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C D Delozier-Blanchet

Publications and source records attributed to C D Delozier-Blanchet.

At least 19 recordsLinked to original sources
PubMed2001

Axonemal beta heavy chain dynein DNAH9: cDNA sequence, genomic structure, and investigation of its role in primary ciliary dyskinesia.

Dyneins are multisubunit protein complexes that couple ATPase activity with conformational changes. They are involved in the cytoplasmatic movement of organelles (cytoplasmic dyneins) and the bending of cilia and flagella (axonemal dyneins). Here we present the first complete cDNA and genomic sequences of a human axonemal dynein beta heavy chain gene, DNAH9, which maps to 17p12. The 14-kb-long cDNA is divided into 69 exons spread over 390 kb. The cDNA sequence of DNAH9 was determined using a combination of methods including 5' rapid amplification of cDNA ends, RT-PCR, and cDNA library screening. RT-PCR using nasal epithelium and testis RNA revealed several alternatively spliced transcripts. The genomic structure was determined using three overlapping BACs sequenced by the Whitehead Institute/MIT Center for Genome Research. The predicted protein, of 4486 amino acids, is highly homologous to sea urchin axonemal beta heavy chain dyneins (67% identity). It consists of an N-terminal stem and a globular C-terminus containing the four P-loops that constitute the motor domain. Lack of proper ciliary and flagellar movement characterizes primary ciliary dyskinesia (PCD), a genetically heterogeneous autosomal recessive disorder with respiratory tract infections, bronchiectasis, male subfertility, and, in 50% of cases, situs inversus (Kartagener syndrome, KS). Dyneins are excellent candidate genes for PCD and KS because in over 50% of cases the ultrastructural defects of cilia are related to the dynein complex. Genotype analysis was performed in 31 PCD families with two or more affected siblings using a highly informative dinucleotide polymorphism located in intron 26 of DNAH9. Two families with concordant inheritance of DNAH9 alleles in affected individuals were observed. A mutation search was performed in these two "candidate families," but only polymorphic variants were found. In the absence of pathogenic mutations, the DNAH9 gene has been excluded as being responsible for autosomal recessive PCD in these families.

Adenosine Triphosphate↗
PubMed2000

Primary ciliary dyskinesia: a genome-wide linkage analysis reveals extensive locus heterogeneity.

Primary ciliary dyskinesia (PCD), or immotile cilia syndrome (ICS), is an autosomal recessive disorder affecting ciliary movement with an incidence of 1 in 20000-30000. Dysmotility to complete immotility of cilia results in a multisystem disease of variable severity with recurrent respiratory tract infections leading to bronchiectasis and male subfertility. Ultrastructural defects are present in ciliated mucosa and spermatozoa. Situs inversus (SI) is found in about half of the patients (Kartagener syndrome). We have collected samples from 61 European and North American families with PCD. A genome-wide linkage search was performed in 31 multiplex families (169 individuals including 70 affecteds) using 188 evenly spaced (19cM average interval) polymorphic markers. Both parametric (recessive model) and non-parametric (identity by descent allele sharing) linkage analyses were used. No major locus for the majority of the families was identified, although the sample was powerful enough to detect linkage if 40% of the families were linked to one locus. These results strongly suggest extensive locus heterogeneity. Potential genomic regions harbouring PCD loci were localised on chromosomes 3p, 4q, 5p, 7p, 8q, 10p, 11q, 13q, 15q, 16p, 17q and 19q. Linkage analysis using PCD families with a dynein arm deficiency provided 'suggestive' evidence for linkage to chromosomal regions 8q, 16pter, while analyses using only PCD families with situs inversus resulted in 'suggestive' scores for chromosomes 8q, and 19q.

Ciliary Motility Disorders↗
PubMed1998

Chromosome mapping of Rett syndrome: a likely candidate region on the telomere of Xq.

Rett syndrome (RS) is a disease of neurological development. First reported 30 years ago in 1966, its biological and genetic basis remains obscure. RS is commonly thought of as an X linked dominant disorder lethal to hemizygous males. The few familial cases would arise through mosaicism or because of occasional females failing to manifest the disorder through skewed X inactivation in relevant cell types. We have one family where the mother and daughter are affected with RS, and which can be explained according to this hypothesis. If the alternative proposal of Thomas (1996) is correct, that the lack of males affected by such disorders is the result of a high male to female ratio of germline mutations rather than of gestational lethality, then the RS gene should be located on the grandpaternal chromosome. Genomic screening with markers covering the whole X chromosome has been performed. Studies using multiple informative markers indicate that the RS locus is likely to be located close to one of the X chromosome telomeres. Further investigations in eight additional families suggest the most likely region for the RS gene to be is the distal part of Xq (Xq28).

