Effects of X chromosome on size and shape of body: an anthropometric investigation in 47,XXY males

The effects of an extra X chromosome on size and shape of body and head were studied in 47,XXY males; 25 anthropometric measurements were recorded from 29 adult 47,XXY males and compared with those of male relatives and control males. In stature, arm length, leg length, triceps skinfold, and subscapular skinfold 47,XXY males were larger and in biacromial diameter, bideltoid breadth, wrist breadth, and in most head dimensions smaller than normal males. Arm length was increased less than leg length. Increase in stature seemed to be caused solely by increased leg length, and the somewhat feminine proportions in trunk were caused by decrease in biacromial diameter. Correlations of the body and head dimensions between 47,XXY males and their male relatives were found to be normal. The present findings support the earlier proposals that X chromosome carries genes which influence linear growth. It is suggested that the reduction in biacromial diameter is caused by lowered plasma testosterone level which may also have affected sitting height. The control of body and head dimensions seems to be maintained relatively normal.     

Syndrome de Klinefelter et diagnostic prénatal

Because of the widespread use of amniocentesis and chorionic villus sampling, antenatal diagnosis of sex chromosome anomalies, particularly 47,XXY, has become increasingly common. The clinical and laboratory features of Klinefelter syndromes are well documented. On the contrary, the intelligence and achievement outcome of patients with Klinefelter syndrome are less well documented. Early reports suggested an increased frequency of psychological disturbances, subnormal intelligence, and sociopathy; however, because this information was obtained from inmates/patients of various institutions and clinics, it is considered to be biased. Most males born with the 47,XXY pattern will go through life without being karyotyped, while the commonest indication for karyotyping of a Klinefelter male is hypogonadism and/or infertility. Parents are very anxious when they are told that their fetus is 47,XXY. The couple should be allowed to continue the pregnancy in view of the absence of developmental delay and/or behavioural problems and congenital malformations. The abortion rate is higher when the fetal abnormality is announced by an obstetrician rather than a geneticist. The current tendency is to no longer propose termination of pregnancy, as most 47,XXY males only present with infertility.     

47,XXY males: sex chromosomes and tooth size.

Permanent tooth crowns of 47,XXY males were found to be generally larger than those of control males and females and their first-degree male and female relatives. These results suggest that tooth-size increase in 47,XXY males is due to a direct genetic effect and support the concept of the presence of a specific growth gene (or genes) in the human X and Y chromosomes. The effect of this gene (or genes) seems to be the promotion of tooth growth, and the Y chromosome is more effective than the X chromosome in this respect.     

Cardiac functioning and blood pressure of 47,XYY and 47,XXY men in a double-blind, double-matched population survey.

This paper reports the electrocardiogram measures and blood pressure of 12 men with 47,XYY, 14 men with 47,XXY, and 52 matched controls with 46,XY. The abnormal karyotypes were identified in a systematic population search for XYY and XXY men. The subjects and their matched controls were examined in a double-blind fashion. Electrocardiogram measures of 47,XYY and 47,XXY men were found to differ from those of 46,XY controls. The XYYs had longer P-R intervals, shorter QRS complexes, and nonsignificantly longer R-R intervals than their matched controls. The XXYs showed longer R-R intervals and trends for for prolonged P-R intervals and shorter QRS complexes when compared with their controls. Trends toward increased within-group variability in the XYY and XXY groups were observed in five of six variance tests, suggesting that the sex chromosome aneuploids have a cardiac condition anomaly. Blood pressure measures of 47,XYY and 47,XXY men were found not to differ from those of 46,XY men. None of the measures revealed a significant difference between the XYYs and the XXYs.     

Elevated serum leptin levels in patients with acute myocardial infarction; correlation with coronary angiographic and echocardiographic findings

