Biomedical subjects
Publications and source records attributed to C Turleau.
Molecular investigations were done in a woman with a de novo balanced t(21q21q) discovered because of the birth of a trisomic 21 baby. Polymorphisms detected with probe ets-2 after Msp I digestion showed that both chromosomes 21 involved in the rearrangement were of maternal origin. The most likely hypothesis is that of a disomic 21 oocyte fertilized by a nullisomic 21 sperm.
Drash syndrome associates a nephropathy characterized by a diffuse mesangial sclerosis of early onset, Wilms tumor, and male pseudohermaphroditism (MPH). A patient with Drash syndrome is reported with the following: karyotype 46,XY, external genitalia near normal female, mixed gonadal dysgenesis, severe androgen receptor deficiency demonstrated for the first time in this syndrome. The possibility of a common genetic denominator with the del 11p13 WAGR complex is suggested. MPH/nephroblastoma association is common. Androgen receptor deficiency has been observed in one case of each syndrome, respectively.
The two probes H3-8 and H2-42, known to be located in 13q14, were mapped by in situ hybridization to either side of the 13 breakpoint of an apparently balanced de novo t(2;13)(p24.3;q14.2) detected in a patient with retinoblastoma as the only phenotypic manifestation.
A patient with the phenotype of trisomy 21 (Down syndrome) was found to have a normal karyotype in blood lymphocytes and fibroblasts. Assessment of the chromosome 21 markers SOD1, CBS, ETS2, D21S11, and BCEI showed partial trisomy by duplication of a chromosome segment carrying the SOD1, CBS, and ETS2 loci and flanked by the BCEI and D21S11 loci, which are not duplicated. This submicroscopic duplication at the interface of 21q21 and 21q22.1 reduces to about 2000-3000 kb the critical segment the trisomy of which is responsible for the phenotype of trisomy 21.
The improvement of chromosome banding techniques has much increased the frequency of detected forms of retinoblastoma. Ten rearrangements involving 13q14 were observed in a series of 105 retinoblastoma patients including: five de novo deletions, one of them with suspected mosaicism; one de novo apparently balanced translocation; four deletions due to three familial insertions. Such a mechanism could account for pedigrees showing transmission of the tumor through unaffected carriers. Apparently unrelated rearrangements were also observed. Clinical aspects of these constitutional rearrangements are briefly discussed. Comparison with the literature data is presented.
The beta amyloid protein gene (AD-AP) has been assigned by in situ hybridization to the vicinity of the 21q21-q22.1 interface, in a normal individual as well as in a patient with Alzheimer disease.
A cytogenetical analysis was performed on 151 unfertilized oocytes, 22 fertilized eggs at the pronuclear stage, and 108 cleaved embryos obtained in the course of in vitro fertilization (IVF). Thirty-two per cent of unfertilized oocytes were abnormal, carrying nullisomies or disomies, mainly of D and G chromosomes, and a structural anomaly (Gq-) in one case. Fertilized eggs showed frequent asynchronism in the development of pronuclei and only 2 out of 8 karyotyped pronuclei were normal. Cleaved embryos were classified according to the number of pronuclei observed 17 hours after insemination. One per cent displayed a single pronucleus, and haploid chromosome complements were found in the corresponding cleaved embryos which were considered to be parthenotes. The rate of chromosome abnormalities of diploid eggs depended on their morphological aspect. Healthy cleaved embryos carried 12.5% of anomalies while this rate reached 37% in fragmented embryos (p less than 0.05). Lastly, 6% of fertilized eggs displayed three pronuclei or more. Only 41% of the corresponding embryos were triploid. Diploidy or diploidtriploid mosaicism were often encountered. This leads to a 21% rate of abnormalities in the preimplantation embryos. Parental karyotyping and HLA typing were carried out in a series of eight couples with in vitro idiopathic infertility or recurrent embryo degeneration in vitro. No abnormality was noted. According to these results, a model of natural selection of normal conceptuses is proposed.
