The Authors have studied the erythrocytometric curve in twins using for comparison the Price-Jones' index for the evaluation of long term-findings in the same healthy subject. The upper limit of such an index is = 3. The monozygotic twins show curves which, when statistically analized, behave just as curves of the same subject. When the index values are over such a limit, a discordant disease — i. e. a disease present only in a twin — is usually observed. These findings may be explained by admitting that the diameter of erythrocytes represents a hereditary trait conditioned by the genotype.

The complex serologic behavior of the Rh-Hr agglutinogens has been underlined by the recent discovery that, with very rare exceptions, associated with blood factor Rh0 of Rh-positive blood, there are numerous other blood factors which we designated RhA, RhB, RhC. Rare Rh-positive individuals exist whose bloods have blood factor Rh0 but lack one or more of the other components. Such individuals can and have become sensitized to the missing blood factor. For example, in the case of an Rh-positive individual lacking blood factor RhA, anti-RhA may be produced. So, too, when RhB and RhC, are lacking, anti-RhB or anti-RhC may be produced. In fact, all 3 have been identified. The resulting anti-RhA, anti-RhB and anti-RhC serums are indistinguishable from “standard” anti-Rh0 serum in parallel tests on a random series of blood specimens, unless the series happens to include one of the rare Rh-positive bloods lacking blood factor RhA (type Rh0a or type Rh1a, etc.).

In the present paper, anti-RhA serum from a sensitized type Rh1a mother whose child had erythroblastosis was used for studies on the distribution and heredity of the RhA blood factor. In addition, attention is called to the fact that Unger and Wiener have identified anti-RhB and anti-RhC although they are reporting at this time their studies with anti-RhA. A total of 2012 blood specimens from Rh0-positive individuals were tested; 951 from Caucasoids and 918 from Negroids. In tests on blood from Caucasoids, a “standard” Rh0 blood factor was invariably associated with a “standard” RhA blood factor. In no instance where the reactions with anti-Rh0 serums were typical was the RhA factor absent or a variant. However, if the Rh0 factor was a variant, 3 possibilities with regard to factor RhA were identified. Either factor RhA was “standard”, or factor RhA was a variant, or factor RhA was absent. This last possibility rarely occurs in Caucasoids since in our series only 1 Caucasoid blood or 0.1 percent lacked RhA blood factor and in that case the Rh0 factor was a variant.

Among the 918 Rh-positive blood specimens from Negroids examined the situation was found to be somewhat different. While a “standard” Rh0, was almost always associated with a “standard” RhA, in 0.9 percent the RhA factor was absent. Among bloods with a Rh0 variant blood factor, just as with Caucasoids, all 3 possibilities were identified, namely bloods with “standard” RhA, with RhA variant, and also bloods with blood factor RhA absent. The incidence of Rh-positive bloods lacking factor RhA was considerably higher among Negroids than among Caucasoids, namely, 1.6 percent in Negroids, as compared with only 0.1 percent in Caucasoids.

One interesting family was studied. The father's blood had the “standard” Rh0 blood factor, but lacked the RhA component (type Rh0a). The mother's blood had the Rh0 variant blood factor, and also lacked blood factor RhA (type ). The child's blood was of the same type as its mother, namely, Rh0 variant and lacking blood factor RhA (type ). The possible genetic explanations for these observations and their clinical significance were discussed.

The Author reports on genetic problems of blood coagulation. Recent haematological reports on haemophilia, as for instance the differentiation of haemophilia into two different types (haemophilia A and B) bring up the question of the interrelations lig between the two genes responsible for the two types. The problem of recognizing female carriers is mentioned as well as the question of existence of female hemoghilian. It is pointed to further recent haemorrhagic diathese of genetic importance, PTA deficiency as well as the Hageman factor deficiency. Comprehensive investigations of factor VII deficiency on families, in Switzerland are of special genetic interest. These investigations have shown, that in those families, patients with complete deficiency of these factors are found, as well as members of the family not showing any haemorrhagic tendency being in complete health, but a quantitative deficiency of factor VII or Stuart-Power factor can be proved. A third group of members of these families is known to be healthy, showing a normal level of these coagulation factors. Healthy persons with a certain deficiency of factor VII or Stuart-Power factor can be regarded as heterozygotes.

