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S P Romana

Publications and source records attributed to S P Romana.

At least 19 recordsLinked to original sources
PubMed2006

NUP98 rearrangements in hematopoietic malignancies: a study of the Groupe Francophone de Cytogénétique Hématologique.

The NUP98 gene is fused with 19 different partner genes in various human hematopoietic malignancies. In order to gain additional clinico-hematological data and to identify new partners of NUP98, the Groupe Francophone de Cytogénétique Hématologique (GFCH) collected cases of hematological malignancies where a 11p15 rearrangement was detected. Fluorescence in situ hybridization (FISH) analysis showed that 35% of these patients (23/66) carried a rearrangement of the NUP98 locus. Genes of the HOXA cluster and the nuclear-receptor set domain (NSD) genes were frequently fused to NUP98, mainly in de novo myeloid malignancies whereas the DDX10 and TOP1 genes were equally rearranged in de novo and in therapy-related myeloid proliferations. Involvement of ADD3 and C6ORF80 genes were detected, respectively, in myeloid disorders and in T-cell acute lymphoblastic leukemia (T-ALL), whereas the RAP1GDS1 gene was fused to NUP98 in T-ALL. Three new chromosomal breakpoints: 3q22.1, 7p15 (in a localization distinct from the HOXA locus) and Xq28 were detected in rearrangements with the NUP98 gene locus. The present study as well as a review of the 73 cases previously reported in the literature allowed us to delineate some chromosomal, clinical and molecular features of patients carrying a NUP98 gene rearrangements.

Adolescent↗
PubMed2005

[Microarray CGH: principle and use for constitutional disorders].

Chips technology has allowed to miniaturize process making possible to realize in one step and using the same device a lot of chemical reactions. The application of this technology to molecular cytogenetics resulted in the development of comparative genomic hybridization (CGH) on microarrays technique. Using this technique it is possible to detect very small genetic imbalances anywhere in the genome. Its usefulness has been well documented in cancer and more recently in constitutional disorders. In particular it has been used to detect interstitial and subtelomeric submicroscopic imbalances, to characterize their size at the molecular level or to define the breakpoints of translocation. The challenge today is to transfer this technology in laboratory medicine. Nevertheless this technology remains expensive and the existence of numerous sequence polymorphisms makes its interpretation difficult. Finally its is unlikely that it will make karyotyping obsolete as it does not allow to detect balanced rearrangements which after meiotic segregation might result in genome imbalance in the progeny.

Child↗
PubMed2005

Molecular cytogenetic analysis of five 2q37 deletions: refining the brachydactyly candidate region.

Deletions of the 2q37 region are associated with a recognizable pattern of MCA/MR so-called the AHO-like syndrome. Brachydactyly is a variable but characteristic feature of this clinical entity. Here we report on five cases of cytogenetically visible de novo deletions of this 2q37 chromosome region. Using FISH, we characterized at the molecular level the breakpoints of these deletions using a set of 15 BACs, PACs and YACs. In four patients, terminal deletions of variable size ranged between 6.2 and 10 Mb. The fifth patient had an interstitial deletion with an AHO-like phenotype including brachydactyly. These findings when compared to previous observations allowed us to narrow down the brachydactyly critical region between BACs RP11-585E12 and RP11-351E10. It contains HDAC4 and STK25 candidate genes loci.

Adult↗
PubMed2003

PMX2B, a new candidate gene for Hirschsprung's disease.

Hirschsprung's (HSCR) disease is a congenital intestinal malformation of the enteric nervous system. It is a multigenic malformation and until now, eight genes have been involved in the etiology of this disease: genes encoding proteins of the RET signaling pathway (RET, GDNF and NTN), genes participating in the endothelin (EDN) type B receptor pathway (EDNRB, EDN3 and ECE-1), the SOX10 gene and the SIP1 gene that is mutated in syndromic forms of HSCR. Mutations of these genes are found in not more than 50-60% of affected individuals. Here, we report on the results of a molecular cytogenetic study performed in a girl who presented with a syndromic short segment HSCR associated with a de novo t(4;8)(p13;p22) translocation. A comparative genomic hybridization (CGH) study found a 4p12p13 deletion. A molecular characterization of this rearrangement showed that the 4p13 deletion was 5 Mb in length and included the paired mesoderm homeobox gene (PMX2B) (MIM 603851), a gene expressed in the human embryonic gut and essential for the development of autonomic neural crest derivatives. The present observation suggests that PMX2B haploinsuffciency might predispose to HSCR.

Abnormalities, Multiple↗
PubMed2002

Molecular characterization of partial trisomy 16q24.1-qter: clinical report and review of the literature.

