First-trimester prenatal diagnosis of Canavan disease.
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Amidohydrolases↗
Biomedical subjects
M Mathieu
Publications and source records attributed to M Mathieu.
Second trimester prenatal diagnosis of Sanfilippo syndrome type C.
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Acetyltransferases↗
2-Ketoglutarate dehydrogenase deficiency, a rare cause of primary hyperlactataemia: report of a new case.
Two new familial cases of 2-ketoglutarate dehydrogenase (2-KGD) deficiency are reported: a girl who died at 10 years and a boy, still alive at 4 years, born to consanguineous parents. The cases developed progressively severe encephalopathy with axial hypotonia, psychotic behaviour, pyramidal symptoms and failure to thrive. Both children exhibited permanent lactic acidosis with acute episodes during emotional stress and various infections, associated with elevated lactate/pyruvate (L/P) ratio and slightly decreased ketone body ratio in plasma. In fibroblasts, the L/P ratio was greatly increased in the boy. No respiratory chain complex deficiency could be demonstrated in cultured fibroblasts or in mitochondria isolated from a muscle biopsy performed on the boy. In muscle isolated mitochondria, a progressive decrease of the rate of glutamate oxidation was observed after ADP addition; the rate of 2-ketoglutarate oxidation was low in the absence of ADP and did not increase after ADP addition. 2-KGD deficiency was demonstrated in fibroblasts from both children and in the boy's muscle and myoblasts. The 2-KGD complex is composed of three separate enzymes: E1, E2 and E3. We could demonstrate in our patient that the E1 and E3 subunits were normal, suggesting that the E2 component could be responsible for the defect.
Acidosis, Lactic↗
Molecular analysis of a ring chromosome X in a family with fragile X syndrome.
The phenotypically normal sister of a patient affected by fragile X syndrome was referred for genetic counselling and was found to carry a mosaic karyotype 46,X,r(X)/45,X. Because the probability of the simultaneous chance occurrence of fragile X syndrome and a ring chromosome X in the same family is very low, we postulated that the breakpoint of the ring chromosome X originated in the cytogenetic break in Xq27.3 responsible for fragile X syndrome. In order to determine the relative positions of the breakpoint on the ring chromosome X and the (CGG)n unstable sequence responsible for the fragile X mutation, we used molecular markers to analyse the telomeric regions of chromosome X in this family. The results showed that the ring chromosome X was the maternal fragile X chromosome and that the telomeric deletion on the long arm encompassed the (CGG)n sequence. This suggests that the cytogenetic break in Xq27.3 is distinct from the unstable (CGG)n sequence, or that the break followed by the end-to-end fusion creating the ring chromosome was not completely conservative. Analysis of DNA markers on the short arm of chromosome X evidenced a deletion of a large part of the pseudoautosomal region, allowing us to position the genes involved in stature and in some syndromes associated with telomeric deletions of Xp on the proximal side of the pseudoautosomal region.
Adult↗
Carnitine palmitoyl transferase I deficiency presenting as a Reye-like syndrome without hypoglycaemia.
An apparently healthy girl aged 2 years 9 months developed a coma with hepatomegaly within 24 h after an influenza-like infection. Plasma glucose and urinary organic acid profile were normal but plasma and urinary carnitine concentrations were increased. Despite symptomatic therapy, she died 11 days later. Oxidation of [1-14C] palmitic acid in the patient's fibroblasts was severely decreased (13% of controls). Further investigations revealed a deficiency of carnitine palmitoyl transferase I (CPT I) in the patient's fibroblasts (15% of controls) whereas CPT II activity was normal. Only four patients with CPT I deficiency have been reported so far. The subtle clinical and biochemical presentation of this disorder, which may account for the small number of cases diagnosed, is discussed.
Carnitine↗
Similarity of drug labels predisposes to drug errors.
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Aged↗
A 45,X male with an X;Y translocation: implications for the mapping of the genes responsible for Turner syndrome and X-linked chondrodysplasia punctata.
In a male patient with a 45,X karyotype, the terminal part of the Y chromosome short arm was translocated as a single block on to the X chromosome. This rearranged X chromosome was, in every regard, the same as that present in XX males resulting from an abnormal X-Y interchange. Correlations between the phenotype of this patient and the extent of the deletions on the X and Y chromosomes allowed us to map the genes responsible for most features of the Turner syndrome between DXS432 and Xqter on the X chromosome, and the homologous Y genes either on Yp in interval 4 or on Yq. The molecular analysis of this X-Y translocation allowed us also to reduce the interval for the X-linked recessive chondrodysplasia punctata gene to a 1.5 Mb interval between DXS432 and DXS31.
