The SRY-related (SOX) transcription factor family pivotally contributes to determining cell fate and identity in many lineages. Since the original discovery that SRY deletions cause sex reversal, mutations in half of the 20 human SOX genes have been associated with rare congenital disorders, henceforward called SOXopathies. Mutations are generally de novo, heterozygous, and inactivating, revealing gene haploinsufficiency, but other types, including duplications, have been reported too. Missense variants primarily target the HMG domain, the SOX hallmark that mediates DNA binding and bending, nuclear trafficking, and protein-protein interactions. We here review key clinical and molecular features of SOXopathies and discuss the prospect that the disease family likely involves more SOX genes and larger clinical and genetic spectrums than currently appreciated.

中文翻译：

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SOX病：由于SOX突变而导致的发育障碍家族不断增加。

SRY相关（SOX）转录因子家族对确定许多谱系中的细胞命运和特性至关重要。由于最初发现SRY缺失会导致性逆转，因此20种人类SOX基因中有一半的突变与罕见的先天性疾病有关，因此被称为SOXopathies。突变通常是从头开始的，杂合的和失活的，揭示了基因单倍体不足，但是也已经报道了其他类型，包括重复。Missense变体主要针对HMG结构域，SOX标志介导DNA结合和弯曲，核运输和蛋白质-蛋白质相互作用。