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L Messiaen

Publications and source records attributed to L Messiaen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Identification of BPESC1, a novel gene disrupted by a balanced chromosomal translocation, t(3;4)(q23;p15.2), in a patient with BPES.

The blepharophimosis syndrome (BPES) is a rare genetic disorder characterized by blepharophimosis, ptosis, epicanthus inversus, and telecanthus. In type I, BPES is associated with female infertility, while in type II, the eyelid defect occurs by itself. The BPES syndrome has been mapped to 3q23. Previously, we constructed a YAC-, PAC-, and cosmid-based physical map surrounding the 3q23 translocation breakpoint of a t(3;4)(q23;p15.2) BPES patient, containing a 110-kb PAC (169-C 10) and a 43-kb cosmid (11-L 10) spanning the breakpoint. In this report, we present the identification of BPESC1 (BPES candidate 1), a novel candidate gene that is disrupted by the translocation on chromosome 3. Cloning of the cDNA has been performed starting from a testis-specific EST, AI032396, found in cosmid 11-L 10. The cDNA sequence of BPESC1 is 3518 bp in size and contains an open reading frame of 351 bp. No significant similarities with known proteins have been found in the sequence databases. BPESC1 contains three exons and spans a genomic fragment of 17.5 kb. Expression of BPESC1 was observed in adult testis tissue. We performed mutation analysis in 28 unrelated familial and sporadic BPES patients, but, apart from the disruption by the translocation, found no other disease-causing mutations. These data make it unlikely that BPESC1 plays a major role in the pathogenesis of BPES.

Adult↗
PubMed2000

arg-cys substitution at codon 1246 of the human myosin Va gene is not associated with Griscelli syndrome.

Myosin Va is an actin-associated motor protein involved in organelle transport such as melanosomes and neuron synaptic vesicles and has always been proposed as the candidate gene for the autosomal recessive Griscelli-Pruniéras syndrome, one of the silvery hair syndromes, which is a lethal disease combining immunodeficiency and neurologic and pigmentary abnormalities. Thus far, two mutations in the myosin Va gene have been described to be associated with this syndrome. One of these mutations was a homozygous mis-sense mutation causing an arginine to cysteine alteration at codon 1246. Because we also found this particular substitution after mutation analysis of a Griscelli patient, we checked its relevance in a control group of 124 unrelated healthy individuals and found it to be present, even in homozygous state, in normal unaffected individuals. It is clear that this arg1246cys substitution is a polymorphism occurring in the human population and not occurring in association with Griscelli syndrome. Distinguishing a polymorphism from a bona fide mutation is of utmost importance and has major ethical implications with regard to prenatal genetic counseling in affected families.

Albinism↗
PubMed2000

Occurrence of scleroderma in monozygotic twins.

Familial occurrence of scleroderma is rare and concordance for the disease in twins has been reported exceptionally. We describe 2 female identical twin pairs concordant for scleroderma. The first twin pair was diagnosed with the systemic form of scleroderma, the second pair with the localized form.

Child↗
PubMed1999

Closing in on the BPES gene on 3q23: mapping of a de Novo reciprocal translocation t(3;4)(q23;p15.2) breakpoint within a 45-kb cosmid and mapping of three candidate genes, RBP1, RBP2, and beta'-COP, distal to the breakpoint.

BPES is a genetic disorder presenting with blepharophimosis, ptosis of the eyelids, epicanthus inversus, and telecanthus. BPES type I is associated with female infertility, whereas type II presents without additional symptoms. Hitherto, it remains unknown whether BPES type I results from a defect in a single gene or from a contiguous gene syndrome. Previous cytogenetic and linkage analyses have assigned a BPES locus to 3q23, in a 5-cM interval between D3S1615 and D3S1316. In this report, we describe the molecular and physical characterization of the 3q23 breakpoint in a BPES patient with a t(3;4)(q23;p15.2) translocation. Eight YACs located around and within the D3S1615-D3S1316 interval were mapped relative to the 3q23 breakpoint; 5 YACs spanning the 3q23 breakpoint were identified. Thirteen STSs and ESTs were localized on the YAC map. Subsequent hybridization of 2 YACs spanning the breakpoint to the Human RPCI1 PAC Library and the Human Chromosome 3 LLNL Cosmid Library resulted in the identification of 12 PACs and 50 cosmids respectively, allowing the construction of a detailed PAC and cosmid physical map. A refined position-telomeric to the breakpoint-of 3 candidate genes, cellular retinol-binding proteins 1 and 2 (RBP1, RBP2) and the coatomer beta' subunit (beta'-COP), was obtained on this physical map. Furthermore, a PAC and cosmid contig encompassing the breakpoint was constructed. PAC 169-C 10 and cosmid 11-L 10 crossing the breakpoint have sizes of 110 and 45 kb, respectively. The isolation of coding sequences in these clones and in the rest of the contig will greatly facilitate further efforts toward positional cloning of the gene(s) involved in BPES.

