The Authors report the eugenic prediction formulated for a couple whose three babies (two of whom were monozygotic twins) had died as a consequence of the syndrome of Werdnig-Hoffmann. Since the two cases of the MZ twin pair represent a single chance combination at conception, and since the indications from the literature and from the family tree in this case indicate a monomeric genotype of a recessive type, the morbid risk for a fourth affected child has been estimated at 25%.

The occurrence of concordant W. H. syndrome in MZ cotwins is stressed.

No chromosome abnormalities have been revealed by karyotype examination of the parents.

Considering the development of the twin method the Authors deem it necessary to review the various systems of analysis presently used. They therefore design a method by which the twin material may be used even when zygosity is unknown. The Authors give this method the name of Azygotic Twin Test (T.G.A.), explain it theoretically and also give a practical example of analysis.

The Authors plan to make - new studies on the subject, in order to show further possible developments of this method.

L'année 1901, trois biologistes, Correns, Tchermak et H. de Vries faisaient, à peu près simultanément, la nouvelle découverte des lois que, trente-cinq ans auparavant, Gregor Mendel avait formulées.

Les soixante ans qui se sont écoulés depuis cette date ont vu se succéder un nombre extraordinaire de découvertes qui ont prodigieusement enrichi l'ensemble de nos connaissances et bouleversé jusqu'à notre conception même de la matière vivante.

Dès le début du siècle, W. Johansenn introduisait la notion de génotype et de phénotype qui précisait l'action respective de l'hérédité et du milieu.

A cette époque, l'aspect particulier que prend le noyau de la cellule au moment de sa division, l'identification des chromosomes, leur forme de bâtonnets, leur colorabilité particulière, tout cela avait été reconnu déjà. Désormais, il était possible de comprendre et d'expliquer les lois mendéliennes de la ségrégation et de la recombinaison. Dès 1903 et 1904, Sutton et Boberi affirmaient que les chromosomes sont les véritables supports de l'hérédité. En 1908, L. Cuénot, expérimentant sur la souris, établissait définitivement que les lois mendéliennes ne s'appliquent pas seulement aux végétaux et aux insectes mais aussi aux mammifères et qu'elles sont des lois générales pour les espèces vivantes.

The Authors confirm the possibility of a discordance between the sex-chromatin of the cells in the breast-carcinoma and that of the cells of a tumour carrier. It is assumed that the somatic mutation giving rise to the formation of the somatic cell might also involve sex-chromatin.

A case of congenital multiple rhabdomyoma of the heart in both of a set of twins of like sex is presented. A separated diamnionic dichorionic placenta was found. However because both twins had the same sex, the same color of eyes, the same blood group and very similar plantar prints pattern they were considered MZ. Twin A died after 10 days becouse of intractable heart failure. Twin B died one hour after birth of hydrops fetalis. The autopsies showed the presence of multiple rabdomyoma in the walls of both hearts and in Twin B a widely patent ductus arteriosus. No other extracardiac anomalies were noted. The diagnosis of rhabdomyoma of the heart, as is usual, was not made. It should be suspected in any infant who shows evidence of cardiac disease. On the other hand, this first case, known so far in the world literature of congenital rhabdomyoma of the heart in both twins could be an important contribution to the knowledge of the nature of this so discussed lesion.

The effect of ionizing radiation, from a 100 Curie Cobalt-60 source, on diploid human cells grown in vitro has been investigated.

The analysed cell populations originated from foetal brain and lung tissue. Other known variations of this material were age and sex of the foetuses, primary and first transfer cultures.

The effect was measured by recording post-metaphase chromosomal aberrations in cell cultures fixed and stained 24 and 48 hours after acute irradiation. “Spontaneous” aberration frequencies were determined in matched control cultures.

Although conclusions must be guarded, in view of the insufficient knowledge of factors influencing human cell populations in vitro, our observations can be summarized, tentatively, in the following main points.

1. The frequency of “spontaneous” aberrations appears to vary with respect to (a) differences between the individuals from whom the biopsies were taken, (b) tissue of origin whether within or between individuals and (c) the sex of the cultured cells.

The qualified estimates of the overall averages of “spontaneous” aberrations were, (a) for the cell cultures derived from foetal lung 0.7 per cent (41/5,891 scored cells) and (b) for the cell cultures derived from foetal brain 2.5 per cent (21/851 scored cells).

2. In the irradiated cell cultures which received doses varying from 9-136 rads of absorbed dose the number of aberrant post-metaphases per 100 cells per rad varied from 0.10-0.15 for cultures derived from lung tissue and from 0.19-0.37 for cultures derived from brain tissue, all at 24 hours after the acute dose. At 48 hours after irradiation the frequencies were somewhat lower but the same trends remained.

3. The cell cultures derived from brain tissue appear to have a higher radio-sensitivity than those derived from lung tissue. Furthermore, a sexual dimorphism is suggested because, in all series of cultures, those composed of XY cells had a higher aberration frequency as compared to those with XX cells.

