxyuridine labeling, was elevated eight-fold, from 4.7 x 10(-6) to 36.2 x 10(-6) (p = 0.008) after termination of the radiotherapy, thus showing a clear response to the radiation treatment. No correlation between levels of oxidative DNA damage and frequencies of HPRT mutant lymphocytes or micronuclei could be established.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

Detection of a cryptic translocation t(13;20)(q34;p13) in an unexplained case of MCA/MR: value of FISH over high resolution banding.

Cryptic unbalanced chromosome rearrangements in the telomeric bands of the chromosomes may constitute a significant cause of unexplained mental retardation with or without congenital anomalies. We report on a boy with a terminal deletion of the long arm of chromosome 13, combined with a partial duplication of the short arm of chromosome 20, owing to a cryptic balanced translocation in his father. The karyotype of the father was 46XY,t(13;20)(q34;p13). The propositus presented with severe mental and growth retardation, microcephaly, facial anomalies including ptosis of the right upper eyelid, a high nasal bridge, small palpebral fissures, and bilateral epicanthus, hypospadias, and scoliosis. A younger brother died at birth and had a low birth weight, hypospadias, and a horseshoe kidney. Repeated chromosome analyses with high resolution banding in the propositus and his parents were apparently normal. Chromosome painting eventually disclosed the cryptic translocation in the father with unbalanced karyotype in the propositus. The importance of additional FISH analysis in patients with unexplained mental retardation, physical anomalies, and apparently normal chromosomes is emphasized.

Abnormalities, Multiple↗
PubMed1999

Duplication within chromosome region 15q11-q13 in a patient with similarities to Prader-Willi syndrome confirmed by region-specific and band-specific fish.

We report on a patient presenting with mental retardation and obesity and a proximal duplication of chromosome 15. The patient shared some clinical signs with Prader-Willi syndrome. With a region-specific paint, generated by microdissection, a duplication in region 15q11.2-q13 was shown to be present. Subsequently, FISH with probes localized to chromosome region 15q11.2-q12 and microsatellite analysis was used to characterize this chromosome aberration further and an insertion duplication within the region frequently deleted in Prader-Willi and Angelman syndrome was demonstrated.

Child↗
PubMed1999

Characterization of a partial trisomy 16q with FISH. Report of a patient and review of the literature.

Characterization of a partial trisomy 16 q with FISH: Report of a patient and literature review: We report on a 28-year-old male patient with severe growth and mental retardation, severe behavioural problems, especially automutilation, and a spastic quadriplegia. He showed no specific dysmorphism. The karyotype was 46, XY, dir dup(16) (q11.2-q13). The clinical and cytogenetical findings are compared with 3 previously reported cases with proximal duplication 16q.

Adult↗
PubMed1998

Characterization of a de novo unbalanced translocation t(14q18q) using microdissection and fluorescence in situ hybridization.

We report on a patient with a de novo translocation between the long arms of chromosomes 14 and 18. The translocation was studied using microdissection in combination with fluorescence in situ hybridization (micro-FISH). Five copies of the chromosomes involved in the translocation were isolated by microdissection and amplified by means of degenerate oligonucleotide primed-polymerase chain reaction (DOP-PCR). Reverse chromosome painting with the biotin-labeled PCR product showed that part of the q-arm of chromosome 18 had no signal. The deletion was characterized further by FISH with band-specific probes and it was concluded that the rearrangement was unbalanced: 46,XY,t(14;18)(14pter-->14q22::18q21.1-->18qter) (18pter-->18q12.2::14q22-->14qter). The patient, who presented with psychomotor retardation, mild obesity, pes equinovarus, strabismus, and facial anomalies, is compared with previously reported patients with an interstitial deletion of band 18q12.

Child, Preschool↗
PubMed1998

A simple and efficient method for microdissection and microFISH.

