Trisomy 9p with an isochromosome of 9p

An 18 1/2-year-old female is described with moderately severe mental retardation, the phenotype of the trisomy 9p syndromy, and an isochromosome for the short arm of a chromosome 9, contained in an unique karyotype, 46,XX,-9,t(7q9q),+ iso 9p.     

Trisomy 9p with i(9p) and t(9q18p)

Summary The trisomy 9p syndrome in a 2-year-old girl with moderate mental retardation is presented. She has a unique karyotype with a de novo isochromosome 9p and a translocation between 9q and 18p.     

Trisomy 9p resulting from maternal 9/21 translocation

Summary The clinical picture found in a child with trisomy 9p confirmed that this chromosomal syndrome is a entity, which arises from maternal translocation t(9;21).     

The dermatoglyphic and clinical features of the 9p trisomy and partial 9p monosomy syndromes

Summary The physical and dermatoglyphic features obtained from published reports of 128 patients with the trisomy 9p syndrome and 27 patients with the partial 9p monosomy syndrome are tabulated. This information is also provided on two new individuals with each of these chromosomal disorders. The dermal ridge patterns and palmar creases of trisomy 9p which are most helpful from a diagnostic standpoint are zygodactylous or absent palmar digital triradii, brachymesophalangy, reduced total finger ridge count, complex thenar/ID I patterns, transverse palmar ridge alignment, simian creases, distal axial triradii, and great toe and hallucal arch patterns. The characteristic features in partial 9p monosomy include dolichomesophalangy with accessory finger flexion creases, digital whorl patterns and elevated total finger ridge count, distal axial triradii, simian creases, and palmar dermal ridge dissociation.     

Genetics of the +p9 syndrome

Summary Four 46,XY siblings with congenital bilateral megalorchidia, macrogenitosomia, and severe mental deficiency were investigated. The testicular size was significantly larger than age-matched normal males. A normal hypothalamic-pituitary gonadotropin function was demonstrated by the finding of normal levels of luteinizing and follicle-stimulating hormones in blood samples drawn at frequent intervals and by normal responses to gonadotropin-releasing hormone and testosterone adminstration. A normal testicular function was shown by the finding of normal (a) plasma testosterone and estradiol levels, (b) gonadal response to human chorionic gonadotropin, (c) sperm analysis, and (d) morphology and cell architecture of the testes. Adrenal function was found to be within normal limits. These results demonstrated the existence of normofunctional testicular hyperplasia. The family studies suggested that this distinct congenital disorder is inherited as an X-linked recessive trait.Presented at the annual meeting of the American Society of Human Genetics, Baltimore, Md., October 8–11, 1975. Abstract published in: Amer. J. hum. Genet., 27/6, 23A (1975).     

Phenotypic and cytogenetic spectrum of 9p trisomy

Trisomy 9p is one of the most frequent autosomal anomalies compatible with long survival rate. The spectrum of clinical severity in trisomy 9 roughly correlates with the extent of trisomic chromosome material. Trisomy 9p is a clinically well delineated syndrome and of all stigmata craniofacial dysmorphism is most specific. In this study we report five cases with de novo trisomy 9p. The study aimed at the identification of the genotype/phenotype correlations in patients with different breakpoints. GTG banding, DAPI stain, whole chromosome paint, centromere, telomere and 9p21 specific locus probes demonstrated that partial trisomy 9p in case 1 was due to isochromosome 9p with translocation of the long arm of re-arranged chromosome 9 onto the short arm of chromosome 13, cases 2 and 3 had intrachromosomal duplication of the short arm of chromosome 9 [dup(9)(p21p24)], case 4 had "classical" 9p trisomy and case 5 had duplication of whole short arm and part of the long arm of chromosome 9 (partial 9 trisomy). Although cases 1 to 4 had trisomy involving 9p, cases 1 and 2 exhibited the classical clinical manifestations of 9p trisomy, while cases 3 and 4 had additional features overlapping with Coffin-Siris syndrome. The present study strengthens the association of Coffin-Siris syndrome and 9p, the significance of such observations may point to possible gene location of Coffin-Siris syndrome on 9p. Case 5 had additional manifestations more than those typical of trisomy 9p which could be due to duplication of 9q21 region. Wide gap between 1st and 2nd toes, observed in the studied cases, can be added to the phenotype of this trisomy. Three of our cases had brain malformations, case 3 had dilated ventricles with hypogenesis of corpus callosum, case 4 had agenesis of corpus callosum, and case 5 had Dandy-Walker malformation. We also suggest that dosage effects of genes located in 9pter-q22 contribute to the etiology of Dandy-Walker syndrome. We recommend MRI studies as a routine in all cases with trisomy 9p.     

