A girl with mosaicism for a dicentric X chromosome (45,X/46,X,dic(X) (Xqter→p22::p22→qter))

Summary A 12-year-old girl was examined for growth retardation and a few very discrete dysmorphologic stigmata of Turner's syndrome; the genitalia were infantile yet both ovaries possessed functioning follicles. R- and C-banding techniques and Brdu treatment demonstrated a 45,X formula in 95% of lymphocytes, with 5% presenting a 46,X,dic(X) formula. Cytogenetic and clinical problems raised by this observation are discussed in relation to data from the literature.This work was supported by grants from the Institut National de la Santé et de la Recherche Médicale (C.R.L. 75-10-42-24) and from the C.R.E.M.A.G.     

一例原发闭经46,X,psu dic(X)(p22. 3::p22.3)

国外自1974年来,已有等臂双着丝粒X的多种病例报道^[5,6]。我国1982年才开始报道,至今已报道约有6例^[1-3]。现将我室发现一例报告如下。     

G-11 staining in Turner's syndrome with mos 45,X/46,X,r(?)

Mos 45,X/46,X,r(?) in 4 patients with Turner's syndrome and no signs of virilization, and in one pair of monozygotic twins, one of them with clitoral hypertrophy, was studied using combined cytogenetic techniques and specially G-11 staining for the characterization of the X or Y origin of the rings. In all 6 patients the ring was G-11 positive, attesting its Y origin. Both twins were operated and bilateral streak gonads with a bilateral nodule of testicular tissue were found. Similar small rings were also studied in one patient with mos 46,XX/46,X,r(X) and in one nonvirilized Turner's syndrome patient with a larger ring; in these two cases the ring was G-11 negative. It seems that the small rings occasionally found in Turner's syndrome are more frequently from Y origin and therefore prophylactic gonadectomy should be considered.     

Analysis of the DNA replication pattern of a translocation (tX/X,qter→p221::p223→qter) chromosome in leukocyte and fibroblast cultures

Summary The results of a detailed analysis of DNA replication in a late replicating tX/X chromosome (qter p221::p223 » qter) are reported. The chronology of DNA replication has been analyzed by comparing (a) the replication patterns of each of the two moieties of the translocation chromosome in different cells and (b) the two moieties with each other in the same cell. The study has been done on leukocyte and fibroblast cultures after BUdR incorporation. A comparison with the late replication pattern of the normal X chromosome has also been done.     

Bisatellited dicentric chromosome: A report on a case with karyotype 47,XY,+psu dic(22)t(22;22)(22pter→cen→22q11::22q11→22pter)

Summary A 12-year-old boy with mental retardation and congenital anomalies was found to have a supernumerary small marker chromosome. This marker chromosome was proved to be bisatellited and dicentric by G-, C-, R-banding and the silverstaining technique.     

45,X/46,XY qh? Karyotype and Aspermia. A case report

A 41-years old male with short stature, abnormal male sex differentiation, aspermia and schizoid character disorder is described. The patient was studied from clinical, endocrinological and genetic perspectives. Cytogenetical analysis revealed a chromosomic mosaicism formed by two normal lines 45X and 46,XY qh^?. Molecular studies on AZF region evidenced that it was conserved. The correlation of the symptoms with the cytogenetic finding is discussed.     

A point mutation,R59G,within the HMG-SRY box in a female 45,X/46,X,psu dic(Y)(pter→q11::q11→pter)

We report a molecular and cytogenetic investigation of a psu dic(Yp) chromosome identified in blood and ovarian tissue from a female with mosaic karyotype 45,X/46,X,+ psu dic(Yp). FISH analysis showed that the psu dic(Yp) has two copies of the short arm, two centromeres and two copies of the proximal long arm. PCR analysis also confirmed the presence of the SRY gene and the Y centromere, and also confirmed the deletion of the Y-heterochromatic region. Because of the possibility of a mutation, a fragment of 609 bp of the SRY gene was sequenced from independent PCR products. The analysis of the sequence indicated the presence of two different copies of the gene: one presented a point mutation, R59G, within the HMG-box; the other had a sequence identical to that already published. Both sequences were found at a proportion of 1:1. The absence of a 46,XY cell line suggests that the rearrangement took place during gametogenesis or during the first division after fertilization. Also, the existence of different sequences of the SRYgene in the same Y chromosome suggests that the formation of the dicentric took place prior to the mutation of the SRY gene. To our knowledge, this is the first time that a mutation has been described in codon 59 within the HMG- SRY box, and also the first case of a psu dic(Yp) chromosome that displays two different copies of the SRY gene.     

