Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut, USA.
Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
J Cutan Pathol. 2020 Aug;47(8):681-685. doi: 10.1111/cup.13683. Epub 2020 Apr 6.
Congenital smooth muscle hamartomas (CSMHs) are benign lesions that share clinical and histopathological features with Becker nevus, a mosaic disorder associated with post-zygotic ACTB mutations. Given the clinical and histopathological overlap between CSMH and Becker nevus, we hypothesized that post-zygotic mutations in ACTB may underlie CSMH.
Direct sequencing of ACTB gene in affected and unaffected tissue isolated from one case of hemihypertrichosis and hemihypertrophy corresponding to giant segmental CSMH and hemihypertrophy. This was followed by direct sequencing with and without enrichment assay for hotspot ACTB mutations in affected tissue from 12 samples of isolated CSMH from unrelated individuals.
In total we identified somatic missense ACTB mutations in 9 out of 13 CSMHs (69%). Mutations were either novel or previously reported in Becker nevi and Becker nevus syndrome.
CSMHs result from post-zygotic ACTB mutations. This study proves that CSMHs and Becker nevi are nosologically related, and expand the phenotypic spectrum of ACTB mutations.
先天性平滑肌错构瘤（CSMH）是一种良性病变，其临床和组织病理学特征与贝克痣（Becker nevus）相似，贝克痣是一种与合子后 ACTB 突变相关的嵌合体疾病。鉴于 CSMH 和贝克痣在临床和组织病理学上的重叠，我们假设 ACTB 中的合子后突变可能是 CSMH 的基础。
对一例相应于巨大节段性 CSMH 和肥大的单侧性过度生长的单侧性过度生长和肥大的组织中分离的受影响和未受影响的组织中的 ACTB 基因进行直接测序。然后，对 12 例来自无关个体的孤立性 CSMH 受影响组织进行了 ACTB 热点突变的直接测序和富集检测。
在总共 13 例 CSMH 中有 9 例（69%）发现了体细胞错义 ACTB 突变。突变要么是新的，要么是以前在贝克痣和贝克痣综合征中报道过的。
CSMH 是由合子后 ACTB 突变引起的。本研究证明 CSMH 和贝克痣在疾病分类学上是相关的，并扩展了 ACTB 突变的表型谱。