Chromosome Mapping↗
PubMed1995

Trisomy 3 mosaicism on CVS: case report with literature review and propositions for investigation and counseling.

Chorionic villus sampling performed for advanced maternal age revealed trisomy 3 in 20% of mitoses studied after a semi-direct chromosomal harvest. Amniocytes and cord blood showed a non-mosaic 46,XY karyotype. The birthweight of the normal newborn was at the tenth percentile. Analysis of term placenta by cytogenetics and by fluorescent in situ hybridization (FISH) confirmed the presence of the trisomy 3 in 20% and 12%, respectively, of cells from two peripheral placental biopsies. Placental histology was heterogeneous, some portions showing immature, edematous and undervascularized villi. DNA analysis confirmed the biparental origin of the chromosomes 3 in the child, whose development is normal at 36 months.

Adult↗
PubMed1993

Cutaneous findings in ring chromosome 7 syndrome.

All 9 cases of ring chromosome 7 syndrome already identified had skin lesions: 7 had vascular lesions, 5 showed large pigmented congenital nevi, 3 had café-au-lait spots and in 1 case there were achromic spots on the trunk. One girl developed malignant melanoma at the age of 17 years. It appears that in patients presenting with growth retardation and pigmented skin lesions, with or without mental retardation, a cytogenetic study is indicated to search for ring chromosome 7, which is probably more frequent than suggested by the literature.

Chromosomes, Human, Pair 7↗
PubMed1993

Melanoma associated with ring chromosome 7.

We report the case of a 17-year-old girl with a constitutional chromosome anomaly (ring chromosome 7), associated with multiple pigmented skin lesions, who developed malignant melanoma. Eight other cases of ring chromosome 7 are described in the literature; all present vascular or pigmented skin lesions, but our patient was the first to develop a malignant tumor. Genetic studies in malignant melanoma are discussed, as well as the possible link between a constitutional anomaly of chromosome 7 and the occurrence of malignant melanoma. This association is possibly not fortuitous, particularly since most ring chromosome 7 patients reported to date have pigmented skin lesions.

Adolescent↗
PubMed1991

[Cytogenic anomalies and placental function].

Over the past few years growing knowledge of placental cytogenetics has led to the surprising observation that the chromosomal constitution of the placenta is not always identical to that of its fetus. This information comes primarily from three sources: analyses of chorionic villi obtained by choriocentesis (chorionic villus sampling); studies of abortions, particularly spontaneous ones; and analyses of extrafetal tissues performed following dubious prenatal diagnoses, or to investigate fetal pathologies such as intrauterine growth retardation. Our personal data and those reviewed in this article allow the conclusion that chromosomal aberrations, particularly in the mosaic state, are frequent in the placenta, and that at least some of these have less severe consequences when present in extrafetal tissues than when present in the fetus itself. The types of chromosomal errors observed differ according to the method of ascertainment, in spontaneous abortions for example as compared to pregnancies developing as far as the third trimester. The presence of a partially aneuploid placenta may be compatible with a continuing pregnancy, but be associated with problems such as inadequate fetal growth.

Abortion, Spontaneous↗
PubMed1989

[Microencephalic nanism, severe retardation, hypertonia, obesity, and hypogonadism in two brothers: a new syndrome?].

Two brothers are described with a severe syndrome of postnatal growth and mental retardation which includes extreme microcephaly, obesity developing during infancy, microgonadismsm, and a characteristic amphora-shaped facies. The neurological exam is highly abnormal, with hypertonia and hyperreflexia, nystagmus, and an extremely irritable and agitated behavior. The first child, who died at 4/1/2 years, also presented neonatal hypoglycemia and chronic constipation. Although the etiology of this syndrome is unknown, it is tempting to consider an X-linked recessive gene, given the importance of the X chromosome in mental retardation. Among the over 70 syndromes of X-linked mental retardation already described, our patients resemble individuals with the Börjeson-Forssman-Lehmann (BFL) syndrome the most. However, the severity of their dwarfism and mental retardation is much greater than described in any BFL patient to date, and the neurological and dysmorphic features vary significantly from those described in the BFL. Although a particularly severe variant, perhaps allelic, is a possibility, an as yet undescribed disorder is also plausible, the etiology of which would probably be recessive, either autosomal or X-linked.

