A number of patients with retinoblastoma have a deletion of chromosome 13. Comparison of the deleted segments from different individuals reveals that all deletions involve chromosome band 13q 14. This observation has lead to the hypothesis that in this region is a gene or genes important in the etiology of retinoblastoma. As a first step toward understanding those genes, the authors successfully isolated five DNA fragments from chromosome 13 using recombinant DNA techniques. The DNA fragments from chromosome 13 will be useful in identifying DNA polymorphic sites that are linked to the retinoblastoma locus tentatively assigned to 13q 14. Such DNA polymorphisms will be important in the genetic counselling of families with retinoblastoma. These chromosome 13q 14 fragments also may be useful in searching for microdeletions of 13q14.

A 6-year-old mentally retarded child presented with a clinical picture consistent with the diagnosis of childhood autism. Chromosomal studies revealed a male karyotype with approximately 11% of the cells counted containing a fragile site on the X chromosome. The possibility of a syndrome of autism occurring in children with the Fragile-X syndrome is discussed.

We have utilized the methods of Gusella et al (PNAS 77, 2829, 1980) to isolate DNA segments from the human X chromosome. DNA was prepared from a human-Chinese hamster hybrid cell line containing the human X and essentially no other human chromosome. This DNA was ligated to phage DNA, the recombinant phage encapsulated and grown in E.coli. The plaques were exposed to labelled whole human and Chinese hamster DNA. Plaques which did not anneal with Chinese hamster DNA but did anneal with human DNA were isolated. The human DNA segments were recovered from these selected recombinant phage and tested for their ability to anneal with DNA from hybrid cells containing various human chromosomes. Six different recombinant phage have been studied sufficiently to demonstrate that they contain human DNA which is complementary to the human X and apparently to no other human chromosome. Further studies with hybrid cells containing known portions of the human X indicate that the recombinant DNA segments are derived from specific regions of the X. The methods utilized are efficient and demonstrate the feasibility of isolating a large number of DNA segments from the human X. These segments are suitable for detecting DNA polymorphisms and for study of X chromosome inactivation. (Presented in part to the Association for Research in Nervous and Mental Disease, December 5, 1980.)

Previous studies of XXY boys from biased sources of ascertainment have suggested a risk for communication disorders, and ongoing longitudinal prospective studies of unselected XXY boys have demonstrated early lags in speech development. This study compares the communication skills of a group of 14 unselected XXY boys ascertained during a neonatal screening survey with a group of 15 normal control boys, matched for age, grade, performance IQ, birth weight, parental age and education, parity and socioeconomic status. Although the XXY group did not significantly differ from the control group in performance IQ, they did demonstrate a significant reduction in verbal IQ (p≤0.001), which resulted in a reduced full scale IQ (p≤0.01). The reduction in verbal IQ was correlated with significant reductions in auditory processing abilities, auditory memory, and expressive language. Of particular interest was the demonstration of word-finding difficulties and problems in the use of syntax as major factors in the expressive language deficit. Except for difficulties with syntax, receptive language skills were relatively normal. These results suggest that left-hemisphere-based difficulty in serial order processing may be associated with the XXY anomaly, as compared with right-hemisphere deficits in spatial processing that have been associated with XO Turner syndrome.

Previous studies of XXY boys from biased sources of ascertainment have suggested a risk for communication disorders, and ongoing longitudinal prospective studies of unselected XXY boys have demonstrated early lags in speech development. This study compares the communication skills of a group of 14 unselected XXY boys ascertained during a neonatal screening survey with a group of 15 normal control boys, matched for age, grade, performance IQ, birth weight, parental age and education, parity and socioeconomic status. Although the XXY group did not significantly differ from the control group in performance IQ, they did demonstrate a significant reduction in verbal IQ (p≤0.001), which resulted in a reduced full scale IQ (p≤0.01). The reduction in verbal IQ was correlated with significant reductions in auditory processing abilities, auditory memory, and expressive language. Of particular interest was the demonstration of word-finding difficulties and problems in the use of syntax as major factors in the expressive language deficit. Except for difficulties with syntax, receptive language skills were relatively normal. These results suggest that left-hemisphere-based difficulty in serial order processing may be associated with the XXY anomaly, as compared with right-hemisphere deficits in spatial processing that have been associated with XO Turner syndrome.

