Cryptic 7q21 and 9p23 deletions in a patient with apparently balanced de novo reciprocal translocation t(7;9)(q21;p23) associated with a dystonia-plus syndrome: paternal deletion of the epsilon-sarcoglycan (SGCE) gene.

We report on a boy with myoclonus-dystonia (M-D), language delay, and malformative anomalies. Genetic investigations allowed the identification of an apparently balanced de novo reciprocal translocation, t(7;9)(q21;p23). Breakpoint-region mapping using fluorescent in situ hybridization (FISH) analysis of bacterial artificial chromosome (BAC) clone probes identified microdeletions of 3.7 and 5.2 Mb within 7q21 and 9p23 breakpoint regions, respectively. Genotyping with microsatellite markers showed that deletions originated from paternal alleles. The deleted region on chromosome 7q21 includes a large imprinted gene cluster. SGCE and PEG10 are two maternally imprinted genes. SGCE mutations are implicated in M-D. In our case, M-D is due to deletion of the paternal allele of the SGCE gene. PEG10 is strongly expressed in the placenta and is essential for embryo development. Prenatal growth retardation identified in the patient may be due to deletion of the paternal allele of the PEG10 gene. Other genes in the deleted region on chromosome 7 are not imprinted. Nevertheless, a phenotype can be due to haploinsufficiency of these genes. KRIT1 is implicated in familial forms of cerebral cavernous malformations, and COL1A2 may be implicated in very mild forms of osteogenesis imperfecta. The deleted region on chromosome 9 overlaps with the candidate region for monosomy 9p syndrome. The proband shows dysmorphic features compatible with monosomy 9p syndrome, without mental impairment. These results emphasize that the phenotypic abnormalities of apparently balanced de novo translocations can be due to cryptic deletions and that the precise mapping of these aneusomies may improve clinical management.

Screening of vibration-induced disorders in the building industry using digital tactilometry. Results of a field study.

As occupational physicians in the building industry, we observed among these workers a high frequency of vibration exposure, during different tasks. We intended to study vibration exposure effects on vibration perception thresholds measured by digital tactilometry in this population of construction workers. A cross-sectional field study was made, 405 subjects were examined; each of them answered a questionnaire, underwent a medical examination and performed a test measuring his vibration perception thresholds, 150 subjects constituted the reference group. A close relationship between age and thresholds among the non-exposed group was observed. A threshold normalization of age of study the 204 exposed subjects was applied. Two exposure indices allowing time dependency vibration exposure analysis were defined the present daily exposure and cumulated exposure. In the examined population, thresholds rise with the present daily exposure in hours per day for 125 Hertz, while no significant influence of cumulated exposure is apparent. It was also pointed out that subjects exposed more than one and a half hour per day have higher thresholds than reference subjects, even if they do not have any clinical neurological complaints. This results seems to indicate the infraclinical feature of the test. These results suggest that screening of hand-arm vibration exposed population should be developed using this method. As occupational physicians in the construction industry, practising in Paris and surrounding areas, the authors studied the relationship between neurological disorders measured by vibrotactile perception thresholds, and hand-arm vibration exposure, among workers. They present the results of a field study they led within their institute, in collaboration with the tested workers' firms, and with the financial participation of the French Ministry of Labour.

Prenatal exclusion of X-linked hydrocephalus-stenosis of the aqueduct of Sylvius sequence using closely linked DNA markers.

X-linked hydrocephalus-stenosis of the aqueduct of Sylvius sequence (H-SAS, MIM number 307,000) is a rare genetic disorder characterized by hydrocephalus, macrocephaly, adducted thumbs, spasticity, mental retardation, and cerebral malformations. This regularly lethal condition is usually diagnosed at birth or prenatally by ultrasound, but hydrocephalus may be moderate or even undetectable on fetal ultrasound examination. Moreover, since heterozygous women are asymptomatic, carrier detection is at present impossible before the birth of an affected son. Therefore, mapping the H-SAS locus to distal Xq (Xq28) was of primary importance for genetic counselling and prenatal diagnosis. Here, we report prenatal exclusion of H-SAS with a probability of 97.6 per cent in two male fetuses with a 50 per cent a priori risk of being affected using closely linked Xq28 DNA markers.

Localization of aldolase C mRNA in brain cells.

The expression of aldolase C and aldolase A mRNA was assessed by Northern blot hybridization using RNAs purified from cultured rat and mouse brain neurons and astroglial cells. Neurons were found to contain about 4-fold more aldolase C mRNA and about twice as much aldolase A mRNA than astroglia. Analysis of the cellular localization of aldolase C mRNA by in situ hybridization to brain slices showed a predominantly neuronal labeling with an irregular distribution. A strong signal was observed in Purkinje cell somata and a weaker signal in subpopulations of neurons in cerebral cortex, striatum, hippocampus, hypothalamic nuclei and primary olfactory cortex.

The brain-specific gene for rat aldolase C possesses an unusual housekeeping-type promoter.

A DNA fragment encompassing the first exon and about 750 bp of the 5'-flanking sequence has been isolated and sequenced. The gene has multiple start sites of transcription which are dispersed over about 200 bp. The promoter lacks TATA and CAAT boxes and is very G + C-rich, with putative binding sites for the transcriptional factors Sp1 and AP2. Similar features are shared with two other brain-specific genes encoding thy-1 antigen and gamma-enolase. The existence of a conserved block of similarity upstream of the human and rat aldolase C genes suggests that this region could be involved in tissue-specific expression whose mechanism seem to be, at least in part, transcriptional.

[Proximal trisomy 19q. Interstitial deletion and ring chromosome derived from 19q]. / Trisomie 19q proximale. Délétion interstitielle et chromosome en anneau dérivés du 19q.