An XX male with a 46,XX/47,XX,+Y(q12→qter) karyotype

Summary We describe a male with the karyotype 46,XX/47, XX,+Y(q12qter), which may be interpreted as due to an insertion (Y;X)(Yq11Yq12;Xp22) or to mosaicism, 46,XX/47, XX,+Y(12qter). In any case, some of the H-Y determining genes may be located on the long arm of the Y chromosome.     

Duplication of the segment q12.2→qter of chromosome 22 due to paternal inversion 22(p13q12.2)

Summary A 1730-g male infant, born at 37 weeks gestation, had multiple congenital anomalies, consisting of microcephaly, hypertelorism, bilateral cleft lip and palate, micrognathia, lowset ears, and cryptorchidism. Chromosome analysis showed a recombinant 22 derived from the paternal inversion (22) (p13q12.2). The proband's karyotype is 46,XY,rec(22),dup q,inv(22)(p13q12.2)pat, which has a duplication of q12.2qter. An identical recombinant has been reported in a female infant in Mexico whose mother was a carrier of the inversion. Similar congenital anomalies present in these two patients demonstrate the phenotype of duplication of the distal long arm 22. This report also documents the occurrence of an identical inversion in two apparently unrelated Mexican families.     

Interstitial deletion of the long arm of chromosome 7 46,XX,del(7)(pter→q2200::q3200→qter)

Summary We present a boy with the karyotype 46,XY,r3 and a phenotype with psychomotor and growth retardation, craniofacial anomalies, syndactyly of the toes, and edema of the feet. The karyotypes and phenotypes of both parents are normal.     

A boy with 47,X,del(X)(p11→q13::q21→q24),del(Y)(q11)

Summary A patient is described carrying a duplication 4p12pter due to a paternal translocation: 46,XY,t(4;16) (p12;p13). Involvement of chromosome No. 16 and the heterogeneity of the clinical picture in cases with dup (4p) are discussed.Postdoctoral fellow of the Deutsche Forschungsgemeinschaft.     

A case of hyperlipidemia with homozygous apolipoprotein E5 (Glu3→Lys)

In this study, we present clinical feature of a novel case with homozygous apolipoprotein (apo) E5.The patient was a 53-year-old Japanese woman. She was from a small island off the coast of Kagoshima Prefecture, Japan. Her parents were first degree cousins. No corneal opacification, xanthomatosis, lymphadenopathy, or hepatosplenomegaly was observed. There have been no signs of clinically overt atherosclerosis to date. Her serum total cholesterol, triglycerides (TG) and high-density lipoprotein (HDL)-cholesterol levels were 11.6, 6.1 and 1.2 mmol/l, respectively, and apo A-I, A-II, B, C-II, C-III and E levels were 121, 34.8, 269, 10.4, 25.7 and 10.3 mg/dl, respectively. Serum lipoprotein profile analyzed by agarose gel electrophoresis and differential staining revealed markedly increased cholesterol and TG in both β and preβ-migrated lipoproteins, whereas α-migrated lipoprotein showed decreased cholesterol. Her apo E isoform analyzed by isoelectric focusing (IEF) was found to be homozygous apo E5.Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis of her apo E and lipoprotein lipase (LPL) genes revealed that she had a homozygous apo E (Glu³→Lys) and heterozygous LPL variant Ser⁴⁴⁷ to Ter. Her son and daughter, both of whom had hyperlipidemia, were found to have apo E3/5 phenotype. Direct sequencing analysis of her apo E gene confirmed a homozygous one nucleotide change: G to A at nucleotide position of 2836 in the exon 3, resulting in Glu³→Lys mutation.This is the first report of lipids and lipoprotein profiles in patients with homozygous apo E5 (Glu³→Lys).     

45,X/46,X,idic(X)/47,X,idic(X),idic(X)嵌合体核型的研究

最常见的人类X染色体的结构异常是长臂等臂X染色体,以及X染色体与常染色体之间的易位。关于idic(X)染色体结构异常的病例较为罕见。国外Chapella等曾有研究,国内周氏等首次报道了有关idic(X)染色体结构异常的病例。     

Partial duplication of the short arm of chromosome 9 (p13→p22) in a child with typical 9p trisomy phenotype

Summary A 3-year-old girl with duplication 9 (p22p13) is reported. The presence of a classical 9p trisomy phenotype in this patient suggests that this region (or part of it) is responsible for the major, typical clinical stigmata of this partial autosomal trisomy syndrome.     

