期刊论文详细信息
BMC Medical Genetics
A 16q deletion involving FOXF1 enhancer is associated to pulmonary capillary hemangiomatosis
Giuseppe Damante3  Stefano Pizzolitto2  Luigi Cattarossi1  Carla Pittini1  Giovanna De Maglio2  Cinzia Puppin3  Federica Baldan3  Alessandra Franzoni2  Patrizia Dello Russo2 
[1]Dipartimento Materno-infantile, Azienda Ospedaliero-Universitaria S. Maria della Misericordia, Udine, Italy
[2]Dipartimento di Medicina di Laboratorio, Azienda Ospedaliero-Universitaria S. Maria della Misericordia, Udine, Italy
[3]Dipartimento di Scienze Mediche e Biologiche, Università di Udine, Piazzale Kolbe 4, Udine, 33100, Italy
关键词: Gene regulation;    Deletion;    Chromosomal abnormalities;    Pulmonary capillary hemangiomatosis;   
Others  :  1230638
DOI  :  10.1186/s12881-015-0241-7
 received in 2015-07-04, accepted in 2015-10-04, published in 16
PDF
【 摘 要 】

Background

Pulmonary capillary hemangiomatosis (PCH) is an uncommon pulmonary disorder, with variable clinical features depending on which lung structure is affected, and it is usually linked to pulmonary arterial hypertension. Congenital PCH has been very rarely described and, so far, the only causative gene identified is EIF2AK4, which encodes for a translation initiation factor. However, not all PCH cases might carry a mutation in this gene.

Case presentation

We report the clinical and cytogenetic characterization of a patient (male, newborn, first child of healthy non-consanguineous parents) died after three days of life with severe neonatal pulmonary hypertension, due to diffuse capillary hemangiomatosis diagnosed post mortem.

Conventional karyotyping, Microarray-Based Comparative Genomic Hydridization (CGHa) and quantitative PCR were performed. CGHa revealed a heterozygous chromosome 16q23.3q24.1 interstitial deletion, spanning about 2.6 Mb and involving a FOXF1 gene enhancer. Quantitative PCR showed that the proband’s deletion was de novo. Microsatellite analysis demonstrate that the deletion occurred in the maternal chromosome 16.

Conclusion

FOXF1 loss of function mutation have been so far identified in alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), a lung disease different from PCH. Our data suggest the hypothesis that disruption of the FOXF1 gene enhancer could be a genetic determinant of PCH. Moreover, our findings support the idea that FOXF1 is a paternally imprinted gene.

【 授权许可】

   
2015 Dello Russo et al.

【 预 览 】
附件列表
Files Size Format View
20151107022644737.pdf 1703KB PDF download
Fig. 4. 38KB Image download
Fig. 3. 22KB Image download
Fig. 2. 35KB Image download
Fig. 1. 132KB Image download
【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

【 参考文献 】
  • [1]Folkman J, Klagsbrun M. Angiogenic factors. Science. 1987; 235:442-7.
  • [2]Langleben D, Montreal MD. Pulmonary capillary hemangiomatosis: the puzzle takes shape. Chest. 2014; 145:197-9.
  • [3]Wirbelauer J, Hebestreit H, Eugene AM, Mark J, Speer CP. Familial pulmonary capillary hemangiomatosis early in life. Case Rep Pulmonol. 2011.
  • [4]Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A et al.. Clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013; 62:D34-41.
  • [5]Oviedo A, Abramson LP, Worthington R, Dainauskas JR, Crawford SE. Congenital pulmonary capillary hemangiomatosis: report of two cases and review of literature. Pediatr Pulmonol. 2003; 36:253-6.
  • [6]Best DH, Sumner KL, Austin ED, Chung WK, Brown LM, Borczuk AC et al.. EIF2AK4 mutations in pulmonary capillary hemangiomatosis. Chest. 2014; 145:231-6.
  • [7]Szafranski P, Dharmadhikari AV, Brosens E, Gurha P, Kolodziejska KE, Zhishuo O et al.. Small noncoding differentially methylated copy-number variants, including lncRNA genes, cause a lethal lung developmental disorder. Genome Res. 2013; 23:23-33.
  • [8]Wagenvoort CA. Misalignment of lung vessels: a syndrome causing persistent neonatal pulmonary hypertension. Hum Pathol. 1986; 17:727-30.
  • [9]Sen P, Thakur N, Stockton DW, Langston C, Bejjani BA. Expanding the phenotype of alveolar capillary dysplasia (ACD). J Pediatr. 2004; 145:646-51.
  • [10]Sen P, Gerychova R, Janku P, Jezova M, Valaskova I, Navarro C et al.. A familial case of alveolar capillary dysplasia with misalignment of pulmonary veins supports paternal imprinting of FOXF1 in human. Eur J Hum Genet. 2013; 21:474-7.
  • [11]Hung S-P, Huang S-H, Wu C-H, Chen W-C, Kou K-E, Wang N-K, Lin L-H. Misaligment of lung vessels and alveolar capillary dysplasia: a case report with autopsy. Pediatr Neonatol. 2011; 52:232-6.
  • [12]Michalsky MP, Arca MJ, Freek G, Sue H, Dick T, Caniano DA. Alveolar capillary dysplasia: a logical approach to a fatal disease. J Pediatr Surg. 2005; 40:1100-5.
  • [13]Nouri-Merchaoui S, Mahdhaoui N, Yacoubi M-T, Seboul H. Congenital pulmonary lymphangiectasis: an unusual cause of respiratory distress in neonates. Arch Pediatr. 2012; 19:408-12.
  • [14]Szafranski P, Dharmadhikari AV, Wambach JA, Towe CT, White FV, Grady RM et al.. Two deletions overlapping a distant FOXF1 enhancer unravel the role of lncRNA LINC01081 in etiology of alveolar capillary dysplasia with misalignment of pulmonary veins. Am J Med Genet A. 2014; 164A:2013-9.
  • [15]Tamura M, Sasaki Y, Koyama R, Takeda K, Idogawa M, Tokino T. Forkhead transcription factor FOXF1 is a novel target gene of the p53 family and regulates cancer cell migration and invasiveness. Oncogene. 2014; 2:4837-46.
  • [16]Lo PK, Lee JS, Liang X, Han L, Mori T, Fackler MJ et al.. Epigenetic inactivation of the potential tumor suppressor gene FOXF1 in breast cancer. Cancer Res. 2010; 70:6047-58.
  • [17]Wei HJ, Nickoloff JA, Chen WH, Liu HY, Lo WC, Chang YT et al.. FOXF1 mediates mesenchymal stem cell fusion-induced reprogramming of lung cancer cells. Oncotarget. 2014; 19:9514-29.
  • [18]Wagenvoort CA, Beetstra A, Spijker J. Capillary haemangiomatosis of the lungs. Histopathology. 1978; 6:401-6.
  • [19]Stankiewicz P, Sen P, Bhatt SS, Storer M, Xia Z, Bejjani BA et al.. Genomic and genic deletions of the FOX gene cluster on 16q24.1 and inactivating mutations of FOXF1 cause alveolar capillary dysplasia and other malformations. Am J Hum Genet. 2009; 84:780-91.
  文献评价指标  
  下载次数:20次 浏览次数:1次