Mutations in a putative global transcriptional regulator cause X-linked mental retardation with α-thalassemia (ATR-X syndrome)

Gibbons, Richard J.; Picketts, David J.; Villard, Laurent; Higgs, Douglas R.

doi:10.1016/0092-8674(95)90287-2

Cited by 572 publications

(381 citation statements)

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“…53 It thought to be a nuclear protein involved in the regulation of gene expression. 42,54 In humans, a deficiency in this protein is associated with a severe mental retardation syndrome (ATR-X syndrome) which includes ␣-thalassemia, urogenital abnormalities, and a characteristic facial appearance. A role for ATRX in cancer has not yet been described.…”

Section: Discussionmentioning

confidence: 99%

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SEREX analysis for tumor antigen identification in a mouse model of adenocarcinoma

Hampton

Conry²,

Khazaeli³

et al. 2000

Cancer Gene Ther

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Evaluation of immunotherapy strategies in mouse models of carcinoma is hampered by the limited number of known murine tumor antigens (Ags). Although tumor Ags can be identified based on cytotoxic T-cell activation, this approach is not readily accomplished for many tumor types. We applied an alternative strategy based on a humoral immune response, SEREX, to the identification of tumor Ags in the murine colon adenocarcinoma cell line MC38. Immunization of syngeneic C57BL/6 mice with MC38 cells by three different methods induced a protective immune response with concomitant production of anti-MC38 antibodies. Immunoscreening of an MC38-derived expression library resulted in the identification of the endogenous ecotropic leukemia virus envelope (env) protein and the murine ATRX protein as candidate tumor Ags. Northern blot analysis demonstrated high levels of expression of the env transcript in MC38 cells and in several other murine tumor cell lines, whereas expression in normal colonic epithelium was absent. ATRX was found to be variably expressed in tumor cell lines and in normal tissue. Further analysis of the expressed env sequence indicated that it represents a nonmutated tumor Ag. Polynucleotide immunization with DNA encoding the env polypeptide resulted in strong and specific antibody responses to this self Ag in all immunized mice. Thus, SEREX offers a rapid means of identifying tumor Ags in murine cancer models. Cancer Gene Therapy (2000) 7, 446 -455

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Section: Discussionmentioning

confidence: 99%

“…This gene encodes a protein with potential DNA binding and helicase activity. 42,43 The sequence of the 2.8-kb fragment derived from MC38 mRNA was not mutated compared with the published sequence.…”

Section: Identification Of Reactive Plaquesmentioning

confidence: 99%

SEREX analysis for tumor antigen identification in a mouse model of adenocarcinoma

Hampton

Conry²,

Khazaeli³

et al. 2000

Cancer Gene Ther

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“…XH2/XNP, the gene for the ATR-X, encoding a putative DNA helicase, was recently cloned (Stayton et al, 1994;Gibbons et aL, 1995a). With single-strand conformation polymorphism analysis on cDNAs from 24 ATR-X patients, muta- Table 1.…”

Section: Discussionmentioning

confidence: 99%

“…41, No. 3, 1996 tions in nine pedigrees (7 for missense mutations, 2 for premature in-flame stop mutations) were detected (Gibbons et al, 1995a). In addition, two mutation reports, one is a splicing mutation of the gene XNP in a dysmorphic mental retardation patient without a-thalassemia (Villard et al, 1996a), and the other is a point mutation of the gene in a large family with Juberg-Marsidi syndrome (Villard et al, 1996b), were presented.…”

Section: Discussionmentioning

confidence: 99%

“…In 1991 Gibbons et al (1991) defined a new, X-linked form of mental retardation in 16 individuals with characteristic dysmorphic features and a-thalassemia (ATR-X). XH2, the gene for the disorder, mapped to Xql3, was recently identified (Gibbons et al, 1995a). To date there have been 50 published cases from 28 unrelated families in Caucasian origin and from clinical observations a well-defined phenotype has emerged (Lefort et aL, 1993;Gibbons et aL, 1995b).…”

Section: Introductionmentioning

confidence: 99%

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A japanese patient with X-linked α-thalassemia/mental retardation syndrome: An additional case report

et al. 1996

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Molecular Diagnosis and Carrier Screening for β Thalassemia

Cao

Saba²,

Galanello³

et al. 1997

JAMA

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Thalassemias are common autosomal recessive disorders especially in populations of Mediterranean, Middle Eastern, and Far Eastern descent. Relatively high incidence is also observed in people of Asian Indian origin but the incidence is more limited in those of African descent. Beta Thalassemias are heterogeneous at the molecular level, with more than 150 different molecular defects identified to date. Despite this heterogeneity, each at-risk population has its own spectrum of common mutations, usually from 5 to 10, a finding that simplifies mutation analysis. Homozygosity for beta thalassemias usually results in transfusion-dependent thalassemia major and, rarely, in mild non-transfusion-dependent conditions. Molecular diagnosis may be used to define genotypes associated with mild forms. Advances in carrier diagnosis using hematologic analysis followed by mutation analysis have made possible the population screening of women at childbearing age and prenatal diagnosis. This approach in combination with nondirective genetic counseling has resulted in a consistent decline of the birth of affected homozygotes in several Mediterranean at-risk populations, as well as knowledge of the risks of being a carrier. Molecular diagnosis of homozygotes and identification of carriers of beta thalassemia may lead to improved clinical management of patients with the disorder and prevention of the birth of affected homozygotes.

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Mutations in a putative global transcriptional regulator cause X-linked mental retardation with α-thalassemia (ATR-X syndrome)

Cited by 572 publications

References 38 publications

SEREX analysis for tumor antigen identification in a mouse model of adenocarcinoma

SEREX analysis for tumor antigen identification in a mouse model of adenocarcinoma

A japanese patient with X-linked α-thalassemia/mental retardation syndrome: An additional case report

Molecular Diagnosis and Carrier Screening for β Thalassemia

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