Brain↗
PubMed1989

[Chorionic villus sampling (CVS): level of activity and methods to resolve certain difficulties in interpretation].

As of December 1, 1988, we had, as part of our prenatal diagnostic service, studied 458 transcervical chorionic villus biopsies. Three-fourths of these samples were taken because of advanced maternal age (greater than or equal to 35 years), whereas nearly one fifth were done to alleviate parental anxiety. The remainder were performed because of a precedent chromosomal anomaly in child or parent, to determine fetal sex in the case of X-linked familial disorders, or to obtain DNA for molecular analyses. Among the cytogenetic anomalies detected after 24 to 48 hours of culture, eight involved classical trisomies. In four other instances the chromosomal abnormalities were more difficult to interpret (mosaic trisomies 10, 13 and 15, an apparently uniform trisomy 7). All four were revealed to be "false positives", since neither the amniocenteses nor the karyotypes of the normal newborns (one pregnancy is still ongoing) confirmed an abnormal karyotype. In the case of the trisomy 7 we were able, after birth of the baby, to study two placental biopsies, one of which revealed an abnormality distinct from that detected in the chorionic villi. The observations concerning a fifth false positive are more worrisome, as an apparently uniform trisomy 18, with a fetus showing growth retardation on ultrasound, could not be confirmed in the abortus. Otherwise, we have not encountered a false negative result. In this article we discuss the mechanisms potentially responsible for the cytogenetic discrepancies sometimes observed between fetal and placental tissues. Molecular analyses may help to establish whether a chromosomal anomaly present in fetal chorionic villi had its origin in the pre- or post-zygotic stage; in the latter case the aneuploidy may be uniquely extrafetal.

Chorionic Villi Sampling↗
PubMed1988

Trisomy 7 in chorionic villi: follow-up studies of pregnancy, normal child, and placental clonal anomalies.

Cytogenetic study of chorionic villi sampled because of advanced maternal age revealed, after overnight culture, an apparently non-mosaic trisomy 7. Amniocentesis showed exclusively normal mitoses, and the pregnancy continued normally. One hundred mitoses from cord blood of the normal newborn revealed a non-mosaic 46,XX complement. No cells with a proven trisomy 7 were found in cultures from either of two biopsies of the morphologically normal placenta, but the peripheral biopsy showed in multiple cultures an abnormal clone: 47,XX, +20, -2, -21, +t(2;21)(p13;q22). To our knowledge, this is the first case of non-mosaic trisomy 7 detected on CVS which has had follow-up studies of amniotic fluid, cord blood, and term placenta.

Adult↗
PubMed1987

Cytogenetic studies of human testicular germ cell tumours.

In a search for consistent cytogenetic alterations in testicular germ cell cancers we have thus far studied some twenty surgical specimens of seminomas and nonseminomatous tumours. From the literature and our results it is now clear that such testicular tumours generally have a hyperdiploid to hypotriploid chromosomal content, and frequently possess a possibly site-specific chromosomal marker, an isochromosome 12p. A significant correlation between the presence of the i(12p) and advanced clinical stages has been revealed in our study. Several other chromosomal regions are consistently involved in cytogenetic changes: 1p and 1q, 6q, 7p, 9q, 12p, 17q, and 22q. Although there is little doubt that characteristic chromosomal lesions exist in testicular germ cell tumours, the impact which specific lesions may have on tumour progression is still unclear.

Chromosome Aberrations↗
PubMed1986

Lethal multiple pterygium syndrome: report of a new case with hydranencephaly.

A 28-week male fetus with the cardinal signs of the lethal multiple pterygium syndrome (multiple pterygia, congenital joint contractures, lung hypoplasia, facial abnormalities, and hydrops) is reported here. In addition, he had hydranencephaly, an anomaly not yet reported in this group of conditions. This potentially new form of the lethal multiple pterygium was detected prenatally by ultrasound examination. In discussing the case, we consider the probable autosomal recessive inheritance pattern and raise questions about the etiology and heterogeneity of this syndrome.

Anencephaly↗