Biomedical subjects
Publications and source records attributed to M Moller.
A 3.5-year-old boy with a de novo tandem duplication 5q11.1----5q15 is reported. Since the physical stigmata of seven liveborn cases with 5q proximal duplications are variable and inconspicuous, a recognizable syndrome could not be delineated. On the contrary, the associated developmental delay seems to be severe in duplications extending into 5q22 and mild in duplications 5q11----q13.
A family with three brothers presenting 12p trisomy due to an adjacent-1 segregation of a paternal translocation (1;12) (q44;p12.2) is described. The patient's phenotype was compatible with the chromosomal imbalance including the gene dosage effect of the glyceraldehyde-3-phosphate dehydrogenase. The importance of the genetic counseling in these families is stressed.
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The T3 concentration in brain predominantly reflects local production from T4 rather than T3 uptake from the circulating pool. We recently demonstrated that rat brain T3 content is increased by glucose feeding compared to chow feeding. One possible mechanism for this effect is an increase in brain T4 5'-deiodinase (5'-D) activity. Our recent preliminary studies of neuroblastoma (NB) cells demonstrate that renewal of RPMI-1640 medium stimulates T4 5'-D type II (NB T4 5'-D II) activity in these cells. The present studies were performed to determine the mechanism of this response. Studies were performed on NB cells supported in thyroid hormone-depleted (deficient) medium. This approach increased NB T4 5'-DII activity 4-fold compared to that in thyroid hormone-replete medium. Medium renewal further stimulated enzyme activity (7- to 9-fold; maximum at 6 h) in each group. The difference between the hypothyroid group and control was sustained over a 24-h period. Subsequent studies demonstrated that glucose (11 mM) was the specific medium ingredient mediating the medium renewal response. A progressive increase in NB T4 5'-DII activity was noted over 8 h during RPMI-1640 salt plus glucose (11 mM) incubation. This was equivalent to the effect of complete medium containing glucose (11 mM). Coincubation with insulin (10(-7)-10(-9) M) did not modify the enzyme response to glucose. In addition, fructose (10 mM) had a similar effect on enzyme activity. Glycerol and essential and nonessential amino acids also modestly increased NB T4 5'-DII activity compared to that in the control group (P less than 0.01). Actinomycin-D (1 microM), cycloheximide (100 microM), and puromycin (100 microM) significantly (P less than 0.001) decreased the glucose effect on T4 5'-DII by 5-, 9-, and 17-fold, respectively, after 6 h of incubation. In addition, puromycin (10-200 microM) inhibited both NB T4 5'-DII activity and [3H]amino acid incorporation during incubation in glucose. There was a significant correlation between these parameters (r = 0.8; P less than 0.001). The enzyme activity decay curves in the glucose-activated and control groups subsequent to puromycin (100 microM) addition at 8 h were parallel. The fractional turnover rate was 13%/h in the controls and 11%/h in the glucose groups. The calculated enzyme production rate was significantly higher (P less than 0.005) in the glucose group compared to that in the control group (17.4 vs. 6.8 fmol/mg protein.h).(ABSTRACT TRUNCATED AT 400 WORDS)
A 24-year-old female with a Swyer syndrome phenotype was found to have a 46,X,del (Y) (p11) karyotype. This observation is consistent with the recently confirmed assignment of the testis-determining master gene to the deletion interval 1A of the Y (Page et al., 1987). Otherwise, it illustrates the etiological heterogeneity of the Swyer phenotype and allows to emphasize the de novo origin of XYp-females.
A 4-month-old male infant with muscular hypotonia, growth and psychomotor retardation, large low-set ears, hypoplastic genitalia, right hip luxation and bilateral equinovarus, was found to have a constitutional 46,XY,del(5)(q23.3q31.1) karyotype. From the comparison with 12 similar cases, a rather characteristic clinical phenotype emerges.
A 17-year-old female patient with gonadal dysgenesis but no other turnerian features was found to have a 46,X,idic(X)(pter----q2803:q2803----pter) karyotype in her lymphocytes. Replication of the rearranged X was consistently late and symmetrical. It is postulated that the ovarian dysgenesis usually seen in nonmosaic carriers of Xq;Xq terminal rearrangements may be secondary to a nonreactivation of the abnormal chromosome before meiosis.
A 4 1/2 years old boy was found to have hypoplasia of the pectoralis major right muscle and a karyotype 46,XY,inv(5)(p13q13)mat. This inversion, probably independent of the boy's malformation, was present in at least four generations and it seems neither to impair fertility nor to yield viable recombinants.
A 7 7/12-year-old girl with a de novo deletion 4p15.32----pter without the typical Wolf-Hirschhorn syndrome (WHS) is presented. This observation and others from medical literature suggest that monosomy 4p15.31----4p15.32, rather than 4p16, is the cause of the typical WHS.
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A syndrome of piebaldism and mild to moderate mental retardation was present in 3 sibs and their father. Besides, the disorder was segregating concordantly with a t(1;2) (p22.1;q36). It is concluded that the syndrome is due, either by gene breakage or dysfunction, to the translocation.
An infant deceased at 2 months of age was found to have a 46,XY,-10, +der(10),t (6;10) (q23;q26) mat karyotype. Since the clinical findings were similar to those of the trisomy 6qter syndrome, the present observation agrees with the assignment of the 6q23----qter segment as the pathogenetic determiner of this entity.
Two unrelated patients with monosomy 13q32.3----qter are reported. Comparison with six similar cases previously published indicates that the craniofacial dysmorphism of the 13qter monosomy syndrome is related to band 13q34, the thumb hypoplasia to band 13q32, and an apparently different phenotype to band 13q33. Coagulation deficiency appears to be non-specific in monosomy 13qter.
A female infant with partial trisomy 3p and a terminal deletion 12p, due to a paternal (3;12)(p25.1;p13.31) translocation is described. Normal glyceraldehyde-3-phosphate (GAPD) activity in the proposita tentatively excludes GAPD locus from the deleted segment. Therefore, the region for this locus is reduced to 12p13.1----p13.31.
A 4 4/12 year-old girl with a peculiar phenotype due to a 46,XX/46,XX, dir dup(7)(p1300----p2200) karyotype is described. The comparison with about ten similar cases permitted a better delineation of the 7p trisomy syndrome and the assignment of the band 7p21 as the critical one. Mechanisms for the origin of homogeneous and mosaic duplications, including one model based on a meiotic half chromatid duplication, are discussed.
A hitherto undescribed inv(2) (p2300q11.2) was found in 2 generations of a family ascertained through a holoprosencephalic liveborn boy with normal karyotype. This inversion, quite probably not related to the child malformations, does not seem neither impair reproductive fitness nor to yield viable recombination aneusomies.
An inv(1) (p3500q21.3) was found in an azoospermic man, his mother and two other maternal relatives. Although the mechanisms involved are still unclear, it is stressed that pericentric inversions of chromosome 1 in which the inverted chromosome becomes submetacentric (centromeric index less than or equal to 0.324) apparently impair spermatogenesis.
An inv ins(7;2)(q21.2;q3105q24.2) was found to segregate through four generations of a family. Adjacent-1 segregation aneusomies were ascertained in five patients: three monosomics and two trisomics; and the corresponding syndromes were delineated. The comparative analysis between these and other previously described 2q aneusomic individuals led to the conclusion that a large cleft between first and second toes is a constant feature in monosomy 2q24----q31. No other trait could plausibly be mapped. Risks of 7.9 to 31.6% for aneusomic children and of 26.3% for abortion were estimated in the present family.