De novo mosaic 46,XX,del(3)(q21q25)/46,XX karyotype in a patient with BPES.
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Blepharophimosis↗
Biomedical subjects
E Back
Publications and source records attributed to E Back.
A translocation breakpoint cluster disrupts the newly defined 3' end of the SNURF-SNRPN transcription unit on chromosome 15.
Balanced translocations affecting the paternal copy of 15q11--q13 are a rare cause of Prader-Willi syndrome (PWS) or PWS-like features. Here we report on the cytogenetic and molecular characterization of a de novo balanced reciprocal translocation t(X;15)(q28;q12) in a female patient with atypical PWS. The translocation breakpoints in this patient and two previously reported patients map 70-80 kb distal to the SNURF-SNRPN gene and define a breakpoint cluster region. The breakpoints disrupt one of several hitherto unknown 3' exons of this gene. Using RT--PCR we demonstrate that sequences distal to the breakpoint, including the recently identified C/D box small nucleolar RNA (snoRNA) gene cluster HBII-85 as well as IPW and PAR1, are not expressed in the patient. Our data suggest that lack of expression of these sequences contributes to the PWS phenotype.
Adult↗
De novo inverted duplication of chromosome 7(q21.3-->q35): cytogenetic diagnosis confirmed by FISH analysis.
We report on a newborn female patient with a de novo pure partial duplication of 7q. The clinical features are compared with those of 19 cases from the literature with pure partial duplication of different segments of 7q. Conventional cytogenetic investigation led to the diagnosis of duplication of bands q21.3 to q35. This was confirmed by chromosome painting and by fluorescence in situ hybridization with different YAC probes from the duplicated region.
Child, Preschool↗
Campomelic dysplasia translocation breakpoints are scattered over 1 Mb proximal to SOX9: evidence for an extended control region.
Campomelic dysplasia (CD), a skeletal malformation syndrome with or without XY sex reversal, is usually caused by mutations within the SOX9 gene on distal 17q. Several CD translocation and inversion cases have been described with breakpoints outside the coding region, mapping to locations >130 kb proximal to SOX9. Such cases are generally less severely affected than cases with SOX9 coding-region mutations, as is borne out by three new translocation cases that we present. We have cloned the region extending 1.2 Mb upstream of the SOX9 gene in overlapping bacterial-artificial-chromosome and P1-artificial-chromosome clones and have established a restriction map with rare-cutter enzymes. With sequence-tagged-site-content mapping in somatic-cell hybrids, as well as with FISH, we have precisely mapped the breakpoints of the three new and of three previously described CD cases. The six CD breakpoints map to an interval that is 140-950 kb proximal to the SOX9 gene. With exon trapping, we could isolate five potential exons from the YAC 946E12 that spans the region, four of which could be placed in the contig in the vicinity of the breakpoints. They show the same transcriptional orientation, but only two have an open reading frame (ORF). We failed to detect expression of these fragments in several human and mouse cDNA libraries, as well as on northern blots. Genomic sequence totaling 1,063 kb from the SOX9 5'-flanking region was determined and was analyzed by the gene-prediction program GENSCAN and by a search of dbEST and other databases. No genes or transcripts could be identified. Together, these data suggest that the chromosomal rearrangements most likely remove one or more cis-regulatory elements from an extended SOX9 control region.
Adolescent↗
De novo duplication of 12pter-->p12.1: clinical and cytogenetic diagnosis confirmed by chromosome painting.
A 12.5-year-old male patient with a de novo derivative chromosome 22 is reported. A detailed description of the clinical features and comparison with the results of conventional cytogenetic banding methods indicated that the derivative chromosome might have been caused by a translocation between the short arms of chromosomes 12 and 22: der(22)t(12;22)(p12.1;p11.2). Fluorescence in situ hybridization with a chromosome 12-specific paint confirmed this supposition. The patient thus carries a pure duplication of 12pter-->p12.1. The phenotype of the patient described is compared to cases in the literature.
Adolescent↗
A somatic cell hybrid panel for distal 17q: GDIA1 maps to 17q25.3.
A somatic cell hybrid panel was constructed consisting of seven hybrids with translocation breakpoints spanning the region 17q23-->q25. Hybrid clones carrying the longarm derivative of chromosome 17 in the absence of the normal chromosome 17 and of the derivative 17 were initially identified by PCR typing for a proximal and distal 17q marker. The translocation breakpoints of the hybrids were then mapped in more detail by PCR analysis for a number of microsatellite markers from chromosome 17q as well as for five gene loci (CACNLG, GH1, SOX9, TIMP2, TK1) previously mapped to the region 17q23-->q25. In addition, the locus for GDIA1 was mapped by FISH to 17q25.3 and fine mapped with the help of the hybrid panel. These seven new hybrids complement the existing somatic cell hybrid panel for the long arm of chromosome 17q.