4. The irradiation doubling dose (for definition, see p. 27) was estimated at 15-40 rads (cf. table 7).

The Authors have investigated by means of the immuno-electrophoretic method the protein composition of the funicular blood of 19 twin-pairs from pregnancies of 5 to 9 months. Monochorionic twins showed a concordant picture, while in 7 of the 14 bichorionic twin-pairs slight differences could be observed, due to the presence in one of the twins of one or two more lines. The Authors put these results in correlation with the hypothesis of a genie control of the production of proteins.

A case of persistent pupillary membrane observed in a mother and in her two monozygotic female twins is reported. The literature on this subject is reviewed.

A pair of male, Negro, fraternal twins are described, both of whom were affected with Rh hemolytic disease. In one twin, the manifestations were typical; jaundice appeared early, exchange transfusion was carried out, and this was followed by prompt and complete recovery. In the second twin, who was treated expectantly, jaundice appeared later and followed the protracted course of the so-called «inspissated bile» syndrome, i. e., the stools were acholic, there was bile in the urine, and most of the serum bilirubin was of the direct reacting type. Of interest was the finding that the occurrence of the syndrome was presaged by the presence of excessive amounts of direct reacting bilirubin in the cord serum. This twin also recovered completely, but convalescence was more prolonged.

The observations on these twins provide further evidence that the constitution of the baby, in addition to the maternal Rh antibody titer determine the nature and severity of the manifestations in an erythroblastotic baby.

The purpose of this first “Round-table Conference” could well be to present the historical development of human genetics from the early days of Mendelism to the elaboration of modern genetic research. The refinement of methodological possibilities and the unfolding of problems indicate to us the proper lines for further study. With this introduction I should like to restrict myself to a few remarks concerning the role of the gene analytical system of Gregor Mendel in human genetics. If as a result of corrent research the concept of the gene has undergone important alterations and is no longer the closed unit of the classical formulation, it still remains a useful concept for practical research. Every investigation of a genetically active factor immediately begins with the determination of a segregating unit or a mutating unit. Determining an allele relationship or a series of multiple alleles will remain the principal result. Quite often in human genetics it has not been possible to demonstrate these relationships as pseudoallelal or with other methods to achieve a differentiation of the gene concept into its subunits: the cistron, recon and muton. So far the objectives of human genetics the employment of the gene concept as classically formulated is methodologically necessary.

The ideal goal of the gene analytical method is to determine the function of all genes which take part in the heredity of an organism, the preparation of theoretical chromosome maps for the various linkage groups, the determination of the relationships between the genes and their alleles to visible or measurable characteristics of the organism, and the establishment of relationships between phenotypic expression and dominance or epistasis. Its further area of interest is in the genetic analysis of natural populations, the question of spontaneous mutability, the problem of genetic diversity and the polymorphism caused by it in populations, and the equilibrium between all alleles. These questions lead necessarily to general problems of population dynamics, adaptation and evolution.

La limitazione del tempo messo a mia disposizione, mi impedisce di illustrare le varie tappe della genetica, intesa come scienza morfologico-descrittiva. Dallo studio delle cellule germinali siamo passati via via a quello dei cromosomi, dei geni, dei loci. A sua volta il gene è stato suddiviso in varie unità indipendenti (muton, recon, cistron). Ma un importante passo avanti è stato compiuto soltanto quando lo studio è stato affrontato dai biochimici, i quali hanno dimostrato che le variazioni strutturali della complessa molecola dell'acido desossiribonucleico (D.N.A.) bastano a spiegare l'enorme molteplicità dei geni, e le loro possibili mutazioni.

Grazie alle scoperte della biochimica noi siamo così passati dallo studio dell'eredità cromosomica e genica a quello dell'eredità molecolare.

Bisogna riconoscere che, in questo campo, i clinici hanno precorso i genetisti ed i biochimici. Spetta infatti al medico inglese Archibald Garrod (1902) il grande merito di avere per primo espresso il concetto che una malattia ereditaria può dipendere da una turba metabolica dipendente da un errore nella sintesi di una molecola proteica. Egli partì dall'esempio della alcaptonuria, alla quale malattia altre ne aggiunse, riunendole nel gruppo degli «inborn errors of metabolism». Questo concetto è stato in seguito allargato, ed anzi alcuni genetisti (Pauling) sostengono che tutte le malattie ereditarie sono dovute a formazione di molecole anormali. Altri autori invece restringono il concetto alle sole malattie nelle quali sono state effettivamente dimostrate mutazioni nella struttura molecolare (come per es. le emoglobinopatie). Io ritengo che convenga scartare sia la defmizione troppo allargata che quella troppo ristretta e di ritenerci autorizzati a parlare di «sindromi molecolari» quando noi ci troviamo di fronte ad una malattia in cui si possa dimostrare o per lo meno presumere che l'alterazione caratteristica risieda a livello di una singola o di più molecole.

