Mosaic supernumerary r(1)(p13.2q23.3) in a 10-year-old girl with epilepsy facial asymmetry psychomotor retardation kyphoscoliosis dermatofibrosarcoma and multiple exostoses

We report molecular cytogenetic characterization of mosaic supernumerary r(1)(p13.2q23.3) in a 10-year-old girl with epilepsy, facial asymmetry, psychomotor retardation, kyphoscoliosis, dermatofibrosarcoma and multiple exostoses. The supernumerary r(1) is associated with gene dosage increase of CHRNB2, ADAR and KCNJ10 in the pericentromeric area of 1q, and a breakpoint within CTTNBP2NL at 1p13.2. We speculate that the gene dosage increase of CHRNB2, ADAR and KCNJ10 is most likely responsible for epilepsy, and the breakpoint at 1p13.2 in the supernumerary r(1) is most likely responsible for the development of multiple exostoses and osteochondroma in this patient.     

The r(14) syndrome. 3 new observations

Three observations of r(14) are reported. Constant features of r(14) syndrome are the following: moderate but typical craniofacial dysmorphism, seizures and other neurological abnormalities, abnormal retinal pigmentation, and recurrent respiratory infections. The value of gene dosage evaluation for genes mapped to the distal segment of 14q, particularly the Ig heavy chain genes, is emphasized.     

Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene

Allan-Herndon-Dudley syndrome was among the first of the X-linked mental retardation syndromes to be described (in 1944) and among the first to be regionally mapped on the X chromosome (in 1990). Six large families with the syndrome have been identified, and linkage studies have placed the gene locus in Xq13.2. Mutations in the monocarboxylate transporter 8 gene (MCT8) have been found in each of the six families. One essential function of the protein encoded by this gene appears to be the transport of triiodothyronine into neurons. Abnormal transporter function is reflected in elevated free triiodothyronine and lowered free thyroxine levels in the blood. Infancy and childhood in the Allan-Herndon-Dudley syndrome are marked by hypotonia, weakness, reduced muscle mass, and delay of developmental milestones. Facial manifestations are not distinctive, but the face tends to be elongated with bifrontal narrowing, and the ears are often simply formed or cupped. Some patients have myopathic facies. Generalized weakness is manifested by excessive drooling, forward positioning of the head and neck, failure to ambulate independently, or ataxia in those who do ambulate. Speech is dysarthric or absent altogether. Hypotonia gives way in adult life to spasticity. The hands exhibit dystonic and athetoid posturing and fisting. Cognitive development is severely impaired. No major malformations occur, intrauterine growth is not impaired, and head circumference and genital development are usually normal. Behavior tends to be passive, with little evidence of aggressive or disruptive behavior. Although clinical signs of thyroid dysfunction are usually absent in affected males, the disturbances in blood levels of thyroid hormones suggest the possibility of systematic detection through screening of high-risk populations.     

A case of r(21) with stigmata of atypical Down syndrome

Summary A case of r(21) with stigmata of atypical Down syndrome is presented. Karyotype of the proposita was determined as 45,XX,-21/46,XX,-21, +r(21)/47,XX,-21,+r(21),+(21). Most ring chromosomes showed double-sized ring chromosomes, which were trisomic for 21p11-21q22.3 and monosomic for 21q22.3-qter. SOD-1 activity revealed only slight elevation. The mechanism of ring formation is discussed.     

Parallel polymorphism for supernumerary segments inChorthippus parallelus (zetterstedt)

A complex and parallel pattern of polymorphism for heterochromatic supernumerary segments in the M₇ and S₈ chromosomes has been found in 14 populations of the meadow grasshopperChorthippus parallelus. Nine distinct karyotype classes for these two chromosome pairs occur though they are not equally represented in different populations. Populations differ also with respect to the frequency of supernumerary segments they contain. In all populations the presence of supernumerary segments leads to a significant elevation of mean cell chiasma frequency compared to individuals from the same population lacking such segments. The extent of the effect appears to differ in different populations. The observed frequencies of S₈ karyotypes conform to the expectations of a Hardy-Weinberg distribution. Those of the M₇, however, do not, and in all but one of the 14 populations there is a significant excess of homokaryotypes. In the Ashurst population 26% of the individuals sampled were characterised by germ-line polysomy for the M₄ chromosome, either in the form of entire tetrasomics or more usually as mosaics ranging from tri- to hepta-somics. In all these polysomics the M₄ chromosomes in excess of two were regularly heteropycnotic at first meiotic prophase from zygotene to diakinesis. As a consequence of this multivalents are rare. Extra M₄ chromosomes do not modify the chiasma characteristics of the other chromosomes in the complement. Nor do they modify the action of the supernumerary segments in any way.     

