Rutgers New Jersey Medical School, New Jersey, USA.
Division of Endocrinology, Department of Pediatrics, Rutgers New Jersey Medical School, New Jersey, USA.
Am J Med Genet A. 2020 Dec;182(12):2887-2890. doi: 10.1002/ajmg.a.61860. Epub 2020 Sep 19.
Differences in sex development (DSD) are a group of rare conditions involving genes, hormones and reproductive organs, including genitals. Although these disorders are common, information about the molecular causes remain limited. Many genes have been identified in association with DSD but in many cases the causative gene could not be identified. The Lhx9 gene has been studied in mice and birds, and biallelic mutations in this gene have been found to cause 46,XY DSD and limb abnormalities. So far two variants of LHX9 have been identified in 46,XY individuals with testicular regression, micropenis and hypospadias. We report a de novo heterozygous missense variant in LHX9 in a girl with 46,XY DSD and finger and toe abnormalities. It was previously predicted that a mutation in LHX9 would not cause extragenital anomalies in light of prior animal studies, but our report adds to the limited knowledge of the phenotype observed in humans with a variant in LHX9. To the best of our knowledge this is the first reported case with this combination of abnormalities.
性发育差异（DSD）是一组涉及基因、激素和生殖器官（包括生殖器）的罕见病症。尽管这些疾病很常见，但有关其分子病因的信息仍然有限。许多基因已被确定与 DSD 相关，但在许多情况下，无法确定致病基因。Lhx9 基因已在小鼠和鸟类中进行了研究，该基因的双等位基因突变已被发现可导致 46,XY DSD 和肢体异常。迄今为止，已有两名睾丸退化、小阴茎和尿道下裂的 46,XY 个体中鉴定出 LHX9 的两种变体。我们报告了一名 46,XY DSD 合并手指和脚趾异常女孩的 LHX9 中存在新生杂合错义变异。鉴于先前的动物研究，先前预测 LHX9 中的突变不会导致外生殖器异常，但我们的报告增加了有限的知识，即人类中存在 LHX9 变异时观察到的表型。据我们所知，这是首例具有这种异常组合的报道病例。
