Mutations in a new gene, encoding a zinc-finger protein, cause tricho-rhino-phalangeal syndrome type I

Momeni, Parastoo; Glöckner, Gernot; Schmidt, Olaf; Holtum, D. von; Albrecht, Beate; Gillessen‐Kaesbach, Gabriele; Hennekam, Raoul C. M.; Meinecke, Peter; Zabel, Bernhard; Rosenthal, André; Horsthemke, Bernhard; Lüdecke, Hermann Josef

doi:10.1038/71717

Cited by 295 publications

(342 citation statements)

References 17 publications

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“…22 The characteristics of the present patient, including multiple exostoses, mental retardation, short stature, small head, unusual facial appearance, and cone-shaped epiphyses of the hands, sufficiently fulfilled all the major criteria of this disease, 14,19,20 except for a bulbous nose. Recently, patients with clinical features very similar to LGS, but with epilepsy, were reported by two authors 23,24 as a different criteria from LGS.…”

Section: Discussionsupporting

confidence: 52%

Tetraparesis due to exostotic osteochondroma at upper cervical cord in a patient with multiple exostoses–mental retardation syndrome (Langer–Giedion syndrome)

et al. 2004

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Study design: Case report of a severe upper cervical cord compression and tetraparesis by a massive cervical exostotic osteochondroma in a patient with multiple exostoses-mental retardation syndrome (Langer-Giedion syndrome; LGS). Objective: To describe this very rare pathological condition and the results of surgical intervention. Setting: Gifu, Japan. Methods: A 23-year-old man was referred to our clinic because of progressing tetraparesis. He had previously been diagnosed with hereditary multiple exostoses and mental retardation. As he had not complained of any symptoms, his family only noticed the tetraparesis after advanced deterioration. His face possessed the pathognomic features of LGS. A postmyelogram CT scan demonstrated an exostotic mass arising from the left-side C2 pedicle with associated severe spinal cord compression. He was diagnosed with LGS. Hemilaminectomy on the left side and resection of the osteochondroma were performed. Results: At 5 years postoperatively, a neurological examination showed the full return of all motor functions. The CT scan revealed no intracanalar recurrence of the tumor. Conclusion: In this case of severe tetraparesis due to cervical osteochondroma, decompression by hemilaminectomy provided excellent results. In patients with LGS and intracanalar osteochondroma, the neurological deficit may be masked by mental retardation. Hence, awareness of this pathological condition will help clinicians diagnose it at an early stage.

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Section: Discussionsupporting

confidence: 52%

Tetraparesis due to exostotic osteochondroma at upper cervical cord in a patient with multiple exostoses–mental retardation syndrome (Langer–Giedion syndrome)

et al. 2004

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“…Proper concentrations were determined and samples were sequenced using an Applied Biosystems (Foster City, CA, USA) DNA sequencer. PCR products were generated and sequenced with primers described in Momeni et al (2000). Coding exons (3-7) were sequenced for affected individuals and unaffected individuals from each family.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, the TRPS1 gene was identified and mapped to chromosomal band 8q24.1 by Momeni et al (2000). The TRPS1 gene appears to encode a zinc-finger transcription factor, which is located proximal to the EXT1 tumor suppressor gene.…”

Section: Introductionmentioning

confidence: 99%

Analysis of novel and recurrent mutations responsible for the tricho-rhino-phalangeal syndromes

et al. 2002

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The tricho-rhino-phalangeal syndromes (TRPS type I, II, and III) are autosomal dominant disorders sharing the following characteristics: slowly growing and sparse scalp hair, medially thick and laterally thin eyebrows, bulbous tip of the nose, long flat philtrum, thin upper lip with vermilion border, and protruding ears. In addition, individuals with TRPS generally share skeletal and bone anomalies, including shortening of the phalanges and metacarpals (mild to severe brachydactyly), cone-shaped epiphyses, hip dysplasia, and short stature. The etiology of the different types of TRPS can result from either single base pair mutations, or the complete deletion of the TRPS1 gene, which encodes a zinc-finger transcription factor located on chromosomal band 8q24.1. We have identified nine heterozygous mutations, five novel and four recurrent, in unrelated families diagnosed with TRPS. The five novel mutations identified show 1-or 2-bp deletions and a single base substitution, whereas all of the recurrent mutations are single base substitutions. Seven of the nine mutations result in a premature stop codon, leading to a truncated, nonfunctional TRPS1 protein. The final two mutations are missense mutations in the GATA DNA binding zinc finger, which is believed to be important for the protein's normal function.

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“…Castration leads to increased expression of TRPS1 in rat ventral prostate (Chang et al, 2000(Chang et al, , 2002. Germline mutations in the TRPS1 gene, on the other hand, cause trichorhino-phalangeal syndrome (TRPS) types I and III (Momeni et al, 2000, Lüdecke et al, 2001). In addition, it was reported that xenopus TRPS1 acts as a repressor of the xenopus GATA4 transcription factor (Malik et al, 2001).…”

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confidence: 99%

Expression and copy number analysis of TRPS1, EIF3S3 and MYC genes in breast and prostate cancer

et al. 2004

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The long arm of chromosome 8 is one of the most common regions of amplification in cancers of several organs, especially carcinomas of the breast and prostate. TRPS1, MYC and EIF3S3 genes are located in one of the minimal regions of amplification, 8q23 -q24, and have been suggested to be the target genes of the amplification. Here, our goal was to study copy number and expression of the three genes in order to investigate the significance of the genes in breast and prostate cancer. By using fluorescence in situ hybridisation (FISH), we first found that TRPS1 and EIF3S3 were amplified together in about one-third of hormone-refractory prostate carcinomas. Next, we analysed the mRNA expression of the three genes by real-time quantitative RT -PCR and the gene copy number by FISH in six breast and five prostate cancer cell lines. Breast cancer cell line, SK-Br-3, which contained the highest copy number of all three genes, showed overexpression of only EIF3S3. Finally, the expression levels of TRPS1, EIF3S3 and MYC were measured in freshly frozen clinical samples of benign prostate hyperplasia (BPH), as well as untreated and hormone-refractory prostate carcinoma. The TRPS1 and MYC expression levels were similar in all prostate tumour groups, whereas EIF3S3 expression was higher (P ¼ 0.029) in prostate carcinomas compared to BPH. The data suggest that the expression of EIF3S3 is increased in prostate cancer, and that one of the mechanisms underlying the overexpression is the amplification of the gene.

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Mutations in a new gene, encoding a zinc-finger protein, cause tricho-rhino-phalangeal syndrome type I

Cited by 295 publications

References 17 publications

Tetraparesis due to exostotic osteochondroma at upper cervical cord in a patient with multiple exostoses–mental retardation syndrome (Langer–Giedion syndrome)

Tetraparesis due to exostotic osteochondroma at upper cervical cord in a patient with multiple exostoses–mental retardation syndrome (Langer–Giedion syndrome)

Analysis of novel and recurrent mutations responsible for the tricho-rhino-phalangeal syndromes

Expression and copy number analysis of TRPS1, EIF3S3 and MYC genes in breast and prostate cancer

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