Biomedical subjects
Publications and source records attributed to O Zuffardi.
Two 46,XX sibs, one of female, one of male gender, and both with ambiguous external genitalia and ovotestis, were H-Y positive. The mother was H-Y negative. It is assumed that the underlying mutation was transmitted by the father, resulting in an autosomal dominant mode of inheritance. The common origin and the nature of the mutation leading to XX sex reversal are discussed.
The restriction endonuclease BSu, an isoschizomer of the enzyme HaeIII, cleaves human DNA to yield classes of fragments that are characteristic of the DNA of individuals having a Y chromosome. The fragments concerned are therefore diagnostic of the presence of Y-chromosome DNA and have been studied here with the intention of confirming the origin of various translocations thought, on other grounds, to involve the Y. The absence of the fragments from DNA of a case exhibiting absence of the fluorecent region of Yq suggests that the DNA concerned maps predominantly to Yq. Normal gender in the absence of the BSu fragments indicates that they do not function in sex determination.
An unbalanced X/Y translocation was found in a male child with malformed external genitalia and in his mother, who are respectively nullisomic and monosomic for the distal portion of Xp and have the translocated distal segment of Yq in excess. The loss of the distal portion of Xp is supposed to be the cause of the phenotypic abnormalities present in these subjects. The phenotype of our subjects is compared with those of the other cases of X/Y translocation described in the literature.
Deletion of the short arm of chromosome 9, derived from a 3:1 meiotic segregation in the mother, carrier of a balanced 9/15 translocation, was found in a 3-year-old female. Severe psychomotor retardation with delayed speech, brachicephaly, flat occiput hypertelorism and long upper lip were the main signs in the girl.
Two further cases (one previously published as D/D translocation) of 15/15 translocation in Prader-Willi syndrome are reported, which brings the total cases of this specific chromosomal anomaly in connection with this specific syndrome up to three or possibly four. It is suggested that Prader-Willi syndrome might be caused by loss of short arm material of chromosome 15.
A girl with psychomotor retardation and minor physical abnormalities, had an unbalanced X/1 translocation resulting in a partial trisomy 1q and partial monosomy for Xp. The four cases of partial trisomy for the distal segment of 1q reported in the literature showed a much more severely affected phenotype. In the present case the translocated X/1 chromosome is preferentially late replicating and there is spreading of late replication to the translocated 1q segment only in a minor proportion of the cells. The possibility of a non univocous correspondence between spreading of genetic inactivation and cytological spreading of late replication is discussed.
Prominent intensely fluorescent satellites on one chromosome 22 seem to have been transferred, during gametogenesis of a male carrier of a balanced 10/22 translocation, from the normal 22 to the translocated 22 in his daughter and son, both carriers of the translocation. Prenatal diagnosis was performed in the carrier daughter and in the chromosomally normal female foetus the satellites have jumped back to one normal chromosome 22. The phenomenon is probably due to exchanges between the short arms of chromosome 22 at meiotic pairing in the father and in his daughter. These observations give a warning for caution in the use of marker variants for paternity tests and prenatal diagnosis.
The case of a 4-month-old male with de novo partial trisomy for chromosome 14 involving the p13 leads to q24 portion is reported. He presented with growth and psychomotor retardation, peculiar facies due to nose-mouth anomalies, monolateral microphtalmia, high arched palate, and anomalies of hands and feet. These symptoms are found also in the other 8 cases of partial trisomy 14 reported in the literature. This confirms a characteristic chromosomal syndrome although the breaking points on the extra chromosome 14 are not the same in the 9 cases. The clinical picture of our case calls for careful investigations of the chronology of bone age and of the immunologic situation in further cases of total and partial trisomy 14.
A deletion of the Y chromosome at the distal portion of band q11 was found in 6 men with normal male habitus but with azoospermia. Five of them were found during a survey of 1170 subfertile males while the sixth was karyotyped because of slight bone abnormalities. These findings, together with a review of the literature, suggest that on the distal portion of the nonfluoresecent segment of the long arm of the Y, factors are located controlling spermatogenesis.
A balanced translocation t(2;12)(p25;q21) was observed in a girl with mental retardation and several somatic abnormalities. The problems of phenotype-karyotype correlations are discussed.
Partial trisomy 3q was observed in a newborn female with multiple malformations, who died in the first month of life. A balanced translocation t(3q--;15p+) was present in the mother and in other family members. The correlation between the cytogenetical and the clinical aspects is briefly discussed.