C4ORF48, a gene from the Wolf-Hirschhorn syndrome critical region, encodes a putative neuropeptide and is expressed during neocortex and cerebellar development

Endele, Sabine; Nelkenbrecher, Claudia; Bördlein, Annegret; Schlickum, Stefanie; Winterpacht, Andreas

doi:10.1007/s10048-011-0275-8

Cited by 13 publications

(9 citation statements)

References 31 publications

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“…Nicol , a mouse ortholog of human C4orf48 , encodes a small secreted protein of unknown function (Fig. 1a ) 13 , 14 . Nicol expression is enriched in both male and female reproductive organs, including the testis, epididymis, seminal vesicles, coagulating glands, ovary, and uterus, and in various non-reproductive organs in mice, as revealed by reverse transcription-polymerase chain reaction (RT-PCR) analyses (Fig.…”

Section: Resultsmentioning

confidence: 99%

A small secreted protein NICOL regulates lumicrine-mediated sperm maturation and male fertility

et al. 2023

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The mammalian spermatozoa produced in the testis require functional maturation in the epididymis for their full competence. Epididymal sperm maturation is regulated by lumicrine signalling pathways in which testis-derived secreted signals relocate to the epididymis lumen and promote functional differentiation. However, the detailed mechanisms of lumicrine regulation are unclear. Herein, we demonstrate that a small secreted protein, NELL2-interacting cofactor for lumicrine signalling (NICOL), plays a crucial role in lumicrine signalling in mice. NICOL is expressed in male reproductive organs, including the testis, and forms a complex with the testis-secreted protein NELL2, which is transported transluminally from the testis to the epididymis. Males lacking Nicol are sterile due to impaired NELL2-mediated lumicrine signalling, leading to defective epididymal differentiation and deficient sperm maturation but can be restored by NICOL expression in testicular germ cells. Our results demonstrate how lumicrine signalling regulates epididymal function for successful sperm maturation and male fertility.

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Section: Resultsmentioning

confidence: 99%

A small secreted protein NICOL regulates lumicrine-mediated sperm maturation and male fertility

et al. 2023

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“…The following four additional genes are also located in the susceptibility region proposed in this study, fibroblast growth factor receptor 3 (FGFR3) , N-acetyltransferase 8 like (NAT8L) , DNA polymerase Nu (POLN) , and chromosome 4 open reading frame 48 (C4ORF48I) . However, these genes are not directly associated with seizures and microcephaly but have a putative involvement in the skeletal development and plasticity of the human brain [ 38 – 40 ]. In addition, previous studies have described the occurrence of seizures, microcephaly, or both, which indicates the contribution of multiple deleted genes located adjacent to the SRO delineated in our study [ 41 ].…”

Section: Resultsmentioning

confidence: 99%

Cytogenomic Integrative Network Analysis of the Critical Region Associated with Wolf-Hirschhorn Syndrome

Corrêa

Mergener

Leite

et al. 2018

BioMed Research International

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Deletions in the 4p16.3 region are associated with Wolf-Hirschhorn syndrome (WHS), a contiguous gene deletion syndrome involving variable size deletions. In this study, we perform a cytogenomic integrative analysis combining classical cytogenetic methods, fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), and systems biology strategies, to establish the cytogenomic profile involving the 4p16.3 critical region and suggest WHS-related intracellular cell signaling cascades. The cytogenetic and clinical patient profiles were evaluated. We characterized 12 terminal deletions, one interstitial deletion, two ring chromosomes, and one classical translocation 4;8. CMA allowed delineation of the deletions, which ranged from 3.7 to 25.6 Mb with breakpoints from 4p16.3 to 4p15.33. Furthermore, the smallest region of overlapping (SRO) encompassed seven genes in a terminal region of 330 kb in the 4p16.3 region, suggesting a region of susceptibility to convulsions and microcephaly. Therefore, molecular interaction networks and topological analysis were performed to understand these WHS-related symptoms. Our results suggest that specific cell signaling pathways including dopamine receptor, NAD+ nucleosidase activity, and fibroblast growth factor-activated receptor activity are associated with the diverse pathological WHS phenotypes and their symptoms. Additionally, we identified 29 hub-bottlenecks (H-B) nodes with a major role in WHS.

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“…C4orf48 gene encodes a short evolutionarily conserved protein. Endele et al (2011) had proposed that C4orf48 ( OMIM 614690 ) may be involved in the intellectual and other neurological aspects of WHS syndrome. NAT8L ( OMIM 610647 ) is a protein coding gene which has a role in regulation of lipogenesis by producing N‐acetylaspartate acid (NAA).…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic characterization of ten Egyptian patients with Wolf–Hirschhorn syndrome and review of literature

Mekkawy

Kamel

Thomas

et al. 2020

Molec Gen & Gen Med

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Background Wolf–Hirschhorn syndrome (WHS) (OMIM 194190) is a multiple congenital anomalies/intellectual disability syndrome. It is caused by partial loss of genetic material from the distal portion of the short arm of chromosome. Methods We studied the phenotype–genotype correlation. Results We present the clinical manifestations and cytogenetic results of 10 unrelated Egyptian patients with 4p deletions. Karyotyping, FISH and MLPA was performed for screening for microdeletion syndromes. Array CGH was done for two patients. All patients exhibited the cardinal clinical manifestation of WHS. FISH proved deletion of the specific WHS locus in all patients. MLPA detected microdeletion of the specific locus in two patients with normal karyotypes, while array CGH, performed for two patients, has delineated the extent of the deleted segments and the involved genes. LETM1, the main candidate gene for the seizure phenotype, was found deleted in the two patients tested by array CGH; nevertheless, one of them did not manifest seizures. The study emphasized the previous. Conclusion WHS is a contiguous gene syndrome resulting from hemizygosity of the terminal 2 Mb of 4p16.3 region. The Branchial fistula, detected in one of our patients is a new finding that, to our knowledge, was not reported.

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C4ORF48, a gene from the Wolf-Hirschhorn syndrome critical region, encodes a putative neuropeptide and is expressed during neocortex and cerebellar development

Cited by 13 publications

References 31 publications

A small secreted protein NICOL regulates lumicrine-mediated sperm maturation and male fertility

A small secreted protein NICOL regulates lumicrine-mediated sperm maturation and male fertility

Cytogenomic Integrative Network Analysis of the Critical Region Associated with Wolf-Hirschhorn Syndrome

Clinical and genetic characterization of ten Egyptian patients with Wolf–Hirschhorn syndrome and review of literature

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