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Title: Deletions of Yq11 associated with short stature and the Turner syndrome. Tentative mapping of a region associated with specific Turner stigmata to proximal interval 5.

Abstract

Turner syndrome is a complex human phenotype, commonly associated with a 45,X karyotype. Mapping the Turner phenotype is difficult since hidden mosaicisms, partial monosomy and complex rearrangements are present in many affected individuals. In addition, attempts to map the genes involved to the X chromosome have failed to yield a consistent localisation. An alternative approach to map and identify Turner genes is to study XY individuals, with sex chromosome abnormalities, who present with or without characteristic Turner stigmata. We report the analysis of 4 individuals with terminal deletions of Yq. The individuals were azoospermic males without phenotypic abnormalities (2 cases) and azoospermic males presenting with a specific subset of Turner stigmata (2 cases). Breakpoints in each of the cytogenetically detectable Yq deletions were mapped by Southern analysis and Y chromosome-specific sequence tagged sites (STS). Correlation between the patients phenotypes and the extent of their deletion indicate a critical region associated with specific Turner stigmata (cubitus valgus, shield chest, short fourth metacarpals) and growth retardation at Yq at proximal interval 5. These data provide evidence that the somatic features of the Turner syndrome are most likely caused by haploinsufficiency of genes at several loci.

Authors:
; ;  [1]
  1. Immunogenetique Humaine 25 rue du Dr. Roux, Paris (France) [and others
Publication Date:
OSTI Identifier:
133718
Report Number(s):
CONF-941009-
Journal ID: AJHGAG; ISSN 0002-9297; TRN: 95:005313-0449
Resource Type:
Journal Article
Resource Relation:
Journal Name: American Journal of Human Genetics; Journal Volume: 55; Journal Issue: Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; HUMAN Y CHROMOSOME; CHROMOSOMAL ABERRATIONS; MOSAICISM; GENETIC MAPPING; PATIENTS; UROGENITAL SYSTEM DISEASES; PHENOTYPE; GENES; BIOLOGICAL MARKERS