Adolescent↗
Identification of three rare frameshift mutations in exon 13 of the cystic fibrosis gene: 1918delGC, 2118del4 and 2372del8.
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Base Sequence↗
Specific binding sites in the alcR and alcA promoters of the ethanol regulon for the CREA repressor mediating carbon catabolite repression in Aspergillus nidulans.
The CREA repressor responsible for carbon catabolite repression in Aspergillus nidulans represses the transcription of the ethanol regulon. The N-terminal part of the CREA protein encompassing the two zinc fingers (C2H2 class family) and an alanine-rich region was expressed in Escherichia coli as a fusion protein with glutathione-S-transferase. Our results show that CREA is a DNA-binding protein able to bind to the promoters of both the specific trans-acting gene, alcR, and of the structural gene, alcA, encoding the alcohol dehydrogenase I. DNase I protection footprinting experiments revealed several specific binding sites in the alcR and in the alcA promoters having the consensus sequence 5'-G/CPyGGGG-3'. The disruption of one of these CREA-binding sites in the alcR promoter overlapping the induction target for the trans-activator ALCR results in a partially derepressed alc phenotype and derepressed alcR transcription, showing that this binding site is functional in vivo. Our data suggest that CREA represses the ethanol regulon by a double lock mechanism repressing both the trans-acting gene, alcR, and the structural gene, alcA.
Alcohol Dehydrogenase↗
Comparison of thoracoabdominal calibration methods in normal human subjects.
In 19 normal subjects in the supine posture, we compared accuracy and precision of calibration methods that utilized different ranges of tidal volumes and thoracoabdominal partitioning: spontaneous quiet breathing (QB), isovolume maneuvers, and voluntary efforts to breathe with variable tidal volume and thoracoabdominal partitioning. Thoracic and abdominal movements were measured with the respiratory area fluxometer. Calibration methods utilizing one or more types of respiratory efforts were applied to three measurement situations: QB, variable breathing (volume and thoracoabdominal partitioning), and simulated obstructive apnea (isovolume efforts). Qualitative diagnostic calibration (QDC) included QB data only. The isovolume method (ISOCAL) included isovolumetric efforts at end expiration (functional residual capacity) and QB. Multilinear regression analyses were performed on data sets that included 1) voluntary efforts to breathe with variable volume and thoracoabdominal partitioning (CAL 1), 2) QB in addition to variable volume and partitioning (CAL 2), and 3) isovolume maneuvers in addition to QB and variable volume and partitioning efforts (CAL 3). When calibration data included a wide range of tidal volume, variable thoracoabdominal partitioning, and isovolume efforts (CAL 3), a stable calibration with small bias and scatter during all respiratory patterns was obtained. Excluding isovolume maneuvers (CAL 2) and QB (CAL 1) did not diminish accuracy. Limiting data to isovolume efforts at functional residual capacity plus QB (ISO-CAL) caused a significant increase in scatter during variable breathing patterns. Limiting calibration data to that portion of QB with small variation in the uncalibrated sum of thoracic and abdominal movements (QDC) caused significant increases in scatter in both isovolume efforts and variable breathing.
Abdomen↗
Bronchoconstriction-induced hyperinflation assessed by thoracic area measurement in guinea pigs.
The changes in end-expiratory lung volume (EELV) accompanying histamine-induced bronchoconstriction were compared for two routes of drug administration in anesthetized, paralyzed, and mechanically ventilated guinea pigs. Changes in EELV were estimated from measurements of thoracic cross-sectional area, assessed from the voltage induced by an external uniform magnetic field in a pickup coil encircling the rib cage. Increasing doses of histamine were administered as bolus injections in Group 1 (n = 7) and as nebulizations in Group 2 (n = 7). After each bronchial challenge, the maximum change in EELV and the associated intrinsic positive end-expiratory pressure (PEEPi) were measured at the same time. In both groups, bronchoconstriction was accompanied by an increase in EELV, which was related to the degree of bronchoconstriction and reached about 70 to 100% of the basal functional residual capacity. The increases in EELV were linearly related to the PEEPi values (p < 0.001) and did not depend on the route of histamine administration. These results indicate that dynamic hyperinflation is not the only mechanism involved in lung volume response to bronchoconstriction and suggest that gas trapping may have occurred in alveolar spaces.
Administration, Inhalation↗
Atrazine in plasma and tissue following atrazine-aminotriazole-ethylene glycol-formaldehyde poisoning.