Crystal structure of a left-handed RNA tetramer, r(C-br8G)2

The crystal structure of the modified RNA tetramer, r(C-br8G-C-br8G), was determined by x-ray methods. The crystals are trigonal and belong to the space group P3212. There are three independent tetramers in the unit cell and each forms a left-handed duplex similar to Z-DNA regarding the orientations of the base moiety and the sugar puckerings in guanosine and cytidine. The effect of the additional bromine atom and 2'-hydroxy group on the stabilization of the Z-form structure are also described.     

Parallel polymorphism for supernumerary segments in Chorthippus parallelus (Zetterstedt)

Heterochromatic supernumerary segments, present in either or both the M₇ and the S₈ chromosomes of the Ashurst (AS) population of Chorthippus parallelus, lead to a significant elevation in mean cell chiasma frequency. This effect appears to be dosage independent within both the S₈ and the M₇ karyomorphs when these are considered separately. Neither is there any marked interaction between the two systems when they are combined with one another. The selective factors controlling the distribution of S₈ karyomorphs within the population appear, however, to act quite independently of those which regulate the M₇ karyomorph pattern. This is revealed in two ways. First, whereas the frequency of S₈ karyomorphs conform to the expectations of a Hardy-Weinberg distribution those of the M₇ do not. Secondly, though the pattern of distribution of S₈ types is uniform throughout the AS population that of the M₇ is not. This heterogeneity of M₇ karyomorphs implies that the population is in some way internally stratified in terms of its breeding structure.     

Parallel polymorphism for supernumerary segments in Chorthippus parallelus (Zetterstedt)

French populations of Chorthippus parallelus like those from Britain are polymorphic with respect to supernumerary segments on the M₇ and S₈ chromosomes. The pattern of polymorphism parallels that of British material on both morphological and behavioural grounds. It agrees also in its effect on mean cell chiasma frequency and the absence of any effect on between cell variance. Finally the agreement extends also to the distribution of karyotypes within populations, those of the S₈ showing a Hardy-Weinberg distribution whereas those of the M₇ show a deficiency of structurally heterozygous types. All these parallels imply a common origin for the British and French material, an origin which, so we must suppose, antedated the physical separation of Britain and France some 8,000 years ago.     

Germ line-restricted supernumerary (B) chromosomes in Eptatretus okinoseanus.

Cytogenetic studies were performed on two types of Japanese hagfish (Eptatretus okinoseanus) that eliminate about 45% (type A) and 55% (type B) of their DNA from presumptive somatic cells during the differentiation of somatic cells. The observations revealed inter- and intraindividual variations in the number of chromosomes in germ cells of both types of hagfishes. Although the modal number of chromosomes in the germ cells was 54 in both types, the percentage of cells with the modal number was rather low (38.6% [51/132] in five specimens of type A and 22.7% [25/110] in eight specimens of type B). In addition, one of seven type B specimens clearly had a modal number of 62 chromosomes. Another specimen of type B had a bimodal distribution of chromosome numbers, with peaks of 54 and 59 chromosomes. The observation of interindividual variations was supported by data on the amount of DNA in germ cells of type B specimens. However, these variations were rarely observed in somatic cells. These results suggest that supernumerary (B) chromosomes are maintained in germ cells and are eliminated together with some other chromosomes and/or chromatin from somatic cells.     

Parallel polymorphism for supernumerary segments in Chorthippus parallelus (Zetterstedt)

Karyomorph comparisons within the Ashurst population during 1968 give evidence both of a temporal and a spatial distribution within the population. The former is seen with respect to the distribution of M₇ karyomorphs which show a Hardy-Weinberg pattern in the earliest collection but not at other times. The latter is revealed in the distinctive character of the B-site sample where the basic homozygous and the heterozygous S₈ karyomorphs approximate more closely in frequency than at any other site. Individuals polysomic for the M₄ chromosome have been recovered from the population over three successive years of sampling and confer a distinctive karyological structure on it.     

Silver staining of the supernumerary chromosome in the cat-eye syndrome

A case of the Cat-eye syndrome (CES) with 47,YX, + mar is presented. Silver staining method revealed the marker chromosome to be bisatellited. This abnormal chromosome is interpreted as the product of a Robertsonian translocation between the short arm and satellites of chromosome 22 and short arm of another D-group chromosome, probably No. 13.