Blepharophimosis↗
PubMed1999

Mutation analysis of the BRCA1 and BRCA2 genes results in the identification of novel and recurrent mutations in 6/16 flemish families with breast and/or ovarian cancer but not in 12 sporadic patients with early-onset disease. Mutations in brief no. 224. Online.

Since the identification of the BRCA1 and BRCA2 genes (MIM#s 113705 and 600185), more than hundred different mutations throughout both genes have been reported. Recurrent mutations are rare and mainly due to founder effects. We analyzed 12 sporadic female patients with breast cancer before age 35, as well as 16 unrelated families, presenting with either (i) at least 3 first degree relatives with breast and/or ovarian cancer diagnosed at any age, or (ii) at least 2 first and/or second degree relatives with breast and/or ovarian cancer before age 45 years. We performed a protein truncation test for BRCA1 exon 11 and BRCA2 exons 10 and 11 and heteroduplex analysis for all the remaining exons of BRCA1 and 2. Presence of genomic deletions encompassing exons 13 or 22 of BRCA1, known to be Dutch founder mutations, was investigated by PCR. In 6/16 (37.5%) unrelated families the causal mutation in either the BRCA1 or BRCA2 gene was identified. Four different mutations were found in the BRCA1 gene: IVS5+3A>G (intron 5), 1191delC (exon 11), R1443X (exon 13), IVS22+5G>A (intron 22) and two in the BRCA2 gene: 6503delTT (exon 11), 6831delTG (exon 11). 1191delC (BRCA1) and 6831delTG (BRCA2) are novel mutations. IVS5+3A>G in exon 5 of BRCA1 published by Peelen et al. (1997) as a novel Belgian mutation, was identified in one additional family, not fulfilling our inclusion criteria. In the group of 12 sporadic female patients no mutations were found.

Adult↗
PubMed1999

Preimplantation genetic diagnosis of Marfan syndrome with the use of fluorescent polymerase chain reaction and the Automated Laser Fluorescence DNA Sequencer.

OBJECTIVE: To develop and apply clinical preimplantation genetic diagnosis (PGD) for Marfan syndrome. DESIGN: Case report. SETTING: Centers for medical genetics and reproductive medicine in university hospitals. PATIENT(S): One couple in which the husband was affected with Marfan syndrome. INTERVENTION(S): The couple underwent three intracytoplasmic sperm injection cycles. MAIN OUTCOME MEASURE(S): The correct diagnosis was obtained for embryos in three PGD cycles. RESULT(S): Although all the PGD cycles were followed by ET, no pregnancy ensued. CONCLUSION(S): This assay can provide a reliable and accurate preimplantation diagnosis of Marfan syndrome.

Adult↗
PubMed1999

Mutation analysis of the BRCA1 and BRCA2 genes in the Belgian patient population and identification of a Belgian founder mutation BRCA1 IVS5 + 3A > G.

Since the identification of the BRCA1 and BRCA2 genes, several hundred different germline mutations in both genes have been reported. Recurrent mutations are rare and mainly due to founder effects. As the mutational spectrum of the BRCA1 and BRCA2 genes in the Belgian patient population is largely unknown, we initiated mutation analysis for the complete coding sequence of both genes in Belgian families with multiple breast and/or ovarian cancer patients and in "sporadic" patients with early onset disease. We completed the analysis in 49 families and in 19 "sporadic" female patients with early onset breast and/or ovarian cancer. In 15 families we identified a mutation (12 mutations in BRCA1 and 3 mutations in BRCA2). In 5 apparently unrelated families the same splice site mutation was identified (BRCA1 IVS5 + 3A > G). Haplotype analysis revealed a common haplotype immediately flanking the mutation in all families suggesting that disease alleles are identical by descent. In none of the 19 sporadic patients was a mutation found.