Animals↗
De novo duplication of 7pter-->p21.2 and deletion of 9pter-->p23.5: clinical and cytogenetic diagnosis.
We report on a male patient with a de novo derivative chromosome 9. From clinical and conventional cytogenetic data, it was assumed that the derivative chromosome might be caused by a translocation between the short arms of chromosomes 7 and 9: der(9)t(7;9)(p21.2;p23.5). Fluorescence in situ hybridization with a chromosome 7-specific and a chromosome 9-specific paint confirmed this supposition. The phenotype of the patient described is compared to cases in the literature.
Abnormalities, Multiple↗
Isochromosome Xq in Klinefelter syndrome: report of 7 new cases.
In this collaborative study we report on 2 prenatally and 5 postnatally diagnosed cases with a 47,X,i(Xq),Y chromosomal constitution. Excepting tall stature, the 5 adult patients showed all typical manifestations of Klinefelter syndrome. Taken together with previously reported cases, these data suggest that Klinefelter syndrome with isochromosome Xq has a favorable prognosis with normal mental development, and with normal-to-short stature. The prevalence of this Klinefelter variant is calculated to be between 0.3-0.9% in males with X chromosome polysomies.
Adult↗
Two unrelated children with developmental delay, short stature and anterior chamber cleavage disorder, cerebellar hypoplasia, endocrine disturbances and tracheostenosis: a new entity?
Two unrelated children with developmental delay, anterior chamber-cleavage disorder, proportionate short stature and striking similarity in facial appearance appear to have an identical syndrome. Peters' plus syndrome has to be considered but additional abnormalities not described in this syndrome and their apparently different facies may be evidence for a hitherto undescribed condition. The further malformations both children have in common are cerebellar hypoplasia, hypothyroidism, tracheostenosis and dislocated hips.
Abnormalities, Multiple↗
De novo isochromosome 18p in two patients: cytogenetic diagnosis and confirmation by chromosome painting.
This report concerns two patients with clinical features typical for tetrasomy 18p syndrome. Chromosomal analysis revealed a male karyotype in both cases, with an additional small metacentric marker chromosome, putatively an i(18p). Fluorescent in situ hybridization with a chromosome 18-specific paint confirmed that the marker chromosome consisted of chromosome 18 material in both cases.
Abnormalities, Multiple↗
Two brothers with characteristic facial appearance, severe psychomotor retardation, hypospadias, contractures, and other symptoms: a new recessive syndrome?
We report on two severely mentally retarded male children of consanguineous parents who seem to be affected by an identical syndrome. The main physical anomalies are typical facial stigmata with a broad nasal bridge, a bulbous nose, upward slanting palpebral fissures, microretrognathia, low hair line, and large ears with an incompletely developed upper helix. In addition, both brothers had hypospadias type II, limb contractures, and delayed bone age. One child had a bilateral cleft lip with cleft palate and cryptorchidism, and developed scoliosis during adolescence. The other had bilateral inguinal hernias and strabismus. Chromosome analysis showed a normal karyotype in both. The striking similarity between the brothers, the dissimilarity to other known syndromes, and the parental consanguinity argue in favour of a new, hitherto undescribed, possibly autosomal recessive syndrome.
Abnormalities, Multiple↗
A retrospective CISS hybridization analysis of a case with de novo translocation t(18;22) resulting in an 18p- syndrome.
An unbalanced de novo translocation t(18;22) leading to a severely malformed liveborn girl with 18p- syndrome is described. Using the chromosomal in situ suppression (CISS) hybridization technique on 4-year-old G-banded chromosome preparations, it could be demonstrated that the translocation chromosome is composed of the long arm including the centromere of a chromosome 22 and the long arm of a chromosome 18. Consequently, the patient described here has lost the short arm including the centromere of chromosome 18. The possibility of restudying cytogenetically unsolved cases in clinical cytogenetics using older G-banded chromosome preparations with the fluorescence in situ hybridization techniques is pointed out.
Adult↗
Clinical, cytogenetic and molecular investigations in three patients with Wolf-Hirschhorn syndrome.
Clinical, cytogenetic and molecular studies were performed in three patients with Wolf-Hirschhorn syndrome (WHS). In all cases the altered chromosome 4 appeared to be the result of a de novo deletion. Cytogenetic investigations located the breakpoint at 4p15.3 and 4p13. With cytogenetic methods it was not possible to decide whether these deletions were terminal or interstitial. DNA methods also failed to define a distal breakpoint within the 4p16.3 region which might have indicated an interstitial deletion. According to the literature, the paternal chromosome 4 is preferentially deleted in most patients with WHS. DNA analysis with polymorphic markers out of the 4p16.3 region revealed that in two of the cases reported here the deleted segment was of paternal and in one case of maternal origin.