The heredity investigation on thrombopathia (v. Willebrand-Jürgens) at Aaland-Is. revealed the autosome-dominant inheritance of this blood disorder. Until now, it has been possible to keep watch on thrombopathia for five generations. The penetration of the thrombopathia gene is high, the expressiveness is unsteady. The bleeding tendency occurs in both sexes. On a number of patients, recent investigations have shown, that there can be a certain deficiency of factor VIII (AHG) as well as the functional disorder of thrombocytes. The role of factor VIII deficiency in the pathogenesis of thrombopathia (v. Willerand-Jürgens) is not clear yet. Recent investigations on patients with aalandish throm-bopathia have shown certain morphalogical changes in thrombocytes, not existing in thrombocytes of healthy persons.

Gli aspetti genetici del globulo rosso rappresentano oggi uno dei campi più fruttiferi in genetica ematologica, sia che essi si guardino dal punto di vista strettamente morfologico, sia da quello della loro costituzione antigene, sia per la qualità dell'emoglobina contenuta etc. Ancora limitato invece è il nostro patrimonio di conoscenze per quel che riguarda i globuli bianchi.

Eppure è un campo ricco di promesse, come il notevole numero di forme strettamente legate alla genetica sta a dimostrare. Ricordiamo ad esempio l'anomalia di Alder, quella di Pelger, l'eosinofilia familiare, la granulopenia familiare, etc. — È quindi uno dei punti fondamentali del nostro programma di lavoro uno studio sistematico degli aspetti genetici nella anatomia, fisiologia e patologia del globulo bianco. Non sto a ricordarvi i punti di notevole interesse già ottenuti e che, essendo pubblicati, vi sono già certamente noti. Vorrei invece prospettarvi alcune considerazioni di interesse prevalentemente teorico che pur interessando tutto il campo della genetica medica risaltano nella loro piena attualità nel campo delle genetica ematologica. Dovrò a questo proposito ricalcare alcuni punti già trattati nella relazione Gedda-Torrioli Riggio, ma l'analogia tra i due argomenti, fin troppo evidente, non mi permette di fare altrimenti.

1) An increase of hemoglobin A2 over 3% is regarded as one of the two fundamental manifestations of the commonest thalassemic mutant in the heterozygous condition i.e. thalassemia minima or typical microcytemia (here indicated as MA), while the other element is represented by the characteristic ensemble of the morphological and functional alterations of the erythrocytes. This assumption is based on the fact that the infrequent cases of sharp dissociation between the two elements i.e.i) red cells normality with A2 above 3 % (mA), and ii) microcytemia with normal levels of A2 (Ma). run in families and cannot be easily explained as a partial manifestation of a typical microcytemic gene.

2) The unilocal origin of the Ma variant seems to be well proved by the segregations from 5 Ma × ma (normal) matings where 10 Ma and 9 ma children have been observed. Moreover this variant has been detected among the relatives of a carrier of Hb H, born from a Ma × ma mating. This is in agreement with other recently published reports and strongly suggests that the relationship between Hb H and atypical microcytemia (with low A2) has a precise etiological significance.

3) The unilocal origin of the mA variant (normocytic thalassemia?) is at the moment less firmly established. However a family is described (mating mA × MA) where the father and one child show the same mA phenotype; moreover one other child is affected by constitutional microcytic anemia (Th. media). This finding supports the observations of Silvestroni and Bianco, who have already reported that a number of patients with intermediate thalassemic syndromes are born from mA × MA matings.

4) At the moment no data exist which enable to decide whether the different thalassemias are mutations of the same or of different loci; however if they shall be shown to be allelic, the hypothesis must be kept in mind that the Thalassemia locus is a complex locus with more than one mutation sides, responsible for different but correlated aspects of the phenotype (red cell structure and A2 level).

5) The new hemoglobin B2, is described which has been recently identified by Kunkel. Ceppellini, Dunn and Firsheim (unpublished data). Reasons are given for regarding B2 as the product of a mutation at the locus which is responsable for the synthesis of A2 (locus Hb2), The relationship of allelism between A2 and B2 is a proof of the genetic heterogeneity of the hemoglobin of the normal adult and may be taken as a model suggesting the genetic heterogeneity of hemoglobin A, notwithstanding its apparent chemical omogeneity.