ABSTRACT: BACKGROUND: To assess the relationship between serial serum leptin levels in patients with acute myocardial infarction (AMI) who received thrombolysis and the degree of coronary atherosclerosis, coronary reperfusion, echocardiographic findings, and clinical outcome. 51 consecutive patients presenting with AMI were studied. Clinical characteristics including age, sex, body mass index (BMI) and cardiovascular risk factors were recorded. Serial serum leptin levels at the time of admission and subsequently at 0, 6, 12, 24, 36, 60 hours afterwards were obtained. Coronary angiography was performed in 34 patients; the relation between serum leptin levels and evidence of coronary reperfusion as well as the extent of coronary atherosclerosis according to the coronary artery surgery study classification (CASS) were evaluated. Echocardiographic evaluation was performed in all patients. 36 matched patients were enrolled as control group who had serum leptin level 9.4 +/- 6.5 ng/ml. RESULTS: The patients mean age was 50.5 +/- 10.6 years. There were 47 males and 3 females. 37.1% were diabetics, 23.5% were hypertensive, 21.6% were dyslipidemic and 22.7% were obese (BMI [greater than or equal to] 30). Leptin concentrations (ng/ml) increased and peaked at the 4th sample (36 hrs) after admission (mean +/- SD) sample (1) =9.55 +/- 7.4, sample (2) =12.9 +/- 8.4, sample (3) =13.8 +/- 10.4, sample (4) =18.9 +/- 18.1, sample (5) =11.4 +/- 6.5, sample (6) =10.8 +/- 8.9 ng/ml. There was a significant correlation between serum leptin and BMI (r = 0.342; p =0.03). Leptin levels correlated significantly to creatine kinase level on the second day (r = 0.43, p [less than or equal to] 0.01). Significant correlation of mean serum leptin with the ejection fraction (P < 0.05) was found. No difference in timing of peak serum leptin between patients who achieved coronary reperfusion vs. those who did not (p= 0.8). There was a trend for an increase in the mean serum leptin levels with increasing number of diseased vessels. There was no correlation between serum leptin levels and outcome neither during the hospitalization nor at 9 months follow up. CONCLUSION: Serum leptin levels increase after myocardial infarction. Serum leptin level may be a predictor of the left ventricular ejection fraction and the degree of atherosclerosis but not of coronary reperfusion.     

Balanced and unbalanced pericentric inversion of a chromosome 14

Summary Three males with a 46,XX karyotype are described. In two of them, evidence of a Y-containing line was found. In the first case, 1 of 500 lymphocyte metaphases was 47,XXY. In the second, 1 of 400 oral mucosa cells contained a Y body. The proportion of low-grade XX/XXY mosaics found among XX males now stands at about 17%.     

Penicillin-binding protein 2 genes of non-β-lactamase-producing, penicillin-resistant strains of Neisseria gonorrhoeae

Oligonucleotides that correspond to regions of the penicillin-binding protein 2 gene (penA) that differ between penicillin-sensitive and penicillin-resistant strains have been used as probes to classify the penA genes in a collection of penicillin-resistant gonococci isolated in Britain. 44/47 of those gonococcal strains that had minimal inhibitory concentrations of greater than or equal to 0.25 microgram benzylpenicillin per ml contained extensively altered penA genes which appeared to be very similar (or identical) to one or other of the two classes of altered penA genes that have been described previously. Since these two classes of altered penA genes are related, it appears that the great majority of the altered penA genes on non-beta-lactamase-producing penicillin-resistant gonococci have a clonal origin. The other three penicillin-resistant strains had altered penA genes that were different to those described previously. A crucial step in the development of the altered forms of PBP2 with decreased affinity for penicillin appears to have been the insertion of an extra codon within the transpeptidase domain of the penA gene. This insertion was found in the penA gene of all gonococci with minimal inhibitory concentrations of greater than 0.016 microgram benzylpenicillin per ml but was not found in any strains with minimal inhibitory concentrations of less than or equal to 0.016 microgram per ml.     

Cytogenetic evaluation of 163 azoospermics

A constitutional chromosomal aberration was diagnosed in 38/163 (23.3%) azoospermic patients. Whereas the 47,XXY complement was the commonest (31/38 cases), the following abnormal karyotypes were also found: 46,XX; 46,X,del(Y) (q11); 46,X,r(Y); 46,XY,inv(1) (p3500q21.3)mat; and 46,Y,t(X;3) (q26;q13.2)mat (both the deleted and the annular Y were observed twice). Pooled data from the literature showed that the frequency of chromosomal abnormalities is higher in azoospermic (150.4/1000) than in infertile (55.3/1000) males, which in turn is higher than in newborns (less than 6/1000). The observed different frequency between azoospermic and infertile individuals is given by several types of chromosomal abnormalities, mainly by the complement 47,XXY. The analysis also showed that the male infertility secondary to rob translocations and supernumerary marker chromosomes is usually not related to azoospermia. The contrary occurs in certain rcp and gonosome;autosome translocations and in autosome inversions.     

