Chromosome 13q deletion with Waardenburg syndrome: further evidence for a gene involved in neural crest function on 13q.

Camp, Guy Van; Thienen, M N Van; Handig, I; Roy, Bernadette Van; Rao, V. Sree Hari; Milunsky, Aubrey; Read, Andrew P.; Baldwin, Clinton T.; Farrer, Lindsay A.; Bonduelle, M

doi:10.1136/jmg.32.7.531

Cited by 42 publications

(29 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…34 Hirschsprung disease has been reported in other patients with an interstitial deletion involving the region 13q22. 8,27,28,35,36 The milder form of constipation without evidence of intestinal aganglionosis seen in the reported patients may be explained by regulatory effects.…”

mentioning

confidence: 93%

Genotype–phenotype correlations in patients with retinoblastoma and interstitial 13q deletions

et al. 2011

View full text Add to dashboard Cite

Patients with an interstitial 13q deletion that contains the RB1 gene show retinoblastoma and variable clinical features. Relationship between phenotypic expression and loss of specific neighboring genes are unresolved, yet. We obtained clinical, cytogenetic and molecular data in 63 patients with an interstitial 13q deletion involving RB1. Whole-genome array analysis or customized high-resolution array analysis for 13q14.11q14.3 was performed in 38 patients, and cytogenetic analysis was performed in 54 patients. Deletion sizes ranged between 4.2 kb and more than 33.43 Mb; breakpoints were non-recurrent. Sequence analysis of deletion junctions in five patients revealed microhomology and insertion of 2-34 base pairs suggestive of non-homologous end joining. Milder phenotypic expression of retinoblastoma was observed in patients with deletions larger than 1 Mb, which contained the MED4 gene. Clinical features were compared between patients with small (within 13q14), medium (within 13q12.3q21.2) and large (within 13q12q31.2) deletions. Patients with a small deletion can show macrocephaly, tall stature, obesity, motor and/or speech delay. Patients with a medium deletion show characteristic facial features, mild to moderate psychomotor delay, short stature and microcephaly. Patients with a large deletion have characteristic craniofacial dysmorphism, short stature, microcephaly, mild to severe psychomotor delay, hypotonia, constipation and feeding problems. Additional features included deafness, seizures and brain and heart anomalies. We found no correlation between clinical features and parental origin of the deletion. Our data suggest that hemizygous loss of NUFIP1 and PCDH8 may contribute to psychomotor delay, deletion of MTLR1 to microcephaly and loss of EDNRB to feeding difficulties and deafness.

show abstract

mentioning

confidence: 93%

Genotype–phenotype correlations in patients with retinoblastoma and interstitial 13q deletions

et al. 2011

View full text Add to dashboard Cite

show abstract

“…13,14 Through binding to the specific recognition motif, that is, the M box sequence (CATGTG), Mitf enhances transcription of the genes encoding major enzymes in the melanin synthesis pathway, including tyrosinase, 15,16 tyrosinase-related protein 1 (TRP-1), 16 TRP-2 11 and dopachrome tautomerase 17 as well as other melanogenic genes, such as SILV/PMEL17/GP100 and MLANA/MART-1. 18 Mutations in the Mitf gene result in the loss or anomaly of pigmentation in mouse 8,19 and human 20,21 owing to aberrant differentiation of melanocytes. It has also been reported that fibroblasts genetically transfected with Mitf develop into cells with characteristics of melanocytes.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic RNA interference of malignant melanoma by electrotransfer of small interfering RNA targeting Mitf

et al. 2006

View full text Add to dashboard Cite

Microphthalmia-associated transcription factor (Mitf) is critically involved in melanin synthesis as well as differentiation of cells of the melanocytic lineage. Some earlier studies suggested that Mitf is also essential in the survival of melanoma cells, but this notion remains controversial. We synthesized short interfering RNA (siRNA) duplexes corresponding to the mitf sequence and transfected them into B16 melanoma. Lipid-mediated transfection in vitro of Mitfspecific siRNA resulted in specific downregulation of Mitf and of the tyrosinase that is a transcriptional target of Mitf. This treatment also remarkably reduced the viability of melanoma cells by inducing apoptosis. To examine the potential feasibility of RNAi therapy against melanoma, B16 cells were subcutaneously injected into syngenic mice and siRNA was transfected into the pre-established tumor by means of electroporation. The Mitf-specific siRNA drastically reduced outgrowth of subcutaneous melanoma, while nonspecific siRNA failed to affect tumor progression. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-based analysis of tumor specimens demonstrated that the tumor cells transfected with Mitf-siRNA effectively underwent apoptosis in vivo. The present results indicate that Mitf plays important roles in melanoma survival. Intratumor electrotransfer of Mitf-specific siRNA may provide a powerful strategy for therapeutic intervention of malignant melanoma.

show abstract

“…Specific mutations within a number of PAX/ Pax (human/mouse) genes lead to a range of developmental abnormalities in both human beings and mouse. Many studies proved that PAX3 loss of function mutations are involved in either type 1 or type 3 Waardenburg syndrome [59][60][61][62][63][64][65]. PAX3/Pax3 (human/mouse) mutations are associated with limb muscle hypoplasia in Waardenburg syndrome patients and Splotch phenotype mice, respectively [54,55].…”

Section: Pax3 and Its Role In Development And Diseasesmentioning

confidence: 99%

PAX3: A Molecule with Oncogenic or Tumor Suppressor Function Is Involved in Cancer

Arasu

Murugan

Essa

et al. 2018

BioMed Research International

View full text Add to dashboard Cite

Metastasis is the most deadly aspect of cancer and results from acquired gene regulation abnormalities in tumor cells. Transcriptional regulation is an essential component of controlling of gene function and its failure could contribute to tumor progression and metastasis. During cancer progression, deregulation of oncogenic or tumor suppressive transcription factors, as well as master cell fate regulators, collectively influences multiple steps of the metastasis cascade, including local invasion and dissemination of the tumor to distant organs. Transcription factor PAX3/Pax3, which contributes to diverse cell lineages during embryonic development, plays a major role in tumorigenesis. Mutations in this gene can cause neurodevelopmental disease and the existing literature supports that there is a potential link between aberrant expression of PAX3 genes in adult tissues and a wide variety of cancers. PAX3 function is tissue-specific and could contribute to tumorigenesis either directly as oncogene or as a tumor suppressor by losing its function. In this review, we discuss comprehensively the differential role played by PAX3 in various tissues and how its aberrant expression is implicated in disease development. This review particularly highlights the oncogenic and tumor suppressor role played by PAX3 in different cancers and underlines the importance of precisely identifying tissue-specific role of PAX3 in order to determine its exact role in development of cancer.

show abstract

Chromosome 13q deletion with Waardenburg syndrome: further evidence for a gene involved in neural crest function on 13q.

Cited by 42 publications

References 40 publications

Genotype–phenotype correlations in patients with retinoblastoma and interstitial 13q deletions

Genotype–phenotype correlations in patients with retinoblastoma and interstitial 13q deletions

Therapeutic RNA interference of malignant melanoma by electrotransfer of small interfering RNA targeting Mitf

PAX3: A Molecule with Oncogenic or Tumor Suppressor Function Is Involved in Cancer

Contact Info

Product

Resources

About