Expression of CUL7 and CCDC8 proteins in normal mouse tibial growth plate / 中华内分泌代谢杂志

To investigate the changes of expression location and amount of CUL7 and CCDC8 proteins in the growth plate of normal mice aged 0-4 weeks, and to clarify the roles of CUL7 and CCDC8 proteins in the proliferation and differentiation of tibia growth plate of mice. The expression location and levels of CUL7 and CCDC8 proteins in the tibial growth plate of normal mice aged 0-4 weeks were observed with immunohistochemical staining. CUL7 protein was expressed in the cell cytoplasm and membrane in three zones of tibial growth plate three bands at 0-4 weeks. The expression level and total expression level of CUL7 protein in each zone of growth plate decreased gradually with the increase of week of age( F=369.61, P=0.001). The expression of CUL7 protein decreased most significantly in the proliferative zone, followed by the stationary zone and the hypertrophic zone. CCDC8 protein was mainly expressed in proliferation zone and hypertrophic zone cell membrane and nuclear membrane of growth plate at 0-2 weeks, and mainly expressed in hypertrophic zone cell membrane and nuclear membrane at 3-4 weeks. The expression of CCDC8 protein in the proliferating zone changed inversely with week of age, and the expression of CCDC8 protein in the hypertrophic zone increased over 4 weeks( F=453.67, P<0.001). The total expression of CCDC8 protein in growth plates decreased with the increase of week of age.The expression levels of CUL7 and CCDC8 decreased with the increase of week of age, suggesting that CUL7 and CCDC8 may promote the proliferation and differentiation of growth plate chondrocytes.

Novel mutation in Cul7 gene in a family diagnosed with 3M syndrome

This study evaluates a family with two siblings having severe growth retardation and facial dysmorphism, born to consanguineous normal healthy parents. Affymetrix CytoScan 750K microarray showed a 34-Mb pericentric homozygous region on chromosome 6 for both siblings. CUL7 was one of the 141 genes present in this region. Sanger sequencing of CUL7 gene detected a 2-bp novel deletion in the 15th exon (c.2943_2944delCT of the cDNA). This deletion leads to a frameshift and a premature termination signal much upstream of the wild-type termination signal, leading to a nonsense mediated decay of the mRNA. CUL7 protein plays an important role in formation of 3M complex, ubiquitination, microtubule dynamics and cell cycle regulation. Mutations in CUL7 gene is known to cause a rare 3M syndrome. Information about the novel mutation has been accepted in the ClinVar database with rs1064792895.

3M syndrome: a case report and literature review / 临床儿科杂志

Objective To investigate the clinical features and gene mutations of 3M syndrome. Method The clinical data of a child with 3M syndrome was retrospectively analyzed. The DNA was extracted from the peripheral blood of the child and parents, and the sequence analyses were performed by Agilent SureSelect exon capture and Illumina HiSeq sequencing platform. And the mutant gene was validated by Sanger sequencing. Results The six-month-old girl presented special face and growth retardation.The girl had a missense mutation c.4898C>T,p.T1633M in the CUL7 gene(NM_014780.4),and both her parents had heterozygous mutations.The girl was diagnosed with 3M syndrome.Conclusions The CUL7 mutation is the major causative gene of 3M syndrome in this girl. Early gene testing should be performed to confirm the diagnosis in suspected clinical phenotype.