A proximal 19q duplication was observed in lymphocytes of a young boy with mental retardation, dysmorphism (weight excess, macrocephaly, downward slanted palpebral fissures, hypertelorism, broad nose, typical mouth), without visceral malformation. His mother had an interstitial deletion and ring chromosome derived from 19q.

Molecular cloning and expression of rat aldolase C messenger RNA during development and hepatocarcinogenesis.

A rat brain cDNA library was screened at low stringency with an aldolase B cDNA probe corresponding to the coding sequence of the mRNA, then at high stringency with a 3' non-coding aldolase A cDNA probe. One clone, which hybridized only under the first conditions, was further characterized and used to screen the library again. Two overlapping clones, complementary to aldolase C mRNA, were obtained. They cover the 113 carboxy-terminal coding residues and the 3' non-coding region up to the poly(A) tail. Their nucleotide sequence was determined. In the coding region the overall homology with aldolase A was 67% at the nucleotide level and 76% at the protein level. With aldolase B these values were 63% and 65% respectively. The 3' non-coding region was 380 bases long and did not exhibit any homology with the untranslated 3' extension of aldolase A and B mRNAs. Southern blot analysis indicates that probably a single aldolase C gene exists per haploid genome. Aldolase C mRNA was detected at low concentration in practically all the foetal tissues and its expression markedly and rapidly decreased after birth. In brain the concentration of aldolase C mRNA remained high and stable even after birth. Aldolase C mRNA is approximately 50-fold more abundant in brain than in foetal tissues, which are the richest in messenger RNA. In the course of azo-dye hepatocarcinogenesis the aldolase C gene is re-expressed early, with a maximum at the 4th week of carcinogenic diet, which probably corresponds to the maximal proliferation of the oval cells.

Protein ADP-ribosylation in rat liver cytosol.

ADP and poly ADP-ribosylation are post-translational modifications of proteins which have been reported to occur essentially in eucaryotic nuclei. This phenomenon has been shown to interfere with a great variety of biological functions (cell differentiation, DNA repair, malignant transformation...). In this paper, we demonstrate for the first time that ADP-ribosylation occurs also in cytosol (120 000 g supernatant) and that several cytosolic proteins can be ADP-ribosylated in rat liver.

Transcutaneous PO2 monitoring (tcPO2) in the newborn during apneic spells, convulsions, cardiac catheterizations, and exchange transfusions.

Continuous transcutaneous PO2 recording improves the monitoring of critically ill infants and newborns submitted to invasive procedures such as exchange transfusions or cardiac catheterization. The measurement of tcPO2 in babies with apneic spells or seizures gives a better understanding of these respiratory disorders. It is reasonable to recommend the continuous monitoring of PO2 with a transcutaneous electrode in neonatal intensive care units.

Hyperanodic forms of human glucose-6-phosphate dehydrogenase.

Pure glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate:NADP+ 1-oxidoreductase, EC 1.1.1.49) is transformed into 'hyperanodic forms' when incubated at acidic pH and in the presence of NADP+ with excess of glucose-6-phosphate or with some 'NADP+ modifying proteins' purified from the same cells. The enzyme hyperanodic forms exhibit low isoelectric point, altered kinetic properties and high lability to heat, urea, and proteolysis. Differences between hyperanodic and native forms of glucose-6-phosphate dehydrogenase are also noted by microcomplement fixation analysis, ultraviolet absorbance difference spectrum and fluorescence emission spectrum. Drastic denaturation of the enzyme by urea and acid treatment did not suppress the difference of isoelectric point between native and hyperanodic forms of glucose-6-phosphate dehydrogenase. From our data we suggest that the conversion into hyperanodic forms could be due to the covalent binding on the enzyme of a degradation product of the pyridine nucleotide coenzyme. This modification could constitute a physiological transient step toward the definitive degradation of the enzyme.

Assignment of NADH-cytochrome b5 reductase (DIA1 locus) to human chromosome 22.

NADH-cytochrome b5 reductase (DIA1, EC. 1.6.2.2) from human fibroblasts and from Chinese hamster cells, both identified by immunologic studies, were clearly distinguished after polyacrylamide gel isoelectro-focusing followed by staining for NADH diaphorase activity. In thirteen independent man-hamster hybrids, the human enzyme DIA1 presented a positive correlation with the human chromosome G22. Eight hybrids were DIA1(+) G22(+) and five hybrids were DIA1(-) G22(-). These data agree with the recent assignment of DIA1 to chromosome G22 by Fisher et al. (1977a). We assume that this newly assigned locus codes for both soluble and microsomal forms of NADH-cytochrome b5 reductase.

Characterization of a variant of beta-hexosaminidase: "hexosaminidase Paris".

A family (father and daughter) was found with a deficiency of hexosaminidase (HEX A and HEX B). Residual HEX A activity was about 30% of usual heterozygotes with very little HEX B activity. Thermostability of HEX A was decreased. No immunological cross reacting material was found for HEX A or B. The mechanism seems to be the production of abnormal, unstable beta subunits, which are still capable of combining with alpha subunits to form functional HEX A.

Electrophoretic modifications of three enzymes in extracts of human and bovine lens. Posttranslational "aging" of lens enzymes.

Electrophoretic modifications have been found in extracts from human and bovine lenses for three enzymes: glucose-6-phosphate dehydrogenase, triosephosphate isomerase and nucleoside phosphorylase. Increased anodic mobility is observed in all cases. It is more pronounced than in red cell lysates, also more evident in lenses from adult than from young animals. These results give evidence of posttranslational "aging" of enzyme molecules in lenses.