This issue of the Journal contains an article by Turner and her colleagues that presents yet another chapter in the rapidly expanding saga of the relation between mental retardation and a cytogenetically detectable change in the X chromosome. The story begins with Penrose's report in 1938 of an excess of males among persons who are institutionalized because of mental retardation.1 The excess has been repeatedly confirmed since then and has been shown to be quite large: there are often 30 to 50 per cent more men than women. In 1974, Gillian Turner and her husband examined the records of all . . .

Detailed ultrastructural analysis of the respiratory cilia of three male patients with the immotile-cilia syndrome is presented. They all had similar clinical manifestations, namely, situs inversus totalis, repeated respiratory infections, and sinusitis. The respiratory cilia, however, of these patients showed a variety of structural abnormalities some of which are described for the first time. In the cilia of the first patient both the dynein arms were lacking, and, almost 40% of the cilia had one to nine supernumerary microtubules peripheral to the nine outer doublets. The cilia of the second patient showed an absence of inner dynein arms, unusually prominent outer dynein arms, a spoke defect in 46% of cilia examined, and no morphologically detectable nexin links. The cilia of the last patient lacked both dynein arms but, in contrast to the first two patients, showed virtually no microtubular abnormalities. These patients demonstrate that a variety of structural abnormalities in respiratory cilia can result in virtually identical clinical manifestations.

The aberrations of the male gonads and genitalia range from such common entities as hypospadias and undescended testes to rare and bizarre disorders like hermaphroditism. As is often the case, the cause of the more common disorders has proved to be elusive, but some insight into the rarer entities is being attained from studies of the H-Y antigen. A case in point is the study by Winters and his colleagues in this issue of the Journal. Cases of this kind are worthy of close observation in the hope that the resolution of the rare end of the spectrum of . . .

Kartagener's syndrome [situs inversus totalis (SIT), bronchiectasis and sinusitis] has been shown by others to have morphologically abnormal sperm tails and cilia, evidenced by absence of dynein arms. We used brush biopsies of the nasopharynx under local anesthesia for the study of ciliary morphology by EM in 9 patients with dextrocardia. Three of these have SIT and recurrent respiratory disease. One SIT lacks dynein arms and is a typical Kartagener's syndrome. A second SIT has abnormal (thickened and knobby) outer dynein arms in all cilia. This may be a new type of Kartagener's syndrome. The third SIT has normal dynein arms and some features of cystic fibrosis (CF), with intermittently elevated sweat sodium. The cultured fibroblasts of this patient do not show a CF-like response to ouabain, suggesting that this may not be CF. Of the 6 dextrocardiacs without SIT, all have normal dynein arms except one. In this patient (with L-TGA and without respiratory disease), the outer dynein arms are abnormally positioned in all cilia. We propose that dynein arm abnormalities may be an etiologic factor in a significant fraction of cardiac malrotations.

Chinese hamster × mouse hybrid cells segregating mouse chromosomes have been used to assign a gene for triosephosphate isomerase (TPI-1, EC 5.3.1.1, McKusick #19045) to mouse chromosome 6, and a gene for Glyoxalase-I (GLO-1, EC4.4.1.5, McKusick #13875) to mouse chromosome 17. The genes for TPI-1 and lactate dehydrogenase B are syntenic in man and probably so in the dog. It is therefore likely that they are syntenic also in the mouse. It is of interest then that there is a mouse gene,Ldr-1, on chromosome 6 that regulates the level of LDH B subunits in mouse erythrocytes. The locus for GLO-1 is closely linked to the major histocompatibility complex in man. Since the major histocompatibility complex in the mouse is present on chromosome 17, this locus and theGlo-1 locus are syntenic in the mouse as well. This finding adds to the number of autosomal gene pairs which are syntenic in both mouse and man and reinforces the belief that there is considerable conservation of linkage groups during evolution.