The nature of social cognitive deficits in children and adults with Klinefelter syndrome (47,XXY)

About 1 in 650 boys are born with an extra X chromosome (47,XXY or Klinefelter syndrome). 47,XXY is associated with vulnerabilities in socio‐emotional development. This study was designed to assess types of cognitive deficits in individuals with 47,XXY that may contribute to social‐emotional dysfunction, and to evaluate the nature of such deficits at various levels: ranging from basic visuospatial processing deficits, impairments in face recognition (FR), to emotion expression impairments. A total of 70 boys and men with 47,XXY, aged 8 to 60 years old, participated in the study. The subtests feature identification, FR and identification of facial emotions of the Amsterdam Neuropsychological Tasks were used. Level of intellectual functioning was assessed with the child and adult versions of the Wechsler Intelligence Scales. Reaction time data showed that in the 47,XXY group, 17% had difficulties in visuospatial processing (no social load), 26% had difficulties with FR (medium social load) and an even higher number of 33% had difficulties with facial expressions of emotions (high‐social load). Information processing impairments increased as a function of “social load” of the stimuli, independent of intellectual functioning. Taken together, our data suggest that on average individuals with XXY may have more difficulties in information processing when “social load” increases, suggesting a specific difficulty in the higher‐order labeling and interpretation of social cues, which cannot be explained by more basic visuospatial perceptual skills. Considering the increased risk for social cognitive impairments, routine assessment of social cognitive functioning as part of neuropsychological screening is warranted.     

Follow-up 20 years later of 34 Klinefelter males with karyotype 47,XXY and 16 hypogonadal males with karyotype 46,XY

Summary A 20-year follow-up study of 50 hypogonadal males has been made. Of these 34 had Klinefelter's syndrome with the karyotype 47,XXY and 16 had the karyotype 46,XY. These males have been examined at mean ages of 27 and 37 and in the present study at a mean age of 47. At the first examination the following conditions were found in the Klinefelter males to a significantly higher degree than in the hypogonadal males with 46,XY: immaturity, below average school performance, few or no friends, previous mental illness, little energy and initiative, few or no spare time interests, occupation as an unskilled labourer. Psychological testing showed a full scale IQ of 103 in the Klinefelter males and 115 in the hypogonadal males. The follow-up studies have shown that in spite of these findings the Klinefelter males have managed far better than could have been expected at the time of the first investigation. The improvement in a number of conditions such as mental health, working capacity, social adjustment, relations with other people, and activity level was considerable between the ages of 27 and 37. The present examination shows a further improvement at the age of 47 with the only significant difference between the Klinefelter males and the hypogonadal males with 46,XY being a higher frequency of single Klinefelter males. The present examination also showed that there was no significant difference between the two groups in occupation, working capacity, social adjustment, mental and physical disorders or criminality. The results of the examination at the mean age of 27 would probably have been considerably more favourable for the Klinefelter males if diagnosis had been made in childhood, and information, counselling, support and hormone treatment had been given from an early age. The fact that the great majority of the Klinefelter males have managed quite well in spite of this and that no remarkable differences were found between them and a control group is of great importance for genetic counsellers, especially for prenatal counsellers. Up until now, in 75% of cases in which sex chromosome abnormalities, including Klinefelter's syndrome, have been diagnosed prenatally in Denmark abortion has been induced. We believe this is mainly due to insufficient information about the many positive aspects of the development of individuals with sex chromosome abnormalities.     

The carbohydrate composition of human apo low density lipoprotein from normal and type II hyperlipoproteinemic subjects.

The carbohydrate composition of the apoprotein from low density lipoprotein (LDL) of normal (average LDL cholesterol, 122 mg/100 ml) and type II hyperlipoproteinemic (average LDL cholesterol, 236 mg/100 ml) males was studied using gas-liquid chromatographic analysis of the methul glycoside derivatives. All samples containing detectable sinking pre-beta-lipoprotein were excluded from the study. The apo LDL from both groups of subjects contained mannose, galactose, N-acetyl-glucosamine and N-acetylneuraminic acid. Glucose and fucose were not found while trace quantities of galactosamine were detected. Although the quantities of galactose and N-acetylglycosamine were the same in the two groups, lower quantities of mannose (p less than or equal to 0.01) and N-acetylneuraminic acid (p less than or equal to 0.05) were found in the type II patients as opposed to normal subjects.     

An aetiological study of 290 XXY males,with special reference to the role of paternal age

Summary Data on 290 non-mosaic 47,XXY males have been analysed for possible associations with parental ages at birth, season of birth, sex ratio among sibs, and twinning. Comparison with matched population controls revealed a highly significant association with parental age, which was fully explained by dependence on maternal age and maternal age alone. The maternal age effect was determined with greater precision than in an earlier study of the same material, in which siblings were used as controls, and was estimated to result in an increased risk of between 5% and 10% per annum (p.a.). The estimated independent effect of paternal age, after fitting maternal age, was marginally (but not significantly) negative, and excluded an increased risk in excess of 3% p.a. Paternal age therefore appears to have little if any independent significance in the aetiology of 47,XXY. After correcting for seasonal variations in the population birth rate and smoothing, there was a peak of XXY births in March and a trough in November. Though not statistically significant, the pattern resembled that reported in previous studies, and was similar for both younger and older mothers. The twinning rate for both the XXYs and their sibs, and the sex ratio among the latter, were close to the corresponding population values.     