Women heterozygous for deficiency of the (p21 → pter) region of the X chromosome are fertile

Summary A woman balanced carrier of a X/15 translocation gave birth to a balanced infertile son and three unbalanced Xp- fertile daughters. This family and the other eleven cases of Xp- fertile women found in the literature demonstrate that loss of the p21 pter region of the X chromosome is compatible with fertility, probably because it leaves on Xp the region which is never inactivated.     

A case of an intersex horse with 63,X/64,XX/65,XX,del(Y)(q?) karyotype

Cytogenetic and molecular genetic studies of an intersex horse have been carried out. The investigated animal had overall male body conformation; however, its external genitalia consisted of incompletely developed vulva and penis. The X and Y chromosome painting probes detected three cell lines in the examined horse: 63,X, 64,XX and 65,XX with a fragment of a Y chromosome (del Y). The DNA analysis with the PCR and PCR/RFLP methods showed absence of SRY,AMELY and ZFY genes as well as of six Y microsatellite markers (YM2, YP9, YJ10, YE1, YH12, and YA16). These results suggest that the Y chromosome fragment detected in the investigated animal was the result of a deletion of a euchromatic fragment comprising the above-mentioned markers.     

A newborn child with karyotype 47,XX,+der(12) (12pter→12q12::8q24→8qter),t(8;12) (q24;q12) pat

Summary A case of Meckel or Gruber syndrome is reported, together with a survey of the relevant literature of recent years (1971–1977), in reference to a probably autosomal recessive inheritance of this malformation.     

Charcot-Marie-Tooth disease 1A (CMT1A) associated with a maternal duplication of chromosome 17p11.2→12

We report here the second case of Charcot-Marie-Tooth disease 1A (CMT1A) with a cytogenetically visible de novo direct duplication of 17p11.117p12. A male child who was initially referred for developmental delay and dysmorphism was subsequently shown to have significantly reduced motor nerve conduction velocities characteristic of CMT1A. This patient was not informative for the DNA markers mapping to the CMT1A region; however, with DNA markers pA10–41 and EW503 that map proximally and distally with respect to the disease locus, a dosage difference was observed between the two alleles. Comparison with parental genotypes indicated a de novo maternal duplication. Pulsed field gel analysis using probe VAW409R3a indicated that a 500-kb SacII junction fragment usually associated with CMT1A was absent in this patient. These findings confirm that the disease phenotype is probably caused by a gene dosage effect.     

A case of systemic lupus erythematosus (SLE) and Sj?gren's syndrome associated with anti-T3 autoantibodies

A case of systemic lupus erythematosus (SLE) associated with Sj?gren's syndrome had extremely low serum triiodothyronine (T3) with normal levels of serum thyroxine (T4) measured by single antibody radioimmunoassays (RIAs) and thyroid stimulating hormone (TSH) during steroid treatment. Measurement of serum T3 and T4 with double antibody RIAs showed unusually high T3 and normal T4 concentrations. Examination of her serum revealed the presence of IgG class anti-T3 autoantibodies whose Scatchard plot was analyzed in two components; one with a higher associate constant (8.6 X 10(8)M-1) and a lower binding capacity (5.6 X 10(-7) mol/ml serum); the other a lower associate constant (3.5 X 10(7)M-1) and a higher binding capacity (2.1 X 10(-6) mol/ml serum). Antithyroglobulin (Tg) autoantibody has been positive throughout the seven year observation period. A significant positive correlation between titers of anti-Tg autoantibodies indicated that the antigen of anti-T3 antibodies in the patient could be T3 containing antigenic site(s) on the Tg molecule.     

Gene dosage evidence for the regional assignment of GPT (glutamate-pyruvate transaminase; E. C. 2.6.1.2) locus to 8q24.2→8qter

Summary The results of a study on the expression of GPT (glutamate-pyruvate transaminase; E. C. 2.6.1.2) in a child with a partial trisomy of chromosomes 8 and 14 are presented. A gene dosage effect supporting the regional assignment of the GPT locus to 8q24.28qter is demonstrated.