Philip Reilly is a young, articulate law graduate from Columbia University who studied human genetics for several years under Margery Shaw. (Margery Shaw herself obtained a law degree after first achieving a national reputation as a human geneticist.) Reilly thus brings an unusual combination of talents to the writing of this book. No detailed preface is provided to indicate the intended audience, but it is easy to imagine that all those interested in the conjunction of fields included in the title will find the material worth reading. As might be expected from the author's beginnings, the treatment of the topics emphasizes the legal more than the medical and genetic aspects. In keeping with this, the first chapter includes some elementary explanations of genetics that will be more helpful to lawyers and legislators than to physicians. The remainder of the book examines in roughly equally parts genetic screening legislation and the

Two types of alpha-D-mannosidase isozymes are present in human white blood cells, human diploid fibroblasts, and HeLa cells. One of these (the S isozyme) constitutes the major alpha-D-mannosidase of the human cells, has a pH optimum of 4.4, and is associated with lysosomes. The other (the F isozyme) is most active at pH 6, is acid labile, and is located in the soluble portion of the cytoplasm. The expression of human lysosomal alpha-D-mannosidase was examined in man-hamster hybrid clones, and was found to be concordant with that of phosphohexose isomerase in 54 of 55 primary clones. A locus specifying human lysosomal alpha-D-mannosidase has therfore been assigned to chromosome 19.

Modifications in the techniques for the induction of mammalian somatic cell hybridization by polyethylene glycol (PEG) have led to procedures that are rapid, simple, and effective. The basic improvements, for both monolayer and suspension fusions, are a short exposure to PEG and a rapid dilution of PEG following treatment. There is a marked effect of PEG concentration on cell hybridization, and there seem to be inherent differences between cells in terms of the extent of cell fusion induced by PEG.

BrdU-33258 Hoechst techniques have been used to characterize DNA replication patterns in lymphocytes from human females with supernumerary or structurally abnormal X chromosomes. Fluorescence analysis permits identification of late replicating X chromosomes in a very high proportion of cells and affords a high resolution method for determining the interchange points of X-X and X-autosome translocations. Asynchrony among terminal replication patterns of multiple late replicating X chromosomes within an individual cell can occasionally be demonstrated. The arms of isochromosomes usually exhibit symmetrical fluorescence patterns, with replication terminating in bands Xq21 and Xq23 (predominant pattern) or in bands Xq25 and Xq27 (alternative pattern) in both arms. In the vast majority of lymphocytes containing a balanced X-13 or X-19 translocation, the normal X is late replicating. However, DNA synthesis in the translocation products occasionally appears somewhat delayed relative to that expected for an early replicating X, consistent with possible position effects on replication kinetics.

The malarial parasite must enter the erythrocyte of its host before it is able to undergo multiplication. In the absence of this replicative step, malarial infection would be a trivial, self-limited condition. Invasion of the erythrocyte is obviously a key step in this process and presumably involves more than mere mechanical penetration, since the membrane is intact afterward. In keeping with these notions, Miller and his co-workers have now shown that infection of the red cell by several species of malaria is apparently dependent upon a specific membrane factor either dictated by or genetically associated with the Duffy blood group. . . .

The expression of the adenylate kinase isozymes and of phosphopyruvate hydratase was studied in man-mouse and man-hamster hybrid clones. Concordant segregation of the loci coding for AK-2 and PPH was observed in 54 of 55 primary hybrid clones, and these loci were demonstrated to be synthetic with the loci specifying PGM-1 and PGD. The pattern of expression of the four enzymes in discordant clones suggests the gene order 1pter-(PGD,PPH)-AK-2-PGM-1-centromere. In addition, AK-1 was found to be expressed independently of AK-2.