Meiotic disjunction and embryonic lethality in trisomies derived from an X-linked translocation in the onion fly,Hylemya antiqua (Meigen)

Translocation- and tertiary trisomies (for the X-chromosomes) were obtained after testcrossing translocation heterozygous females of an X-linked “simple” translocation stock. Meiotic disjunction as judged from segregations at M II (males) and in young eggs of testcrosses (males and females) in translocation trisomics was studied. No progeny of tertiary trisomic males and females was found, but male M II could be studied. Six different orientation types appeared in translocation trisomie (2n + 1) males and these were present in equal frequencies. No adjacent II configurations were found. The small X- and Y-chromosomes and the large translocated X-chromosome of the translocation complex disjoin at random (n and n + 1 gametes) in both translocation- and tertiary trisomic males. In translocation trisomic females four different orientation types appeared. From the high frequency of two of these (together, 94.5%) it is concluded that the two normal X-chromosomes show preferential pairing and disjunction, while the translocated X-chromosome moves to either one of the two poles at random. Primary trisomic (for the X-chromosome) males (XXY) and females (XXX) were obtained from testerossed translocation trisomics. Cytological analysis of adult male progeny of testerossed XXY males showed that no random orientation for the X-, X- and Y-chromosomes occurred because half of the sons was disomic (XY) and half of them trisomic (XXY). A possible mechanism is discussed. Analysis of young eggs of testerossed XXX females indicated a segregation of 2X∶1X=1∶1. The level of “semi”-sterility as scored from testcrosses of translocation trisomies appeared to be as in translocation heterozygotes. Here again a close relation exists between “semi”-sterility and deficiencies in eggs for a large chromosomal segment. The possible use of this translocation for genetic control of insect pests is discussed.     

Meiotic studies of a 38,XY/39,XXY mosaic boar

Klinefelter's syndrome (KS) is the most common sex chromosome abnormality identified in human males. This syndrome is generally associated with infertility. Men with KS may have a 47,XXY or a 46,XY/47,XXY karyotype. Studies carried out in humans and mice suggest that only XY cells are able to enter and complete meiosis. These cells could originate from the XY cells present in mosaic patients or from XXY cells that have lost one X chromosome. In pig, only 3 cases of pure 39,XXY have been reported until now, and no meiotic analysis was carried out. For the first time in pig species we report the analysis of a 38,XY/39,XXY boar and describe the origin of the supplementary X chromosome and the chromosomal constitutions of the germ and Sertoli cells.     

Rates of trisomies 21, 18, 13 and other chromosome abnormalities in about 20 000 prenatal studies compared with estimated rates in live births

Summary Data were analyzed on the results of 19675 prenatal cytogenetic diagnoses reported to two chromosome registries on women aged 35 or over for whom there was no known cytogenetic risk for a chromosome abnormality except parental age. The expected rates at amniocentesis of 47,+21; 47,+18; 47,+13; XXX; XXY; XYY; and other clinically significant cytogenetic defects by maternal age were obtained from a regression analysis on the observed rates, using a first degree exponential model. After an adjustment for maternal age, these rates were compared with previously estimated rates by maternal age in live births. The rates of 47,+21 at amniocentesis and live birth are approximately parallel, with the latter about 80% of the amniocentesis rates. The rates of 47,+18 at amniocentesis and live birth are approximately parallel, with the live birth rates about 30% of the amniocentesis rates, consistent with high fetal mortality of 47,+18 after amniocentesis. The rates of 47,+13 at amniocentesis indicate an increase in maternal age that is not as marked as thar previously estimated in live births. The rates at amniocentesis for XXX and XXY increase with maternal age, with the rates of XXY almost identical to those estimated previously in live births, suggesting no late fetal mortality of XXY. The rates of XYY show a slight decrease with maternal age also consistent with little late fetal mortality of XYY. No consistent trend with age is seen for the pooled group of other clinically significant defects.     

