PMX2B,a new candidate gene for Hirschsprung's disease

Hirschsprung's (HSCR) disease is a congenital intestinal malformation of the enteric nervous system. It is a multigenic malformation and until now, eight genes have been involved in the etiology of this disease: genes encoding proteins of the RET signaling pathway (RET, GDNF and NTN), genes participating in the endothelin (EDN) type B receptor pathway (EDNRB, EDN3 and ECE-1), the SOX10 gene and the SIP1 gene that is mutated in syndromic forms of HSCR. Mutations of these genes are found in not more than 50-60% of affected individuals. Here, we report on the results of a molecular cytogenetic study performed in a girl who presented with a syndromic short segment HSCR associated with a de novo t(4;8)(p13;p22) translocation. A comparative genomic hybridization (CGH) study found a 4p12p13 deletion. A molecular characterization of this rearrangement showed that the 4p13 deletion was 5 Mb in length and included the paired mesoderm homeobox gene (PMX2B) (MIM 603851), a gene expressed in the human embryonic gut and essential for the development of autonomic neural crest derivatives. The present observation suggests that PMX2B haploinsuffciency might predispose to HSCR.     

Meiotic behaviour of a new complex X-Y-autosome translocation and amplified heterochromatin in Jumnos ruckeri (Saunders) (Coleoptera, Scarabaeidae, Cetoniinae)

Species belonging to the Cetoniinae subfamily studied so far possess 20 chromosomes, including a small X and a punctiform Y: 20,Xyp in the males. In a series of species from the Goliathini tribe under study we found a very unusual karyotype, with 12 autosomes and large sex chromosomes (14,neoXY) in Jumnos ruckieri from Thailand. Applying various techniques including pachytene bivalent spreading, we showed that 40% (mitotic and meiotic prophases) to 60% (metaphases) of the karyotype length was composed of heterochromatin. Both sex chromosomes were NOR carriers. At pachynema they underwent a complete synapsis of their distal regions, indicating their autosomal origin. At contrast, their very uneven central regions remained separated, but associated with nucleolus material. This association persisted until diakinesis, forming a pseudo-chiasma between the neoX and the neoY, which were always in end-to-end association. Compared to free autosomes the autosomal parts of the neo-sex chromosomes had a significant lack of interstitial chiasmata, indicating a possible lack of recombination at their proximal regions. As in the cases of X-autosome translocations in mammals, autosomal and gonosomal parts of the neo-sex chromosomes were insulated by heterochromatin, which may be a necessary condition to avoid deleterious position effects, whatever the mechanisms of gene dosage compensation.     

Cytogenetic evidence that the Saethre-Chotzen gene maps to 7p21.2

Evidence for the location of the Saethre-Chotzen acrocephalosyndactyly mutation on 7p21–22 is based on genetic linkage studies in families segregating for this autosomal dominant disorder. Linkage studies were guided by several reports of chromosome deletions in this region giving rise to craniosynostosis and some other manifestations of Saethre-Chotzen syndrome. We report on a family where a father and daughter carry an apparently balanced t(7;10)(p21.2;q21.2) translocation (de novo in the father) and have the Saethre-Chotzen syndrome. These observations support the localization of the Saethre-Chotzen gene to 7p21.2. © 1993 Wiley-Liss, Inc.     

Cell lines that support replication of a novel herpes simplex virus 1 UL31 deletion mutant can properly target UL34 protein to the nuclear rim in the absence of UL31

Previous results indicated that the herpes simplex virus 1 (HSV-1) U(L)31 gene is necessary and sufficient for localization of the U(L)34 protein exclusively to the nuclear membrane of infected Hep2 cells. In the current studies, a bacterial artificial chromosome containing the entire HSV-1 strain F genome was used to construct a recombinant viral genome in which a gene encoding kanamycin resistance was inserted in place of 262 codons of the 306 codon U(L)31 open reading frame. The deletion virus produced virus titers approximately 10- to 50-fold lower in rabbit skin cells, more than 2000-fold lower in Vero cells, and more than 1500-fold lower in CV1 cells, compared to a virus bearing a restored U(L)31 gene. The replication of the U(L)31 deletion virus was restored on U(L)31-complementing cell lines derived either from rabbit skin cells or CV1 cells. Confocal microscopy indicated that the majority of U(L)34 protein localized aberrantly in the cytoplasm and nucleoplasm of Vero cells and CV1 cells, whereas U(L)34 protein localized at the nuclear membrane in rabbit skin cells, and U(L)31 complementing CV1 cells infected with the U(L)31 deletion virus. We conclude that rabbit skin cells encode a function that allows proper localization of U(L)34 protein to the nuclear membrane. We speculate that this function partially complements that of U(L)31 and may explain why U(L)31 is less critical for replication in rabbit skin cells as opposed to Vero and CV1 cells.     