Adult↗
PubMed1999

Genetic counselling and testing for hereditary breast and ovarian cancer: the gent(le) approach.

The counselling experience with 50 Flemish families in whom mutation analysis of the total coding region of the BRCA1 and BRCA2 gene has been initiated, is presented. Genetic testing for breast-ovarian cancer susceptibility is offered by a multidisciplinary team. During the counselling sessions, special attention is given to comprehensible and emotionally acceptable communication of genetic information and to the psychosocial evaluation of the counselee. The limitations of molecular testing and the controversy surrounding cancer prevention strategies are also discussed. The overall acceptance of mutation testing is high. Some of the problems encountered are inaccuracy of the reported family history, poor retrieval of the medical records of affected family members and the reluctance of many patients to inform their relatives about the possibility of being tested.

Adult↗
PubMed1998

Human myosin V gene produces different transcripts in a cell type-specific manner.

In mice, tissue-specific alternative splicing of the myosin V gene in the C-terminal tail domain is well documented with exclusion of exon F from brain transcripts, but present in skin, particularly in melanocytes. As alternative splicing of the myosin V C-terminal tail domain in human tissues is undocumented, we studied the presence of myosin V splice forms in different types of human cultured normal skin cells, i.e., dermal fibroblasts, melanocytes, and keratinocytes as well as in human blood leukocytes, using an RT-PCR-based method. In all cell types studied, several different length transcripts were present containing different exon combinations, including exon F. This is the first report showing the presence of exon F as well as alternative splicing in the human myosin V tail domain. As the full-length transcript is most abundant in melanocytes and leukocytes and both cell types are involved in Griscelli syndrome, a tissue-specific role of this particular transcript needs further investigation.

Alternative Splicing↗
PubMed1998

Prenatal diagnosis of a constitutional interstitial deletion of chromosome 5 (q15q31.1) presenting with features of congenital contractural arachnodactyly.

Prenatal diagnosis of a constitutional interstitial deletion of chromosome 5 (q15q31.1) in a 30-year-old woman is reported. At 21 weeks of pregnancy, routine fetal ultrasounds showed the presence of apparently isolated bilateral club feet. Fetal karyotyping documented an interstitial deletion of the long arm of chromosome 5: 46,XX,del(5) (q15q31) in all 50 analyzed metaphases. Because such deletion is associated with severe psychomotor retardation, the pregnancy was terminated. Postmortem karyotyping of skin fibroblasts confirmed the presence of this interstitial de novo deletion in all mitoses. The breakpoints on 5q were analyzed by fluorescent in situ hybridization and were localized at 5q15 and q31.1. This case illustrates the importance of fetal karyotyping in cases of isolated club feet. At autopsy, the fetus presented had minor anomalies and contractures of knee and hip joints. These clinical findings could fit the diagnosis of congenital contractural arachnodactyly (CCA) or Beals syndrome. CCA is caused by a defect in the fibrillin-2 (FBN2) gene. This gene was previously mapped on 5q23-31. Our molecular studies of both parents and the fetus, using an intragenic polymorphic GT repeat, showed that the FBN2 gene was deleted in the fetus and that the de novo interstitial deletion occurred on the paternally inherited chromosome 5. Thus, CCA may be caused by a loss of function of the FBN2 gene. Clinical findings in this fetus and those of other described cases with interstitial 5q deletions are reviewed, and similarities with CCA are stressed.

Abnormalities, Multiple↗
PubMed1998

Molecular analysis of 1p36 breakpoints in two Merkel cell carcinomas.

Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine tumor of the skin. Only little information is available on the genetic alterations occurring in this tumor. Cytogenetic studies thus far have not shown recurrent chromosomal changes, although various structural chromosome 1 rearrangements, including deletions, often leading to loss of distal 1p material appear to be frequent. We report on fluorescence in situ hybridization and loss of heterozygosity analyses of an MCC tumor and MCC cell line UISO. The present study has shown that two distinct regions in the most distal band 1p36 on the short arm of chromosome 1 can be implicated in MCC. One region at 1p36.3 was delineated by a distal deletion in the MCC tumor as a result of an unbalanced translocation, resulting in loss of all markers distal to ENO1. This region was previously shown to be deleted in different tumor types including neuroblastoma. In cell line UISO an insertion in 1p36.2 was identified. The insertion breakpoint indicates a second, more proximal, region on 1p involved in MCC. The insertion breakpoint was mapped within a cluster of repetitive tRNA and snRNA genes and thus could coincide with the constitutional 1p36 breakpoint previously reported in a patient with neuroblastoma.

Aged↗
PubMed1998

Noonan-like phenotype in monozygotic twins with a duplication-deficiency of the long arm of chromosome 18 resulting from a maternal paracentric inversion.

We report on newborn monozygotic twins with a Noonan-like phenotype, and multiple congenital anomalies due to a monocentric recombinant chromosome 18. The mother carried a paracentric inversion of the long arm of chromosome 18, inv(18)(q21.1q22.3). Cytogenetic, fluorescent in situ hybridization, comparative genomic hybridization and DNA marker analyses allowed the delineation of the deleted (18q22.3-qter) and duplicated (18q12.1-q21.1) chromosomal regions in the recombinant chromosome 18, and suggest that this duplication-deletion chromosome 18 resulted from breakage of a dicentric recombinant chromosome 18 with subsequent reconstitution of telomeric sequences on the long arm. Marked variability is observed in the phenotypic expression of the same chromosomal anomaly in these monozygotic twins. The clinical findings of these patients are compared with those reported in proximal 18q-duplication and distal 18q-deletion patients. The clinical features of both infants are compatible with Noonan syndrome, suggesting that a locus for this syndrome may be located on the long arm of chromosome 18.

Chromosome Deletion↗
PubMed1998

Application of fluorescence in situ hybridization to the identification of different marker chromosomes.

Chromosome studies performed on lymphocyte culture of a baby with specific dysmorphism and congenital anomalies suggestive of trisomy 21 revealed a mosaicism: 46,XY,rea(21q21q) [25]/47,XY,rea(21q21q),+mar1[25]. The karyotype of the mother is normal, but the father's karyotype presents an supernumerary chromosome greater and different from the marker of his son: 47,XY,+mar2 (100%). The identification of the two marker chromosomes by standard cytogenetic techniques followed by molecular techniques is essential for the identification of the origin of these two chromosomes. The unusual presence of two different markers one in the father and one in the son, as well as the clinical features of the child, are presented. The possible role of the paternal marker, in the de novo chromosomal rearrangement in his child will be discussed.

Abnormalities, Multiple↗
PubMed1997

Interstitial deletion 2q33.3-q34 in a boy with a phenotype resembling the Seckel syndrome.

A boy presented at 5 weeks with a syndrome of pre- and postnatal growth retardation, microcephaly, muscular hypotonia, and facial anomalies resembling those seen in Seckel syndrome or microcephalic primordial dwarfism I. Analysis of prometaphase chromosomes, fluorescent in situ hybridization (FISH), and molecular studies showed the presence of a de novo chromosome 2 deletion that could be defined as del(2)(q33.3q34)pat. Parental chromosomes were normal, except for the presence of a paternal supernumerary marker identified by FISH as der(15). On follow-up of the patient during the next months length development appeared normal and the diagnosis of Seckel syndrome was withdrawn. Clinical findings of previously published cases with interstitial deletion of at least 2q33.3-q34, the deletion present in the propositus, are reviewed and include pre- and postnatal growth retardation, psychomotor retardation, microcephaly, micrognathia, and abnormal/low-set ears; findings also present in the propositus. These findings resemble those described in the Seckel syndrome. Noteworthy is the finding that 2/3 of the 60 reviewed cases originally reported as having Seckel syndrome apparently belong to a heterogeneous group of low birth weight microcephalic dwarfism I yet to be clearly defined. In these patients no chromosome 2q deletion has been reported so far. Retrospective analysis could show if a subgroup of these patients carry submicroscopic deletions at 2q33.3-q34. Alternatively, molecular analysis of this region may be warranted in newly diagnosed patients with Seckel syndrome-like manifestations.

Abnormalities, Multiple↗