A simple and efficient method for the dissection of (marker) chromosomes, (micro)nuclei, and chromosome regions is presented. Before microdissection, metaphases are overlaid with milli-Q water to rehydrate the chromosomes, which makes them soft and sticky. The dissected chromosome fragments are dissolved without proteinase-K or topoisomerase treatment and directly amplified using a degenerate oligonucleotide primed polymerase chain reaction (DOP-PCR). The advantages of this microFISH method over previously reported methods are: (1) microdissection in this way is very fast; (2) a chromosome, marker, (micro)nucleus, or chromosome region is collected as a whole using only one microneedle; (3) the dissected material sticks tightly to the needle without the risk of getting lost; (4) no Sequenase is used in the DOP-PCR reaction which reduces the risk of contamination.

Humans↗
PubMed1998

Two cases of partial trisomy 8p and partial monosomy 21q in a family with a reciprocal translocation (8;21)(p21.1;q22.3).

We report on two mentally retarded adults with an unbalanced karyotype resulting from a familial balanced translocation between chromosomes 8 and 21, t(8;21)(p21.1;q22.3). This translocation has not been reported before. Both patients had partial trisomy 8p and partial monosomy 21q. Fluorescence in situ hybridisation (FISH) was used to determine the chromosomal breakpoints more precisely. The first patient showed mild mental retardation and facial dysmorphism, slightly resembling the earlier described trisomy 8p phenotype. He did not resemble his affected niece, who was more severely retarded, had serious epilepsy, but lacked the facial dysmorphism. Comparing the data of both patients with published reports of trisomy 8p, marked differences were found between patients with an inversion duplication (inv dup) 8p, patients with partial trisomy 8p caused by an unbalanced translocation, and our patients. Inv dup(8p) causes a recognisable phenotype, whereas the phenotype of trisomy 8p resulting from a translocation is much more variable, probably because of the accompanying monosomies. However, even the same abnormal karyotype can cause different phenotypes, as our patients show. Counselling carriers of the balanced translocation in this family, a 20-25% recurrence risk for unbalanced offspring and a 25% risk for miscarriages seem appropriate.

Adult↗
PubMed1998

Strong variable clinical presentation in 3 patients with 7q terminal deletion.

We report 3 patients with a 7q terminal deletion. The first, a 7 weeks old female, with a de novo 7q36-->qter deletion, was microcephalic and had a partial hypoplasia of the corpus callosum on the MRI-scan of the brain. The second, a 3 months old male, showed microcephaly, disproportionate growth retardation, truncal obesity and facial dysmorfism giving the clinical impression of a "microcephalic primordial dwarfism (osteodysplastic type)". At the age of 6 months he had developed a single maxillary central incisor suggesting a minimal form of holoprosencephaly (HPE). Additional FISH-studies showed a 7q36.1-->qter deletion, as the unbalanced product of a t(5;7)(q35.2;q36.1)pat. The de novo 7q36-->qter deletion in the third patient, a 5 years old female, was associated with borderline intelligence, mild microcephaly, small midface, choanal narrowing and a single maxillary central incisor as a minimal form of HPE. CT- and MRI-scan of the brain were normal. In these 3 patients extensive FISH analysis was performed to investigate the possible involvement of the HPE gene region on chromosome 7q36. The target gene for HPE, the Sonic hedgehog gene (SHH) as well as several other genes important for normal brain development (En2;HOX1,HTR5A) were found to be deleted in all three patients. Our findings stress the importance of 7q36 microdeletion studies in patients with even minimal signs of HPE, as relative microcephaly with small midface (choanal narrowing), agenesis/hypoplasia of the corpus callosum/septum pellucidum, thalamic fusion or a single maxillary central incisor.

Abnormalities, Multiple↗
PubMed1998

Oxidative DNA damage and cytogenetic effects in flight engineers exposed to cosmic radiation.