Abnormalities, Multiple↗
Isolation of the spinach nitrite reductase gene promoter which confers nitrate inducibility on GUS gene expression in transgenic tobacco.
Nitrite reductase is the second enzyme in the nitrate assimilatory pathway. The transcription of this gene is regulated by nitrate as well as a variety of other environmental and developmental factors. Genomic clones containing the entire nitrite reductase gene have been isolated from a spinach genomic library and sequenced. The sequence is identical in the transcribed region to a previously isolated spinach NiR cDNA clone (Back et al., 1988) except for the presence of three introns. The analysis of the genomic clones and DNA blot hybridization demonstrates that there is a single NiR gene per haploid genome in spinach. This is in contrast to what has been found for other plant species. The transcription initiation site has been determined by S1 mapping and the 5' upstream region has been used to regulate the GUS reporter gene in transgenic tobacco plants. This gene was found to be regulated by the addition of nitrate in the transgenic plants.
Amino Acid Sequence↗
Homozygous condition for a BrdU-requiring fragile site on chromosome 12.
A rare BrdU-sensitive fragile site, designated FRA12C*RQ24.2 has a relatively high frequency in the normal population. It can be demonstrated in a heterozygous and homozygous condition. There is no evidence that a phenotypic abnormality is associated with the expression of this site. A comparison with the fragile site FRA10B*RQ25.2 has revealed common features with FRA12C*RQ24.2.
Bromodeoxyuridine↗
Familial ring (20) chromosomal mosaicism.
Ring (20) chromosomal mosaicism defined by two cell lines (one normal and the other with the ring) has been demonstrated in lymphocyte and fibroblast cultures from three members of a family through two generations. Two carriers of the ring chromosome were affected and showed the typical signs of r(20) syndrome including mental retardation, microcephaly, behavioral disorders, and epilepsy. The epilepsy is characterized by complex partial seizures sometimes evolving secondarily into generalized tonic-clonic seizures and is poorly controlled by or resistant to medical treatment. The mother of the two patients, also a carrier of ring (20) chromosomal mosaicism, was clinically and phenotypically normal and did not exhibit any signs of epilepsy. Lymphocyte and fibroblast cultures from the most severely affected sib, the proband, contained the highest percentage of cells with ring (20) chromosome and revealed the greatest instability of the ring. Though it is assumed that the ring (20) chromosome arose from terminal breakage and reunion in both arms, no loss of genetic material could be documented cytogenetically. Yet the question arises of how ring chromosomal mosaicism can be passed on. One explanation might be that a chromosome 20 predisposed to terminal lesions or breaks is transmitted from the mother to her offspring. Inherited instability of this type might lead to de novo formation of the ring.
Adolescent↗
Transient Accumulation of Nitrite Reductase mRNA in Maize following the Addition of Nitrate.
Expression of the gene coding for nitrite reductase (NiR) is induced upon the addition of nitrate. We have analyzed this induction process in hydroponically grown maize (Zea mays L.) seedlings where the level of nitrate in the medium can be easily manipulated. There is a rapid induction of NiR mRNA upon addition of nitrate, increasing first in the roots and then in the leaves. The rapidity of the response depends on the nitrate concentration and the growth medium. However, the general pattern of expression is the same: the mRNA level increases, reaches a maximum, and then decreases, despite the fact that the nitrate concentration in the medium remains constant. This decline in mRNA level can be quite rapid, particularly in root tissue. If the nitrate is given as a pulse, the mRNA levels decrease even more rapidly. It is clear that the NiR mRNA is short-lived, with a half-life in the roots of less than 30 minutes. The NiR protein level, on the other hand, increases gradually somewhat after the increase in mRNA and remains at high levels at least for 24 hours after the addition of nitrate.
Journal Article↗
Genetic counseling in families with inherited balanced translocations: experience with 36 families.
We report on genetic counseling and investigations in 36 families with inherited balanced translocations ascertained in different ways, with special regard to the completeness and reasons for incompleteness of family investigation. Quantitative evaluation of the results of cytogenetic investigations shows that non-directive genetic counseling was very effective in many families. Yet, in most of the families (34) genetic counseling and investigation remained incomplete in the sense that not all living potential translocation carriers could be counseled or investigated or that the origin of a fresh mutation could not be established by a normal karyotype in the parents of a carrier. Only in seven families could nearly all living potential carriers be counseled and investigated. The most frequent reason for incompleteness was the impossibility of transmitting or refusal to transmit information about the genetic risks to relatives (21 families), whereas direct rejection of investigation by a counseled individual was a rather rare event (18 adults). Families ascertained because of an unbalanced child seem to be more willing to transmit genetic information to relatives than families ascertained in other ways. Non-directive genetic counseling gave us an insight into the emotional problems arising during counseling of translocation families.
Female↗