We describe a 3(1/2)-year-old girl with psychomotor and mental retardation; dysmorphic features, including a high forehead with bitemporal narrowing; a broad nasal bridge and a broadened nose; downslanting palpebral fissures; abnormal ears; vertebral abnormalities; cardiac defect; genital hypoplasia; and anal abnormalities. The karyotype of our patient (550 bands) was normal. Molecular cytogenetic techniques, including comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH), revealed that this girl was a carrier of a de novo derivative chromosome 7 arising from a cryptic t(7;16)(p22.3;q24.1) translocation generating a trisomy 16q24.1-qter and a 7p22.3-pter deletion. FISH with a series of specific chromosome 7p and 16q probes allowed us to delineate the chromosome 7 breakpoint between YAC660G6 (WD7S517) and YAC848A12 (D7S521, D7S31, and WI-4829) and the chromosome 16 breakpoint between BAC457K7 (D42053) and BAC44201 (SGC30711). The comparison of the clinical features of our patient with those of 2 cases of pure terminal 7p deletion and 28 cases of trisomy 16q reported in the literature allowed us to establish the following phenotype-genotype correlation for trisomy of the long arm of chromosome 16: distinctive facies (high/prominent forehead, bitemporal narrowing, periorbital edema in the neonatal period); severe mental retardation; vertebral, genital, and anal abnormalities to 16q24; distal joint contractures and camptodactyly to 16q23; cleft palate and renal anomalies to 16q22; beaked nose and gall bladder agenesis to 16q21; gut malrotation; lung and liver anomalies to 16q13; and behavior abnormalities to band 16q11-q13.

Abnormalities, Multiple↗
PubMed2002

A CGH study of 27 patients with CHARGE association.

CHARGE association is a non-random occurrence of congenital malformations including coloboma, heart disease, choanal atresia, retarded growth and/or retarded development, genital hypoplasia, ear anomalies and/or deafness. The cause of this association remains unknown. Various genetic mechanisms have been proposed, including a contiguous gene syndrome but, so far, no recurrent locus has been identified. To address this question, we decided to perform a comparative genomic hybridization (CGH) study on a cohort of 27 patients with CHARGE association and a normal standard karyotype. We found two chromosomal anomalies: a der(9)t(9;13) derived from a paternal translocation and a der(6)t(4;6) of unknown origin. This suggests that chromosome imbalances may well mimic CHARGE association. Therefore patients with CHARGE association must be carefully tested with classical and molecular cytogenetic techniques to detect a potential chromosome imbalance. It is expected that more stringent diagnostic criteria of CHARGE association could define a more homogeneous group of patients where a single genetic cause might be identified.

Abnormalities, Multiple↗
PubMed2001

Reassessment of childhood B-lineage lymphoblastic leukemia karyotypes using spectral analysis.

We studied a stratified cohort of 51 childhood B-lineage acute lymphoblastic leukemias (B-ALLs) to evaluate the efficiency of spectral karyotyping (SKY) in the detection of chromosome aberrations previously diagnosed using chromosome banding and/or reverse transcriptase polymerase chain reaction. Despite the small number of cases analyzed, several important features emerge from the study: (a) The result of banding analysis was revised in two-thirds of the cases. Eighty-three chromosome anomalies previously undetected or not characterized using chromosome banding were identified by spectral karyotyping, even in patients with apparently normal karyotypes. (b) All hyperdiploidy cases showed one or more extra copies of chromosomes X, 14, and 21. (c) Two hidden rearrangements, a t(7;12)(?p12;p13), and a new translocation, a t(9;12)(q31;p13), both involving the TEL gene, were characterized. (d) Some cryptic rearrangements, such as the der(21) t(12;21) translocation, remained undetected. (e) No new recurrent chromosome anomalies were discovered with this technique. In conclusion, the present study confirms the efficiency of the SKY technique in resolving and characterizing many complex chromosome anomalies seen in childhood B-ALLs, but it raises questions about the ability of this technique to detect cryptic rearrangements, such as the t(12;21) translocation.

Burkitt Lymphoma↗
PubMed2000

Subtle familial unbalanced translocation t(8;11)(p23.2;p15.5) in two fetuses with Beckwith-Wiedemann features.

We describe a subtle translocation t(8;11)(p23.2;p15.5) ascertained after two induced abortions in the same sibship because of the discovery of fetal hydrops on ultrasound examination. Initial cytogenetic studies performed on cultured amniotic fluid cells were considered as normal in both fetuses. High resolution banding analysis and FISH studies performed on the parents' chromosomes revealed a paternal translocation t(8;11)(p23.2;p15.5). Retrospective FISH analysis of both fetuses showed that they carried the same chromosomal imbalance including a distal monosomy 8pter and a distal trisomy 11pter. The phenotypes of the fetuses were re-examined and found to be compatible with Beckwith-Wiedemann syndromes (BWS). FISH analysis using an IGF2 probe demonstrated the presence of three copies of the IGF2 gene. This study highlights the value of searching for subtle chromosome rearrangements in families with recurrent unexplained multiple malformation syndromes discovered prenatally. Also, it contributes to a better delineation of the prenatal phenotype of BWS. Finally, it sheds new light on the aetiology of non-immune hydrops fetalis.