The A. has studied 51 pairs of epileptic twins: 20 were MZ (11 ♂, 9 ♀) and 31 DZ (9 ♂ 12 ♀, ♂♀).

An ereditary aetiology has been found in 65% of cases:

a) by the concordance of 80% of MZ against 35% of DZ. The MZ concordant in the symptomatic form were 62,5% the DZ 14, 5% the MZ concordant in the so-called idiopathic form were 91%, the DZ 50%.

b) by the incidence in one third of the families of a relative with epileptic seizures (3-4,7% against the 0,5% of general population).

Genic information is not specific either for the convulsive form nor for the electroencephalografic dysrythmia which are only some of the phenotypic manifestations of a deeper disturbance. The pathologic gene or genes should act at a metabolic level with a pleiotropic action upon more functions of the nervous system. The genetic action of the major gene is that of an autosomic, dominant one.

Data obtained from 53 Panjabi Khatris families were tested for mode of inheritance of patterns on palmar interdigital area II. Gene frequencies were obtained from 1,000 unselected Panjabi Khatris.

Analysis of the data indicate that a single dominant gene, with approximately 88% penetrance, is responsible for D patterns in both the second and fourth interdigital areas of the palm.

The incidence of pterygium was studied in an isolated highly inbred fisher population. A clinical and hematological examination was performed and the blood chemistry was studied. Genealogical tables (pedigrees) were prepared for all probands and the degree of consanguinity in their parents stated. Of the total of 479 subjects studied by random sampling, 19 (4 per cent) had pterygium with a relatively high manifestation age. No linkage was detected between the genes for the blood group systems, serum groups etc. and the gene for pterygium. Increased capillary fragility was established in 10 probands. Capillary permeability was studied in 2 probands by the concentration in the anterior chamber of intravenously administrated fluorescein, and the test was found to be weakly pathological in one of them. The serum cholesterol level was elevated in 5 of the patients studied. Ophthalmological examination indicated the accumulation of degenerative eye diseases. Pingueculum showed a more pronounced development in 10 of the 17 subjects examined than in the rest of the population. The possibility of recessive transmission of the hereditary predisposition is discussed with reference to the high frequency of inbreeding and the accumulation of pterygium within the isolated population. According to the special frequency-raising peristasis conditions in an outer archipelago community and to the mendelian segregation rate, a not sex-linked, simple dominant gene, with low penetrance and no selective disadvantage for the pterygium seems to be the most plausible explanation. Because of the late manifestation age, pterygium was observed only in 2 generations. The expressiveness of the gene was unsteady and asymmetry of pterygium in the eyes of the probands is not uncommon.

The relation between stature and parental birth-place was studied in samples of Swedish conscripts from three different geographical areas. In North Sweden conscripts with both parents born in the same parish have a significantly lower average stature than conscripts with parents born in different parishes. In Central Sweden the reversed picture was found and in South Sweden no significant difference was found.

Ce sont des recherches effectuées sur les bactéries et les bactériophages qui ont apporté la preuve formelle du rôle génétique des acides désoxyribonucléiques (ADN): parmi les nombreux faits qui démontrent ce rôle, il faut surtout citer les transformations bactériennes (Avery) et l'expérience de la «seringue» de Hershey. Dans le premier cas, l'addition à une souche bactériennea d'un ADN spécifique, isolé à partir d'un mutantb, transmet la mutationb, dans un pourcentage élevé des cas, à la descendance; le caractère ainsi acquis se maintient héréditairement. Pour que la transformation s'obtienne, il faut, évidemment, que l'ADN transformant puisse pénétrer dans les bactériesa et s'incorporer dans leur génome. Quant à l'expérience de Hershey, où un double marquage au 35S et au 32P servait à suivre le sort des protéines et celui de l'ADN lors de l'infection de bactéries par des phages, elle a permis de montrer que ces derniers se comportent comme une «seringue» qui injecte la totalité de l'ADN dans la bactérie infectée; en effet, la pénétration des protéines dans ces bactéries est négligeable par rapport à celle de l'ADN. Cette injection d'ADN a pour conséquence la production de particules de phages complètes, présentant les caractéristiques génétiques exactes du phage dont l'ADN provenait.

Two familial cases (father and son) of Addison disease, occurred after « asian influenza », are reported.

Clinical data suggest tat the pathological basis for adrenal insufficiency could be the so-called « simple fibrosclerosis » and that virus infection has acted as a precipitating factor of an underlying adrenal meyopragy, since both patients as well as other members of the same familyi have a hyperpigmentated skin.

The two patients have shown a Addison syndrome « partially compensate » with incomplete symptomatology for lack of functional adrenal reserve which has been detected only by ACTH stimulation (which was inefficient).

As far as we know, this is the first report of a chronic hypercorticalism occurred in the father and one of his sons.