Physiology of aging related to outcome in the adult respiratory distress syndrome

Thirty-nine patients with adult respiratory distress syndrome (ARDS) were enrolled in a study to identify potential age-related changes in organ system function that may help explain the apparent association between age and poor outcome in these patients. Criteria for enrollment included an arterial PO2-to-inspired O2 concentration ratio less than or equal to 200 in a clinical setting consistent with ARDS. Patients were excluded if they were less than 18 yr old, had clinical manifestations of congestive heart failure, were seropositive for the human immunodeficiency virus, or had stage II metastatic lung cancer. Patients were divided into two groups: those less than 60 yr old (mean 42 +/- 3 yr, n = 17) and those greater than or equal to 60 yr old (73 +/- 2 yr, n = 16). A group of six patients was analyzed as a separate subset based on a body temperature less than or equal to 97.5 degrees F at enrollment (hypothermic patients, 73 +/- 4 yr old). Sepsis was present in 67% of the nonhypothermic patients and in all the hypothermic patients. Mortality rates were 12% in the patients less than 60 yr and 69% in the nonhypothermic patients greater than or equal to 60 yr. All the hypothermic patients died. Sequential data obtained over 6 days were compared within and between groups. The following results were obtained. 1) The ratio of arterial PO2 to inspired O2 fraction was greater and the positive end-expiratory pressure used was significantly less in the patients greater than or equal to 60 yr old compared with the younger group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Q-banding of chromosomes in human spontaneous abortions

Chromosome studies of 242 spontaneous abortions were carried out by Q-banding technique. The abortuses were selected for study because they were phenotypically abnormal, had not progressed beyond 12 weeks development or were from women with repeated abortions. Chromosome anomalies were found in 126 (52%) of the abortuses. Of these, 71 (56%) were trisomies. Trisomies were found for all the autosomes except Nos. 1, 3, 5, 11, 17 and 18. Triploidy was the second commonest anomaly in this series, making up 26 (21%) of the total anomalies. About 70% of these had an XXY sex chromosome complement. Only 16 (13%) of the abortuses had X monosomy, a lower frequency than would be expected in an unselected study. Tetraploidy was found in 8 abortuses and the 5 remaining specimens had various anomalies. These included 3 translocations, a trisomy 21,X monosomy and a ring chromosome 13. Except for the greater frequency of XXY than XXX sex chromosomes in the triploids, there was no evidence of a distortion of the sex ratio, either among the trisomic or among the chromosomally normal abortuses.     

Survival of Male Patients with Incontinentia Pigmenti Carrying a Lethal Mutation Can Be Explained by Somatic Mosaicism or Klinefelter Syndrome

Incontinentia pigmenti (IP), or "Bloch-Sulzberger syndrome," is an X-linked dominant disorder characterized by abnormalities of skin, teeth, hair, and eyes; skewed X-inactivation; and recurrent miscarriages of male fetuses. IP results from mutations in the gene for NF-kappaB essential modulator (NEMO), with deletion of exons 4-10 of NEMO accounting for >80% of new mutations. Male fetuses inheriting this mutation and other "null" mutations of NEMO usually die in utero. Less deleterious mutations can result in survival of males subjects, but with ectodermal dysplasia and immunodeficiency. Male patients with skin, dental, and ocular abnormalities typical of those seen in female patients with IP (without immunodeficiency) are rare. We investigated four male patients with clinical hallmarks of IP. All four were found to carry the deletion normally associated with male lethality in utero. Survival in one patient is explained by a 47,XXY karyotype and skewed X inactivation. Three other patients possess a normal 46,XY karyotype. We demonstrate that these patients have both wild-type and deleted copies of the NEMO gene and are therefore mosaic for the common mutation. Therefore, the repeat-mediated rearrangement leading to the common deletion does not require meiotic division. Hypomorphic alleles, a 47,XXY karyotype, and somatic mosaicism therefore represent three mechanisms for survival of males carrying a NEMO mutation.     

The dermatoglyphics of a Toronto sample of children with XXY,XXYY, and XXX aneuploidies

Dermatoglyphic analyses were carried out on a sample of children with known sex chromosomal aneuploidies (25 XXY, 10 XXX, 1 XXYY). Digital ridge counts and pattern types were determined for each individual. Palm prints and sole patterns were also examined. The results of our study were compared with data from previous studies of sex chromosomal aneuploidies. Our results for the XXY males agree with the findings from other studies with respect to total ridge counts and plantar dermatoglyphics, but not for digital pattern frequencies. Our one example of an XXYY male showed hypothenar patterns similar to those found for this syndrome by other researchers, but neither the digital pattern types nor the unexpectedly high total ridge count conforms to the findings from other studies. Our sample of XXX females falls within the normal XX female range of variation with respect to hypothenar patterns and total ridge count; plantar features show a higher incidence of patterns than previously reported.