Sperm analysis by FISH in a case of t(17; 22) (q11; q12) balanced translocation: case report

Individual sperm from men with balanced translocations have different chromosomal contents. Thus, an estimation of the overall sperm chromosomal imbalance of such patients could help to give the couple an adapted genetic counselling. We report here the study of a balanced translocation carrier, t(17;22) (q11;q12) whose reproductive history reported four miscarriages. Moreover, he had an abnormal semen analysis with oligoteratozoospermia. The meiotic segregation pattern was examined in 700 sperm, using fluorescence in-situ hybridization (FISH). Nineteen percent of the sperm had balanced translocations or were normal. All other sperm were unbalanced (81%) and their distribution was observed as follows: the frequencies of adjacent 1, adjacent 2 and 3:1 segregations were 12.9, 5.8 and 46.8% respectively. Among the segregations scored, 13.7% were related to second meiotic division abnormalities. Less than 2% of the total sperm scored were not explained. The 3:1 segregation was present at a very high rate, which is very unusual. In cases of balanced translocations, we believe that no general features can be drawn. Thus, the FISH technique may be very helpful for genetic counselling, which remains an important step and must be done with care.     

Characterization of the translocated chromosome using fluorescencein situ hybridization and random amplified polymorphic DNA on twoTriticum aestivum—Thinopyrum intermedium translocation lines resistant to wheat streak mosaic or barley yellow dwarf virus

Fluorescencein situ hybridization (FISH) was used to determine the breakpoint of the translocation chromosome in two bread wheat (Triticum aestivum) germplasm lines withThinopyrum intermedium chromatin carrying resistance to either wheat streak mosaic virus (WSMV) or barley yellow dwarf virus (BYDV). In addition, genome-specific random amplified polymorphic DNA (RAPD) markers were used to ascertain the genomic sources of theTh. intermedium chromosomes carrying the WSMV or BYDV resistance. CI17766, a WSMV-resistant wheat germplasm line derived from induced homoeologous pairing by using theph1b mutant, had a translocation chromosome composed of the complete 4AL and about 45% of proximal 4AS from wheat, and the entire 4ES ofTh. intermedium. The BYDV-resistant translocation line, TC14, derived from tissue culture, had a very short distal segment of 7StL fromTh. intermedium terminally attached to 56% of the proximal 7DL. These observations indicate that translocations in these wheat germplasm lines did not involve centromeric breaks and fusion but were a result of homoeologous chromosome recombination.accepted for publication by J. S. (Pat) Heslop-Harrison     

A de novo translocation, 14q21q,with a microchromosome—14p21p

A familial translocation, t(14;21)(14p21p;14q21q), in a mother and her child is described. The translocation was ascertained through the birth of a Down syndrome baby with the chromosome constitution 47,XX,-14, +der 14, +der 21,t(14;21)(q11; p12) mat. A 1:3 segregation in the maternal meiosis is suggested for the evolution of the unbalanced chromosome state. The main translocated chromosome 14q21q mimics the product of a Robertsonian translocation, while the 14p21p chromosome has the morphology of a satellited microchromosome. The cytogenetic nature of this translocation is discussed.     

Familial insertional translocation of a portion of 3q into 11q resulting in duplication and deletion of region 3q22.1→q24 in different offspring

The use of elongated prophase and prometaphase chromosome preparations has allowed detection of an insertion of a small segment of 3q into 11q in a kindred with 4 balanced carriers and 8 unbalanced offspring. Those with partial 3q deletion have a true multiple congenital anomalies/mental retardation (MCA/MR) syndrome with an appearance suggestive of the Schwartz-Jampel syndrome.