Constitutional mosaicism in RASA1-related capillary malformation-arteriovenous malformation

被引:14
作者
Gordo, Gema [1 ]
Rodriguez-Laguna, Lara [1 ]
Agra, Noelia [1 ]
Mendez, Pilar [2 ]
Feito, Marta [3 ]
Lapunzina, Pablo [4 ,5 ]
Lopez-Gutierrez, Juan C. [6 ]
Martinez-Glez, Victor [1 ,4 ,5 ]
机构
[1] Hosp Univ La Paz, Vasc Malformat Sect, Inst Med & Mol Genet, INGEMM,IdiPAZ, Madrid, Spain
[2] Complejo Hosp Univ Badajoz, Unidad Genet, Serv Inmunol & Genet, Badajoz, Spain
[3] Hosp Univ La Paz, Dept Dermatol, Madrid, Spain
[4] Hosp Univ La Paz, Clin Genet Sect, Inst Med & Mol Genet, INGEMM,IdiPAZ, Madrid, Spain
[5] ISCIII, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
[6] Hosp Univ La Paz, Vasc Anomalies Ctr Plast Surg, Madrid, Spain
关键词
capillary malformation-arteriovenous malformation; constitutional mosaicism; RASA1; RASA1; MUTATIONS;
D O I
10.1111/cge.13499
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Capillary malformation-arteriovenous malformation (CM-AVM) is caused by germline RASA1 and EPHB4 alterations. RASA1 intralesional second hits have also been reported. Here we report RASA1 constitutional mosaicism, defined here as the presence of a mosaic variant in all cell types of an individual, in two patients with CM-AVM. High-throughput sequencing was used to search for RASA1 pathogenic variants in blood samples from two unrelated patients with CM-AVM. An affected tissue sample from one of the patients was also analyzed. Both patients showed different nonsense RASA1 variants in mosaic, ranging from 7% to 21.5%, in blood samples and in the corresponding affected tissue sample from one of the patients. In conclusion, we report for the first time the presence of RASA1 constitutional mosaicism in CM-AVM. Constitutional mosaicism has implications for accurate molecular diagnosis and recurrence risk and helps to explain the great phenotypic variability in CM-AVM.
引用
收藏
页码:516 / 519
页数:4
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