Trisomy 9q-. a variant of the 9p trisomy syndrome.

A low-birth-weight near-term male infant was found to have a non-familial 47,XY chromosome complement with an extra medium-sized metacentric chromosome slightly larger than a number 16. By Giemsa-trypsin (G-banding) this extra chromosome was determined to be a number 9 with deletion of approximately half of the long arm at region q 22. Chromosome studies on the clinically normal 38-year-old mother showed a balanced translocation with the deleted portion attached onto the distal end of a number 8 short arm, i.e. 46,XX,t(8;9)(p23;q22). Nondisjunction during meiosis of this woman's normal and deleted number 9 chromosomes is the basis of the child's abnormalities. One half-sibling of the child has a balanced translocation similar to that in the mother. Chromosome analyses on 4 others of the child's maternal half-siblings and on the maternal grandmother all showed normal patterns.     

Interaction between the cell-cycle-control proteins p34cdc2 and p9CKShs2. Evidence for two cooperative binding domains in p9CKShs2.

A universal intracellular factor, the 'M-phase-promoting factor' (MPF), displaying histone H1 kinase activity and constituted of at least two subunits, p34cdc2 and cyclin Bcdc13, triggers the G2----M transition of the cell cycle in all organisms. The yeast p13suc1 and p18CKS1 subunits and their functionally interchangeable human homologues, p9CKShs1 and p9CKShs2, directly interact with p34cdc2 and may actually be part of the MPF complex. We have chemically synthesized p9CKShs2 and several of its peptide domains in order to investigate the binding of p9CKShs2 and p34cdc2. Several arguments support the hypothesis that the N-terminal half (peptide B) and the C-terminal half (peptide E) each contain a p34cdc2-binding site and that these two binding domains cooperate in establishing a stable p9CKShs2-p34cdc2 complex: (a) only the combination of peptides B + E, and not B or E alone, is able to elute the cdc2 kinase from p9CKShs1-Sepharose beads; (b) only immobilized peptides B + E, and not immobilized B or E, bind the cdc2 kinase; (c) only the peptides B + E combination, and not B or E alone, can compete with p9CKShs1 for cdc2 kinase binding; (d) only when supplemented with E or B free peptide does the cdc2 kinase bind to B- or E-Sepharose beads, respectively. No binding occurs in the absence of free peptide. This additivity cannot be attributed to the formation of a B-E complex mimicking the full-length p9CKShs2. The cyclin B subunit is not required for the formation of the p9CKShs2-p34cdc2 complex through these two binding domains. The implications of the existence of two cooperative p34cdc2-binding domains in p9CKShs2 on the structure of the active M-phase-specific kinase is discussed.     

p53: Guardian of reprogramming

The reprogramming of somatic cells to induced pluripotent stem (iPS) cells is one of the major discoveries of recent years. The development and application of patient specific iPS lines could potentially revolutionize cell-based therapy, facilitating the treatment of a wide range of diseases. Despite the numerous technological advancements in the field, an in-depth mechanistical understanding of the pathways involved in reprogramming is still lacking. Several groups have recently provided a mechanistical insight into the role of the p53 tumor suppressor pathway in reprogramming. The repercussions of these findings are profound and reveal an unexpected role of p53 as a "guardian of reprogramming", ensuring genomic integrity during reprogramming at the cost of a reduced efficiency of the process. Here we analyze the latest findings in the field and discuss their relevance for future applications of iPS cell technology.     