This study set out to analyze biomarkers for genotoxic events, e.g., oxidative DNA damage, chromosomal damage and hprt mutations, among flight personnel, who are known to be occupationally exposed to ionizing radiation of cosmic origin. Twenty-three flight engineers were recruited while ground personnel served as a matched control group. Cumulative radiation doses during flight were calculated on the basis of subjects' flight records assuming an exposure rate of 6 microSv per hour of flight. Oxidative DNA damage in peripheral lymphocytes from flight engineers appeared significantly increased in comparison with controls and was associated with cumulative exposure to cosmic radiation. Frequencies of peripheral lymphocyte chromosome aberrations, micronuclei and hprt mutations appeared also to be increased in flight engineers, but not significantly. It was also observed that DNA damage was higher in flight engineers with a relatively shorter flight history in comparison with flight engineers with higher cumulative exposures to radiation, suggesting adaptation to DNA damage caused by ionizing radiation. DNA repair activities measured as unscheduled DNA synthesis were clearly increased in the higher-exposed subgroup of flight engineers, and appeared significantly correlated with cumulative radiation dose, as well as inversely with oxidative DNA damage. The implications for cancer risk assessment in relation to exposure to cosmic radiation are discussed.

Aerospace Medicine↗
PubMed1997

Severe feeding problems and congenital laryngostenosis in a patient with 3q23 deletion.

UNLABELLED: Common clinical features of patients with 3q23 deletion include the phenotype of BPES (blepharophimosis, ptosis, epicanthus inversus and telecanthus syndrome), growth and mental retardation, microcephaly ear and nose dysmorphism and joint and digit abnormalities. We report on a 3-year-old girl with the phenotype of BPES, mental retardation, facial dysmorphism and camptodactyly. In addition, she had a congenitally small larynx and severe, chronic feeding difficulties. Chromosome studies revealed an interstitial deletion in the long arm of chromosome 3: del(3)(q23-q25). CONCLUSION: Congenital laryngostenosis and severe feeding problems may be part of the clinical syndrome caused by chromosome 3q23 deletion.

Abnormalities, Multiple↗
PubMed1996

Deletion of the long arm of chromosome 6: two new patients and literature review.

Two children with a partial monosomy 6q are reported: a girl with an interstitial deletion [46,XX,del(6)(q16.2q23.1)], and a boy with a terminal deletion [46,XY,del(6)(q25.1)]. Both children presented with developmental delay, facial dysmorphism and a cardiac defect. The patients have been studied using G banding and cosmid probes specific for the long arm of chromosome 6. Clinical data are compared with patients reported in the literature.

Abnormalities, Multiple↗
PubMed1996

Marker chromosome identification by micro-FISH.

Micro-FISH was used to elucidate the chromosomal origin of marker chromosomes in three patients. Ten copies of marker chromosomes were collected with microneedles from GTG banded metaphases, transferred to a collecting drop and amplified by means of DOP-PCR. The PCR products were labeled with biotin-14-dATP and used as FISH probes for hybridization to normal metaphase chromosomes and to metaphase chromosomes of the patients (reverse painting). With the generation of chromosome region-specific painting probes by PCR amplification of microdissected DNA and subsequent FISH it was possible to identify the marker chromosomes in all patients. One marker appeared to be derived from the centromere region of the X-chromosome and the proximal third of the long arm, one from the centromere region of chromosome 17 and one marker chromosome was identified as an isochromosome 18p.

Adult↗
PubMed1996

Disclosure of five breakpoints in a complex chromosome rearrangement by microdissection and FISH.

Microdissection and fluorescence in situ hybridisation (FISH) were used to elucidate the nature of a complex chromosome translocation, after GTG banding failed in the complete characterisation of the structural rearrangement between chromosomes 6 and 12. These chromosomes were painted with chromosome specific paints and one of the chromosome regions involved in the translocation was isolated by microdissection. Ten copies of the microdissected region were collected with microneedles from GTG banded metaphases, transferred to a collecting drop, and amplified by means of DOP-PCR. The PCR product was labelled with biotin-14-dATP and used as a FISH probe for hybridisation to normal metaphase chromosomes and metaphase chromosomes of the patients (microFISH). FISH with this chromosome region specific painting probe and with chromosome band specific probes enabled the characterisation of a complex chromosome rearrangement with five breakpoints in two chromosomes. This resulted in the following karyotype: 46,XY,t(6;12)(6pter--> 6q12::12q24.1-->12qter;12qter-->12q13.3:: 6q16.2-->6q26::12q13.3-->12q24.1::6q12--> 6q16.2::6q26-->6qter).

Adolescent↗