Adult↗
PubMed1997

The TEL gene products: nuclear phosphoproteins with DNA binding properties.

The human TEL gene is involved in several 12p13 chromosomal abnormalities present in various human hematological malignancies, the most frequent being the t(12;21)(p13;q22), specific for childhood acute lymphoblastic leukemia. The predicted product of TEL harbours an amino acid region similar to the ETS DNA binding domain. We now report the isolation of the murine TEL cDNA and the characterization of the human TEL proteins. Human and murine TEL proteins are particularly homologous within their aminoterminal regions and their ETS domains. TEL proteins are nuclear and display specific DNA binding activity toward classical ETS binding sites. In addition, we show that TEL mRNAs initiate translation at either of the two first inframe ATGs (codon 1 and 43) to encode 50 kDa and 57 kDa TEL proteins. In vivo, each of these primary translational products is modified by multiple phosphorylation events.

Animals↗
PubMed1996

Secondary acute myeloblastic leukemia with t(16;21) (q24;q22). involving the AML1 gene.

A t(16;21) (q24;122) translocation was detected by fluorescence in situ hybridization in a patient with acute myeloblastic leukemia previously treated for malignant lymphoma. While the breakpoint on chromosome 21 was within the AML1 gene as determined by FISH, the gene partner on chromosome 16 could not be identified. Band 16q24 appears to be rearranged in several types of myeloid proliferation and a review of the literature shows that these rearrangements most often occur in secondary leukemia and myelodysplastic syndrome or are part of complex chromosomal rearrangements.

Adult↗
PubMed1996

Molecular cytogenetics of t(12;21) (p13;q22).

The translocation t(12;21)(p13;q22) is a frequent nonrandom rearrangement of B-cell lineage childhood acute lymphoblastic leukemia (ALL) which fuses the TEL and AML1 genes, normally localized to 12p13 and 21q22, respectively. The crucial chimeric gene, TEL-AML1, is transcribed from the der(21) and encodes the 336 NH2 aminoacics of TEL fused to the majority of the AML1 protein. The t(12;21) is very often associated with loss of the normal, untranslocated TEL allele. These various aspects are presented here.

Burkitt Lymphoma↗
PubMed1996

Deletion of the short arm of chromosome 12 is a secondary event in acute lymphoblastic leukemia with t(12;21).

Translocation t(12;21) has been described as a nonrandom event in acute lymphoblastic leukemia (ALL) in patients with deletion of the short arm of chromosome 12, using fluorescence in situ hybridization techniques. Extensive FISH experiments were performed in order to re-examine the short arm of chromosome 12 in three children with ALL, previously shown to have t(12;21). It was shown that the t(12;21) is undetectable by routine R-banding technique and that the translocated 12 looks like a cytogenetically normal chromosome 12 in the three patients. Partial 12p deletion involving the TEL locus was shown to be interstitial in one patient with 12p- by using cosmid and YAC probes. In the second patient, the 12p- chromosome was secondary to the translocation since it was observed in about one half of the metaphases analyzed with FISH. In the third patient, the region of TEL usually rearranged in the t(12;21) displayed a germline pattern by Southern blotting, at diagnosis and in relapse. A few metaphases showed associated 12p- by standard cytogenetics, only in relapse. Thus we conclude that the TEL allele not involved in t(12;21) is inconstantly lost in patients with this subtype of ALL and occurs on the 12p- chromosome. These data question the status of tumor suppressor gene hypothesized for TEL.

Blotting, Southern↗
PubMed1995

High frequency of t(12;21) in childhood B-lineage acute lymphoblastic leukemia.

The recurrent t(12;21)(p12;q22) translocation fuses two genes, TEL and AML1, that have previously been shown to be independently involved in myeloid malignant proliferations. A search for rearrangement of the TEL locus in the region known to be involved in t(12;21) was performed by Southern blotting in a panel of hematopoietic malignancies. The presence of a t(12;21) was confirmed by fluorescence in situ hybridization (FISH) and/or reverse transcriptase (RT)-polymerase chain reaction (PCR). We report that fusion of TEL to AML1 is specifically observed in at least 16% of the childhood B-lineage acute lymphoblastic leukemia (ALL) investigated, none of which had been previously identified as harboring t(12;21).

Adolescent↗