Vascular Malformations Section, Institute of Medical and Molecular Genetics, INGEMM-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.
Bioinformatics Section, Institute of Medical and Molecular Genetics, INGEMM-IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.
Genet Med. 2018 Aug;20(8):882-889. doi: 10.1038/gim.2017.200. Epub 2018 Feb 15.
CLAPO syndrome is a rare vascular disorder characterized by capillary malformation of the lower lip, lymphatic malformation predominant on the face and neck, asymmetry, and partial/generalized overgrowth. Here we tested the hypothesis that, although the genetic cause is not known, the tissue distribution of the clinical manifestations in CLAPO seems to follow a pattern of somatic mosaicism.
We clinically evaluated a cohort of 13 patients with CLAPO and screened 20 DNA blood/tissue samples from 9 patients using high-throughput, deep sequencing.
We identified five activating mutations in the PIK3CA gene in affected tissues from 6 of the 9 patients studied; one of the variants (NM_006218.2:c.248T>C; p.Phe83Ser) has not been previously described in developmental disorders.
We describe for the first time the presence of somatic activating PIK3CA mutations in patients with CLAPO. We also report an update of the phenotype and natural history of the syndrome.
CLAPO 综合征是一种罕见的血管疾病，其特征为下唇毛细血管畸形、面颈部淋巴管畸形为主、不对称和部分/全身性过度生长。在这里，我们假设虽然遗传原因尚不清楚，但 CLAPO 临床表现的组织分布似乎遵循体马赛克模式。
我们对 13 名 CLAPO 患者进行了临床评估，并对 9 名患者中的 20 份 DNA 血液/组织样本进行了高通量、深度测序筛查。
我们在 6 名研究患者的受累组织中发现了 PIK3CA 基因的五个激活突变；其中一种变体（NM_006218.2:c.248T>C；p.Phe83Ser）以前在发育障碍中未被描述过。
我们首次描述了 CLAPO 患者存在体细胞激活 PIK3CA 突变。我们还报告了该综合征表型和自然史的更新。