6) It is concluded that the conditions generally indicated as Thalassemias represent a genetically heterogeneous group, which have nonetheless to do with related metabolic processes. It is therefore suggested that the term Thalassemia may be mantained for indicating all hereditary defects which directly interfere with hemoglobinogenesis although not producing a specific abnormal hemoglobin.

On examining all the hypotheses on thalassemia the one that seems more reliable in the onset in a paleomediterranean race.

The peoples of the Lake Chad region who form the subject of this study are inhabitants of Bornu, today an administrative province of northeast Nigeria which includes the northern Cameroons, formerly one of the great empires of interior Africa. There were several reasons why this survey of abnormal haemoglobins was undertaken. It was an obvious consideration that nothing was known of their incidence in this area; indeed for the vast complicated ethnological patchwork that comprises the peoples of northern Nigeria there have been studied to date only general samples, predominantly Hausa. It should be regarded as a matter of urgency to ascertain gene frequencies in African peoples before their differences are completely obliterated with the breakdown of tribal patterns, and before the selection pressure differentials are readjusted with the arrival of modern medicine.

Another more cogent reason however lay in the historical information available for the area. Ancient tribal traditions are supplemented by the writings of early Muslim travellers and the written documents of the people themselves, and though many of the latter records were destroyed in the several invasions of Bornu, enough remain to enable the main outline of events over the last 1,200 years to be reconstructed. The story is of a succession of invasions and immigrations by peoples of different ethnic affinities, speaking different languages, possessing different customs, ways of life and outlook; the habitat into which they came is essentially uniform, a vast plain of scrub savana. It appeared of interest to enquire whether the demands of a uniform habitat had levelled out the genetic differences expected in peoples of such diverse orieins, and if not to examine the extent to which such differences had been retained.

Die Pelger-Huet'sche Kernanomalie ist bei Aezten und Laborantinnen nahezu unbekannt. Nur zwei von etwa 350 in Westfalen systematisch befragten Krankenhaus-Aerzten waren mit diesem Begriff vertraut. Jofin (1955) berichtet aus Russland über die gleiche Unkenntnis. Seit der ersten Beschreibung der Varietät durch Pelger (1928) sind in dreißig Jahren nach Petzel und Undritz (1957) bisher 110 unabhängige Pelger-Sippen veröffentlicht worden. Das Merkmal wurde beobachtet in Bevölkerungen aller Rassen.

Die erste Schätzung der Häufigkeit in einer unausgelesenen Population hat Undritz (1939) vorgenommen. Der Untersucher rechnet mit einem Vorkommen von einer Pelger-Familie unter tausend in dieser Beziehung unauffälligen Sippen. Nachtsheim (1946-1948) hat zuerst eine größere Bevölkerung auslesefrei untersuchen können: unter etwa 20.000 Berlinern aller Altersstufen fanden sich 18 heterozygote Merkmalsträger. Die Probanden waren nicht miteinander verwandt. Nachtsheim bestätigte damit die Schätzung von Undritz. Wiedemann und Saile (1957) untersuchten 15.000 Schüler in Krefeld. Die Jungen und Mädchen waren zwischen 9 und 19 Jahre alt. In diesem auslesefreien Kollektiv sind nur 3 heterozygote Merkmalsträger gefunden worden. Die Häufigkeit beträgt also 1: 5.000. Davidson (1954) fand unter 36.000 Blutausstrichen in London 6 Fälle mit Pelger'scher Varietät. Der Untersucher gibt die Häufigkeit mit 1: 6.000 an. Leider fehlen Angaben über die Methodik der Untersuchung. Yamasowa (1953) soll nach einer Mitteilung an Undritz (cit. G. Petzel und E. Undritz, 1957) bei 20.000 Japanern nur einmal die heterozygote Manifestation beobachtet haben. Die Frequenz der Pelger-Anomalie läßt sich nur bestimmen durch größere Reihenuntersuchungen. Vergleichbar sind bisher lediglich die Ergebnisse von Nachtsheim und Wiedemann. Diese Befunde weichen stark voneinander ab.

The AA. state that favism as a disease but is not inherited the underlying biochemical rer cells defectis. The defect is present in 12,1% of the sardinian population (immigrated in Genova) and is absent in subjects of ligurian extraction. A remarkable number of sensitive subjects have no clinical disturbances at all. The inheritance is of dominant mendelian type. In the females there is a low gene penetrance and expressivity. Even if apparenty normal to the biochemical tests they frequently transmit the defect to the sons.

