422 CORRADO BAGLIONI 



They arc, with ivw fxt'cptioii;^. which will he cDiisidcrcd separately, the 

 direct expression of mutations which aic inherited as autosomal genes. 



The first hemoi^lohin ahnormality re])orted in the literature was asso- 

 ciated with congenital methemoglobinemia (Horlein and A\'eber, 1948). 

 These authors found that the hemoglobin from patients affected by this 

 disease showed an abnormal absor])tion spectrum when in the form of 

 acid methemoglobin; the disease was transmitted as a dominant factor 

 through four generations. The first abnormal hemoglobin electropho- 

 retically different from Hb-A was found by Pauling et al. (1949) in 

 sickle-cell anemic patients. Hereditary transmission of this disease has 

 been recognized for a long time, but until Neel's investigation in 1949 it 

 was not clearly understood that the sickling gene is responsible for the 

 mild abnormality known as sickle-cell trait in heterozygotes and for 

 the severe sickle-cell anemia in homozygotes. Pauling et al. (1949) 

 reached similar conclusions independently and were able to show that 

 no Hb-A is present in homozygotes and that the heterozygotes have 

 both Hb-A and the abnormal hemoglobin (Hb-S) in the approximate 

 ratio 60:40. 



These fundamental observations stimulated several investigators to 

 examine patients affected by other forms of hereditaiy anemia and 

 normal individuals, as well, for the presence of abnormal hemoglobins. 

 Since 1950 many other abnormal hemoglobins have been discovered: 

 Hb-C by Itano and Neel (1950), Hb-D by Itano (1951), Hb-E by 

 Itano et al. (1954), and several others more recently (see Lehmann, 

 1960; Rucknagel and Neel, 1961). The enumeration of all the abnormal 

 hemoglobins reported in recent years is outside the purpose of this 

 review. Only short descrii)tions of few abnormal hemoglobins, which are 

 of particular genetic or chemical interest, will be given in this review. 

 Techniques involved in the detection of the abnormal hemoglobins have 

 been reviewed by Lehmann (1960) and by Rucknagel and Neel (1961). 

 The i^roblem of the nomenclature of abnormal hemoglobins has become 

 increasingly difficult. The letters of the al])hai)et were assigned in the 

 order of tlieir discovery to the various types of abnormal hemoglobins, 

 with the exceptions of the letters F and S, reserved to fetal and sickle- 

 cell hemoglobin. Since the abnormal hemoglobins discovered have out- 

 numbered the letters of the alpliabet, it has become necessary to name 

 the newly discovered abnormal hemoglol)ins after the place where they 

 have been found, following the example of Robinson et al. (1956). The 

 first abnormal hemoglobins discovered were variants of the normal adult 

 hemoglobin, Hb-A. Subsefjuently abnormal hemoglobins have been ob- 

 served that have been shown to be variants of Hb-F and of Hb-A:-. 

 These abnormal hemoglobins will be considered separately fi'om the 

 abnormal forms of Hb-A. 