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Hypomelanosis of Ito (incontinentia pigmenti achromians), a sacrococcygeal complex dysembryoma, seizures, severe cerebral lesions, mental retardation, chorioretinal atrophy, hemihypotrophy of the body, and skeletal anomalies are reported in a female infant of North African origin. Karyotype analysis revealed mosaicism for a microdeletion of the proximal region of 15q similar to that observed in Willi-Prader syndrome. The possibility of gene assignment of Ito's disease or that it may represent a nonspecific marker for mosaicism are discussed.
Sixty-six retinoblastoma patients were investigated using high resolution banding techniques, sister chromatid exchange (SCE) studies, and esterase-D phenotype determination and dosage. Seven patients (in six families) were found to be carriers of a rearrangement of band 13q14 due to de novo deletions, apparently balanced de novo translocations, or parental insertions. The possible role of submicroscopic parental insertions is suggested to explain transmission of nonchromosomal forms through unaffected carriers.
We used a cloned cDNA probe for the B subunit of human aldolase (ALDB) and Southern blotting techniques to analyse DNA from a series of rodent X human somatic cell hybrids for the presence of specific ALDB-related sequences. Our results provide evidence for the assignment of the gene for ALDB to chromosome 9. Moreover, by direct gene dosage determination in two patients with chromosome 9 unbalanced rearrangements and by in situ hybridization we refined the regional chromosomal assignment to 9q13----q32 and most probably to 9q21.3----9q22.2.
This report describes a male infant with partial trisomy 2q: 46,Y,der(X),t(X;2) (p22.3;q32.1)mat. The phenotype was compatible with partial trisomy 2q syndrome. Replication studies showed a random X inactivation in the mother. Soluble isocitrate dehydrogenase (IDH-1) dosage was within the expected range for a trisomic patient and favours the assignment of this locus to the region 2q32----qter.
Thirteen previously unreported patients with Beckwith-Wiedemann syndrome are reported. They include two unrelated patients having developed nephroblastoma, and three sibs. High resolution banding techniques failed to show any evidence of trisomy 11p15 in any of these 13 patients. The clinical pictures of Beckwith-Wiedemann syndrome with and without trisomy 11p15 are compared.
A 45,X/46,X,r(X) mosaicism was observed in an incontinentia pigmenti (Bloch-Sulzberger form) female patient, with mental retardation, short stature, and minor dysmorphisms. This observation is compatible with the regional assignment of the incontinentia pigmenti locus to the juxta-centromeric region of the X, the r(X) being of very small size.
The embryonic testicular regression syndrome associated with severe mental retardation is reported in three 46,XY sibs each of whom has a 46,XY chromosome complement. A fourth sib, a sister, also is severely retarded mentally; her chromosome complement is 46,XX. The 46,XY individuals, who were raised as females, presented varying degrees of genital ambiguity, indicating that their gonadal activities had been arrested at different times during embryogenesis. No trace of gonadal tissue could be found in either patient. The coincidence of the embryonic testicular regression syndrome and severe mental retardation in the same sibship is discussed.
Two patients with trisomy 11p15 and features of Beckwith-Wiedemann syndrome are reported. The first is a female infant with gigantism, macroglossia, abdominal hypotonia with umbilical hernia, moderate mental retardation, malformative uropathy, and atrial septal defect. Trisomy 11p15 was due to de novo duplication. The second patient was a stillborn (32-33 weeks pregnancy) with an abnormal tongue, posterior diaphragmatic eventration, inner organ congestion mainly of the adrenals. Trisomy 11p15 was due to a t(4;11)(q33;p14)pat. The association of trisomy 11p15 and Beckwith-Wiedemann syndrome is discussed with regard to cytogenetic data and the gene content of 11p, notably the genes coding for insulin and predisposition to Wilms tumour.
Blood clotting factors were investigated in a patient with trisomy 8 mosaicism, a patient with an r(13), and a patient with distal trisomy 13q. Results are compatible with the assignment of the structural genes of factors VII and X to 13q34 and the existence of a regulatory mechanism associated with chromosome 8 controlling the expression of factor VII alone.
A patient is reported with del11p13, low catalase level, nephroblastoma, chordee and cryptorchidism, no evident mental retardation, and with normal irides. This unique observation suggests the following order of loci in 11p13, from centromere to telomere: catalase, Wilms tumor, aniridia. The chromosomal origin of nephroblastoma may be more frequent than estimated on the basis of its association with aniridia.