Citation Formats

McElreavey, K., Barbaux, S., and Vilain, E.. Deletions of Yq11 associated with short stature and the Turner syndrome. Tentative mapping of a region associated with specific Turner stigmata to proximal interval 5.. United States: N. p., 1994. Web.
McElreavey, K., Barbaux, S., & Vilain, E.. Deletions of Yq11 associated with short stature and the Turner syndrome. Tentative mapping of a region associated with specific Turner stigmata to proximal interval 5.. United States.
McElreavey, K., Barbaux, S., and Vilain, E.. Thu . "Deletions of Yq11 associated with short stature and the Turner syndrome. Tentative mapping of a region associated with specific Turner stigmata to proximal interval 5.". United States. doi:.
@article{osti_133718,
title = {Deletions of Yq11 associated with short stature and the Turner syndrome. Tentative mapping of a region associated with specific Turner stigmata to proximal interval 5.},
author = {McElreavey, K. and Barbaux, S. and Vilain, E.},
abstractNote = {Turner syndrome is a complex human phenotype, commonly associated with a 45,X karyotype. Mapping the Turner phenotype is difficult since hidden mosaicisms, partial monosomy and complex rearrangements are present in many affected individuals. In addition, attempts to map the genes involved to the X chromosome have failed to yield a consistent localisation. An alternative approach to map and identify Turner genes is to study XY individuals, with sex chromosome abnormalities, who present with or without characteristic Turner stigmata. We report the analysis of 4 individuals with terminal deletions of Yq. The individuals were azoospermic males without phenotypic abnormalities (2 cases) and azoospermic males presenting with a specific subset of Turner stigmata (2 cases). Breakpoints in each of the cytogenetically detectable Yq deletions were mapped by Southern analysis and Y chromosome-specific sequence tagged sites (STS). Correlation between the patients phenotypes and the extent of their deletion indicate a critical region associated with specific Turner stigmata (cubitus valgus, shield chest, short fourth metacarpals) and growth retardation at Yq at proximal interval 5. These data provide evidence that the somatic features of the Turner syndrome are most likely caused by haploinsufficiency of genes at several loci.},
doi = {},
journal = {American Journal of Human Genetics},
number = Suppl.3,
volume = 55,
place = {United States},
year = {Thu Sep 01 00:00:00 EDT 1994},
month = {Thu Sep 01 00:00:00 EDT 1994}
}
  • A male patient with Turner-like hydrops in the newborn period (Bonnevie-Ullrich syndrome) was studied. The extensive nucchal cystic hygroma and hydrops resolved over several weeks. The karyotype was 46,X,t(Y;16)(q11.2;q24). The paternal karyotype was normal. Chromosome painting with the heterochromatic long arm repeat DYZ2 disclosed that all the hybridization was on the derivative 16. This was confirmed by chromosome painting with DYZ1, the other major Y long arm heterochromatic repeat, and DYZ3, the Y alphoid, centromeric repeat, which showed chromosomal separation of the 2 stained regions. A {open_quotes}FISHing trip{close_quotes} was performed using the Y YAC contig created in Dr. David Page`smore » laboratory. This disclosed 2 YACs located just proximal to the Y heterochromatin which {open_quotes}jumped{close_quotes} the translocation. The recent discovery of a candidate gene for the azoospermia factor (AZF) in this region suggests the possibility that there are several Y-expressed genes adjacent to the heterochromatin boundary as there are near the pseudoautosomal boundary.« less
  • The majority of Williams-Beuren syndrome (WBS) patients have been shown to have a microdeletion within 7q11.2 including the elastin gene locus. The extent of these deletions has, however, not been well characterized. Thirty-five deletion patients were tested for all polymorphic markers in the 7q11.2 region bounding ELN to define the extent of deletions associated with WBS. With only one exception, ELN, D7S1870, and one copy of the D7S489 locus (D7S489U) were always included in the deletions. One patient showed lack of maternal inheritance at D7S1870 and not at ELN or D7S489U. A product corresponding to D7S489U was amplified form YACmore » 743G6 and from the P1 clone RMC07P008, thereby localizing both to within the common deletion. The boundary of the deleted region on the proximal (centromeric) side is D7S653 and on the distal side is D7S675, neither of which were ever included in the deletion. One locus, D7S489L, was variably deleted in patients, indicating a minimum of two common breakpoints on the proximal side. At least one additional repeat amplified by D7S489 (D7S489M) was localized to a YAC contig mapping distal to the mologous to several cDNA clones in the GenBank database and contains an Alu sequence. It is possible that this and/or other repetitive sequences in this region could play a role in the mechanism of deletion. 26 refs., 5 figs., 2 tabs.« less
  • Molecular mapping techniques have defined the region of gene loss in two patients with the 5q-syndrome and uncharacteristically small 5q deletions (5q31-q33). The allelic loss of 10 genes localized to 5q23-qter (centromere-CSF2-EGR1-FGFA-GRL-ADRB2-CSF1R-SPARC-GLUH1-NKSF1-FLT4-telomere) was investigated in peripheral blood cell fractions. Gene dosage experiments demonstrated that CSF2, EGR1, NKSF1, and FLT4 were retained on the 5q-chromosome in both patients and that FGFA was retained in one patient, thus placing these genes outside the critical region. GRL, ADRB2, CSF1R, SPARC, and GLUH1 were shown to be deleted in both patients. The proximal breakpoint is localized between EGR1 and FGFA in one patient andmore » between FGFA and ADRB2 in the other, and the distal breakpoint is localized between GLUH1 and NKSF1 in both patients. Pulsed-field gel electrophoresis was used to map the 5q deletion breakpoints, and breakpoint-specific fragments were detected with FGFA in the granulocyte but not the lymphocyte fraction of one patient. This study has established the critical region of gene loss of the 5q-chromosome in the 5q-syndrome, giving the location for a putative tumor-suppressor gene in the 5.6-Mb region between FGFA and NKSF1. 54 refs., 3 figs., 2 tabs.« less
  • Turner syndrome is a complex human developmental disorder associated with the absence of the second sex chromosome (monosomy X). Cardinal features of the Turner phenotype include high intrauterine lethality, growth retardation, gonadal failure, and the variable presence of specific somatic abnormalities such as webbed neck, lymphedema, and skeletal abnormalities. Recent observations support the hypothesis that the phenotype associated with monosomy X results from haploid dosage of genes common the X and Y chromosomes that escape X-inactivation ({open_quotes}Turner genes{close_quotes}). Apart from a locus causing short stature that maps to the pseudoautosomal region on the distal short arm, the location of X-linkedmore » Turner genes is not known. Karyotype/phenotype correlations in women with partial X deletions have been inconsistent. However, previous studies have focused on sporadic sex chromosome aberrations and may have been confounded by occult mosaicism. In addition, mapping of deletions was limited by the resolution of cytogenetic techniques. I am reexamining genotype/phenotype correlations in partial X monosomy, focusing on a subset of cases in which mosaicism is highly unlikely (e.g., unbalanced X-autosome translocations, familial X deletions), and using molecular techniques to map deletions. I have collected eight cases of nonmosaic X deletions in women with varied manifestations of Turner syndrome. Cytogenetic data suggests that genes responsible for Turner anatomic abnormalities may lie within a critical region of the very proximal portion of the short arm (Xp11). Molecular characterization of the deletions is in progress. Methods include (1) fluorescence in situ hybridization of metaphase spreads from patient-derived cell lines, using cosmid probes that map to known locations on Xp, and (2) sequence tagged site (STS) content mapping of somatic cell hybrids retaining the deleted X chromosomes derived from these cell lines.« less
  • The duplication 3q syndrome is characterized by the partial trisomy of a segment of the long arm of chromosome 3. This segment, although variable in size, includes 3q26.3-q27 as the minimal region of overlap. We have previously used patient chromosome breakpoints to select cosmids within this region. In this report, we have used two- and three-color fluorescence in situ hybridization on metaphase and interphase chromosomes to perform high-resolution cytological mapping of the six cosmids identified. The results allowed us to determine the centromere-telomere orientation, the order, and the relative distances of the markers used. Because some of the markers usedmore » are part of the consensus chromosome 3 map, our data can be easily integrated with existing mapping information about this chromosome. Our data provide a framework for further physical mapping studies of this region. 11 refs., 1 fig., 2 tabs.« less