The possibility of a sex-linked hereditary transmission is taken into consideration.

En Sardaigne le favisme hémolytique est bien fréquent. C'est pourquoi j'ai pu conduire une étude génétique de la maladie suivant les méthodes classiques.

L'analyse d'un ensemble de 116 fréries atteintes, séparées en 3 catégories selon que les parents étaient tous les deux normaux, l'un seulement atteint ou tous les deux atteints, a donné les résultats suivants:

1. Une correspondance satisfaisante, au control par le X2, des rapports observés et prévus, suivant la méthode de Bernstein, entre les enfants atteints et les normaux, dans l'hypothèse d'une transmission héréditaire recessive de la prédisposition à la maladie, cette prédisposition étant identifiée par la maladie même, soufferte au moin une fois.

2. La disparition prèsque totale, après l'age de 30 ans, de la forte prépondérance du sexe masculin sur le féminin, observée chez les enfants atteints.

3. Une prépondérance des mâles bien plus forte parmi les enfants hospitalisés, c'est-à-dire chez les plus graves, que parmi les autres.

4. Une fréquence calculée du gène de 0.133, incompatible avec l'hypothèse d'une liaison absolue du gène au chromosome X, même en considération de la sex-ratio la plus favorable à cette hypothèse, observée chez les enfants hospitalisés (300 m % f).

5. La sex-ratio — déduite de 226 familles — entre les pères et mères atteints de 100 m % f, celle-ci aussi incompatible avec la même hypothèse.

6. Pas de différence significative entre le nombre des fréries avec un seul sexe atteint et celui des fréries avec tous les deux atteints, ce qui aurait pu indiquer une liaison incomplète au chromosome X.

The comparative studies on the changes of the skull in the familial hemolytic anemias does not support the hypotesis of Gänsslen which states that in hereditary spherocytosis oxycephaly is a consequence of precocious synostosis of the coronal suture through irritation induced by hyperplastic marrow.

On the basis of craniometric researches performed on patients and their relatives, the Authors suggest that oxycephaly might be considered as a feature referable to some peculiar racial characteristics of the populations among which the disease is manifested.

Death rates in Italy for the following groups of causes have been studied.

• Haemophilia, purpura and other haemorrhagic conditions,

• Pernicious anaemia,

• Leukhaemia and Hodgkin's disease.

A study of the historical series shows a decreasing trend in death rates for the first two groups of causes and a rapidly increasing one for the third group. The study of death rates by age and sex shows, in the three groups of causes, a high death rate under 5 and over 50 years of age, with different characteristics from one group to another. Death rates for leukhaemia are higher in males than females.

The Authors describe a pair of dizygotic twins of different sex, affected by hemolytic disease of the newborn in form of nuclear icterus. On the basis of the different severity of the disease, the Authors underline the role played not only by the immunization degree of the mother, by the type of the produced antibodies and by the placental filtration, but also by other fetal factors. Oculogyric crises and Cantelli's sign, observed up to now only in Parkinson's disease, are for the first time related to the nervous lesions induced by the icterus.

The experience of the A. on the « genetical » sex determination (according to the method of Davidson e Smith) is summarized. It is stressed that: a) « drumsticks » in the female newborns are remarkably increased - b) in monozygous twins there is a strict similarity in the number of the « drumsticks » contrary to the cases of dizygous twins.

The results obtained in cases of gonadal disgenesis are reported: of 16 patients with somatic female appearance 12 were cromatine-negative. The diagnostic importance of genetical sex determination in suspected cases of « Status Bonnevie-Ullrich » of the infants is outlined, In a reported case the diagnos's was made in the neonatal life.

The numerous protein fractions of human serum, which can be determined by immuno-electrophoretic analysis, appear one after another in the course of fetal development. By the fifth month after birth they are all present. Examining the protein fractions in monozygotic and dizygotic twins, it is possible to find the exact time of appearance of those fractions which are missing at birth, i.e. a single α2-fraction and two β2-fractions.

The appearance of these three fractions always varies from four weeks to five months after birth.

We were able to demonstrate that the synthesis of these fractions took place at the same time in monozygotic twins and at different times in dizygotic twins.

These observations confirm the hypothesis that the synthesis of proteins—either singly or in groups—may be submitted to multiple genetic influences.

Finally present concepts of the protein « serum-groups » are discussed.