A. O. Carbonara

A new restriction fragment length polymorphism in the haptoglobin gene region

SummaryDirect gene analysis of the haptoglobin gene region was carried out by Southern blotting using an Hp cDNA as probe. Two types of polymorphism were observed: one due to intragenic duplication, is characterized by a constant fragment length difference of 1700bp observed with several enzymes and by complete correspondence with the protein molecular weight polymorphism; the second type, due to point mutation, was represented by two additional restriction sites for Eco RI and Pst I, with a frequency comparable to that of other genes. These two mutations segregated together in families, suggesting that the recently described Hp related gene is closely linked to the Hp gene. Moreover, they were completely associated with each other. The evolutionary significance of this finding is discussed.

Cytogenetic findings in 4952 prenatal diagnoses. An Italian collaborative study

SummaryThe development of prenatal diagnosis in Italy was made difficult by the restrictions of the old abortion law and only in recent years has a consistent number of cases been investigated. We report the experience on prenatal chromosome diagnosis of ten Italian centers participating in a collaborative study on 4952 diagnoses performed from 1972 to 1980. The main indication groups were: advanced maternal age (2882 cases), previous child with chromosome anomaly from parents with normal karyotype (847 cases), and chromosome anomaly in one parent (97 cases). The other indications for amniocentesis, including cases without a cytogenetic risk, have been assembled into a “miscellaneous” group (1126 cases). We found 125 abnormal fetal karyotypes (2.5%) of which 89 were unbalanced (1.8%). The frequencies and types of chromosome anomalies are reported in detail for each indication group and are compared with the corresponding ones from the European Munich Conference. The great majority of these Italian data were not included in the Munich report.

Gonadal agenesis in a phenotypically normal female with positive H-Y antigen

SummaryIn a girl with primary amenorrhea, born from a consanguineous marriage, bilateral absence of gonads was established histologically. Cytogenetic studies demonstrated a 46,XY karyotype, and H-Y antigen determination was positive. In contrast with most reported cases of XY females with gonadal agenesis, normal development of female internal and external genitalia was present. Clinical and endocrinological features are reported, and the possible basis for the malformation is discussed.

True hermaphroditism with XX/XY sex chromosome mosaicism: Report of a case

A case of true hermaphroditism with 46, XX/46, XY karyotype is reported. The propositus, reared as a male, showed ambiguous external genitalia with perineoscrotal hypospadias, and internal genitalia represented by bilateral ovotestes, normal uterus and tubes. Periodic menstrual bleedings appeared at puberty. The endocrinologic data demonstrated the secretory activity of both the ovarian and the testicular tissue. The analysis of red cell, lymphocyte and serum markers, done on the propositus and on his parents, failed to show any evidence of double fertilization. On this basis, the origin of the XX/XY condition (mosaicism versus chimerism) and its developmental consequences are discussed.

Dicentric Y chromosome in a patient with gonadal dysgenesis and seminoma

SummaryA male patient with ambiguous external genitalia developed a seminoma in the left inguinal region; his internal genitalia included a streak gonad on the right and a small uterus.Cytogenetic studies demonstrated a dicentric Y chromosome with unstable behavior during cell division, which resulted in 45,X/46,X,dic(Y)/47,X,dic(Y),dic(Y) mosaicism.Immunogenetic studies allowed the identification of the male-determining H-Y antigen on both leukocytes and red cells of the patient.The significance of these results is discussed with respect to recent data on the genetic control of H-Y antigen.

A Monoclonal Antibody Detects a New Antigenic Determinant Shared by DR1 and DR4/Dw4 Molecules

A cytotoxic murine monoclonal antibody (MoAb), AC1.59, detects a new DR specificity coded by HLA haplotypes carrying DR1, DR4, DRw6, DRw8, or DRw9 alleles, thus defining a new group of cross-reacting DR specificities. Moreover, AC1.59 allows the serological definition of two genetically determined subtypes of DR4, one correlated with Dw4 and one with Dw10.

delta F508 deletion in cystic fibrosis in Italian families.

SummaryIn 20 Italian families with cystic fibrosis (CF), restriction fragment length polymorphisms were detected by five linked markers; a strong linkage disequilibrium is observed between the haplotype B (alleles 2/1 with respect to KM19/XV2c) and CF. The frequency of the ΔF508 deletion in CF chromosomes of this sample is 50%. A significant correlation is found between the absence of the ΔF508 mutation and pancreatic sufficiency.

Production and Characterization of Murine Monoclonal Antibodies against Human B Cell Surface Determinants

Abstract This paper reports the generation and characterization of murine monoclonal antibodies against monomorphic and polymorphic determinants expressed on the cell surface of human B cells.

Structural Genetic Alterations in Ig Subclass Deficiencies

Abstract Serological screening for IgG2 and/or IgG4 deficient subjects among 22.000 blood donors revealed a number of cases of isolated or multiple deficiencies, isolated IgG4 deficiency being the most common (0.245%). Southern blot analysis showed that all cases of multiple deficiency and two cases of isolated deficiency (IgG2 and IgG4) were due to deletion of the corresponding genes on both chromosomes. In IgG4-deficient subjects with no evident DNA alteration, characterization of several RFLPs within the IGHC region showed an increased frequency of certain alleles. Genotype analysis demonstrated that the variation was due to a significant increase of homozygotes for the associated alleles These data suggest that minor structural defects within the IGHC region, besides gene deletions, may be one of the prominent causes of Ig subclass deficiencies

Molecular Genetics of Haptoglobin

Abstract Southern blotting studies of the Hp and Hp related (Hpr) genes allowed to establish by RFLP linkage studies that the two genes are close to each other, as confirmed by direct molecular mapping. A nine exon structure of the rare Hp Johnson variant gene was hypothesized, supporting the proposal that it probably originated through unequal homologous crossing-over.