A high performance liquid chromatography method has been used to study the plasma kinetics of atrazine in a human fatality after ingestion of a herbicide mix containing atrazine, aminotriazole, ethylene glycol and formaldehyde. A hemodialysis was performed in an effort to eliminate these toxic substances. The mean atrazine clearance over 4 h was 250 mL/min and the dialysance of atrazine was calculated as 76%. On autopsy, the kidney showed the highest concentration of atrazine (97.62 micrograms/g-1 wet tissue) with lesser concentrations in the lung, small intestine and liver, and the lowest concentration in the heart.
Adult↗
A familial syndrome with micrognathia, cleft palate, short neck and stature, vertebral anomalies and mental retardation.
We report on a male adult and his son both affected with hitherto undescribed multiple congenital anomalies and mental retardation. Both have peculiar facies, cleft palate, short sature, congenital brevicollis and vertebral abnormalities. Chromosomal analysis is normal and an autosomal dominant mode of inheritance is most likely. Genetic aspects and clinical manifestations are compared with those of previous reports of Robin sequence or cleft palate, short stature and vertebral dysostosis.
Abnormalities, Multiple↗
[Fundus oculi test in the detection of Gardner syndrome].
Gardner's syndrome is an adenomatous polyposis coli characterized by extracolonic manifestations such as congenital hypertrophy of retinal pigment epithelium. This inherited autosomal dominant disorder has a marked propensity to malignant transformation, so it is important to detect affected patients early. Ophthalmologic manifestations are simple, non invasive reliable and very sensitive. The gene responsible for this disorder was localized to the long arm of the fifth chromosome. The results of investigation in 3 families are reported herein and compared with the data of the literature.
Adolescent↗
A reference preparation of creatine kinase BB isoenzyme.
Creatine kinase (CK; EC 2.7.3.2) catalytic activity in serum is widely measured in clinical chemistry practice and provides information for diagnosis and follow-up in many pathological conditions affecting heart, muscle, and brain. Depending on the organ involved, the predominant CK isoenzyme in serum varies. However, routine methods measure total CK catalytic activity, and standardized methods for doing so have been recommended by the International Federation of Clinical Chemistry and by several national scientific societies. Many commercial kits for those methods are now available. With use of a reference material for CK, commercial reagents can be compared with standardized methods, improving confidence in the results. Here we present a reference preparation of CK consisting of the BB isoenzyme purified from human placentae. We describe the procedure of purification and the properties of the lyophilized preparation of CK-BB, which has been certified by the Community Bureau of Reference of the Commission of the European Communities under the designation CRM 299. The preparation can be used to calibrate assays of the catalytic activity of CK-MM and CK-MB, as well as CK-BB.
Chromatography, Ion Exchange↗
[Value of skin fibroblasts in culture for the diagnosis of mitochondrial cell dysfunction. Apropos of 5 cases with cytochrome c oxidase deficiency].
Mitochondrial respiratory chain dysfunction has been studied by two complementary methods using cultured skin fibroblasts from five patients with muscular cytochrome c oxidase (complex IV) deficiency: first, a screening test measuring lactate to pyruvate ratio (L/P) after supplementation of cultured cells; secondly, measurement of complex IV activity in whole cells. Respiratory chain defect (increased L/P ratio with decreased complex IV activity) was expressed in fibroblasts of four of the five patients. Our results show that skin fibroblasts can be helpful for biochemical diagnosis of mitochondrial respiratory chain defects.
Cells, Cultured↗
Pitfalls of screening for mucopolysaccharidoses by the dimethylmethylene blue test.
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Glycosaminoglycans↗
The Juberg-Marsidi syndrome maps to the proximal long arm of the X chromosome (Xq12-q21).
Juberg-Marsidi syndrome (McKusick 309590) is a rare X-linked recessive condition characterized by severe mental retardation, growth failure, sensorineural deafness, and microgenitalism. Here we report on the genetic mapping of the Juberg-Marsidi gene to the proximal long arm of the X chromosome (Xq12-q21) by linkage to probe pRX214H1 at the DXS441 locus (Z = 3.24 at theta = .00). Multipoint linkage analysis placed the Juberg-Marsidi gene within the interval defined by the DXS159 and the DXYS1X loci in the Xq12-q21 region. These data provide evidence for the genetic distinction between Juberg-Marsidi syndrome and several other X-linked mental retardation syndromes that have hypogonadism and hypogenitalism and that previously. Finally, the mapping of the Juberg-Marsidi gene is of potential interest for reliable genetic counseling of at-risk women.
Abnormalities, Multiple↗