Ambiguous genitalia by 9p deletion inherent to a dic(Y;9)(q12;p24)

We describe here a 3-month-old male infant with brachy-plagyocephaly, short neck, widely spaced nipples, mild hypertonia, and ambiguous external genitalia but with both testes in the scrotum and no Müllerian derivates. His karyotype was 45,X,der(Y;9)(q12;p24).ish der(Y;9)(DYZ3+,SRY+,9ptel-) de novo. This patient's impaired sex differentiation is consistent with gonadal dysgenesis and compares with the male-to-female sex reversal secondary to a partial 9p deletion in spite of an intact Yp or SRY locus documented in 24 patients including a sex-reversed girl with a (Y;9) dicentric derivative. As for the cytogenetic findings, this case represents the second instance of a de novo pseudodicentric (Y;9) chromosome with loss of both distal 9p and Yq12 regions, apparent intactness of SRY, and consistent or preferential inactivation of the Y centromere. In addition, the possible 9p23p-p22 duplication observed in this case evokes the concomitant 9p22-p21 duplication documented in the previous girl with a (Y;9) derivative. Hence, these striking similarities point to a nonrandom Y;9 rearrangement in patients with either sex reversal or gonadal dysgenesis. Even if the present pseudodicentric derivative had inactivated the Y centromere, the existence of some variant cells points to functional dicentricity as it has been documented in other Y;autosome dicentric derivatives.     

Double autosomal chromosomal aberration (3p trisomy/9p monosomy) and sex-reversal

A 26-year-old girl with multiple congenital malformations, sex-reversal, and partial trisomy 3p/monosomy 9p is described. A possible influence of autosome aberrations on sexual differentiation is discussed.     

Nuclear-accumulation kinetics of p9 CksHs1 and p9 CksHs2 in live plant cells correlate with immunochemical characteristics

Summary The two human homologues of the fission yeast cell cycle protein p13 ^suc1 displayed structural characteristics consistent with their existing in solution as differently folded monomers despite 81% identity with respect to their primary structures and both being capable of fulfilling the functions of their homologues in fission and budding yeasts. Carboxyfluorescein-labelled p9 ^CksHs1 and p9 ^CksHs2 retained their native structures. When microinjected into live stamen hair cells ofTradescantia virginiana, the labelled proteins accumulated in the nuclei of the cells. Markedly different nuclearaccumulation kinetics indicated that the human proteins interact differently with other cellular constituents, which supports the proposition that they may have different roles in cellular regulation.Abbreviations Cdk cyclin-dependent kinase - tris tris(hydroxymethyl)aminomethane - Hepes N-(2-hydroxyethyl)piperazine-N-(3-ethanesulphonic acid) - CF 5(6)-carboxyfluorescein-N-hydroxysuccinamide ester - SDS-PAGE sodium dodecyl sulphatepolyacrylamide gel electrophoresis - IEF isoelectric focusing - DEAE Sephacel diethylaminoethyl Sephacel - ELISA enzyme-linked immunosorbent assay - IgG immunoglobulin     

Asymmetrically localized Bud8p and Bud9p proteins control yeast cell polarity and development

Diploid strains of the budding yeast Saccharomyces cerevisiae change the pattern of cell division from bipolar to unipolar when switching growth from the unicellular yeast form (YF) to filamentous, pseudohyphal (PH) cells in response to nitrogen starvation. The functions of two transmembrane proteins, Bud8p and Bud9p, in regulating YF and PH cell polarity were investigated. Bud8p is highly concentrated at the distal pole of both YF and PH cells, where it directs initiation of cell division. Asymmetric localization of Bud8p is independent of the Rsr1p/Bud1p GTPase. rsr1/bud1 mutations are epistatic to bud8 mutations, placing Rsr1p/Bud1p downstream of Bud8p. In YF cells, Bud9p is also localized at the distal pole, yet deletion of BUD9 favours distal bud initiation. In PH cells, nutritional starvation for nitrogen efficiently prevents distal localization of Bud9p. Because Bud8p and Bud9p proteins associate in vivo, we propose Bud8p as a landmark for bud initiation at the distal cell pole, where Bud9p acts as inhibitor. In response to nitrogen starvation, asymmetric localization of Bud9p is averted, favouring Bud8p-mediated cell division at the distal pole.     

Gene dosage effect for GALT in 9p trisomy and in 9p tetrasomy with an improved technique for GALT determination

Summary A new born male and a three-year-old female with various dysmorphic features were both found to have a supernumerary chromosome. Clinical and cytogenetic findings confirmed the existence of a pure de novo 9p tetrasomy in the first case and a pure de novo 9p trisomy in the second case. Gene dosage effects were demonstrated for galactose-1-phosphate uridyltransferase GALT (EC 2.7.7.12) using an improved method for the assay of this enzyme in red blood cells. These findings are in agreement with previous results on similar cases and therefore confirm the assignment of the locus for GALT to 9p.