METHODS: This report describes two cases with homozygous loss- of- function variants in NOTCH3 along with their clinical manifestations.
RESULTS: These patients presented with a severe congenital phenotype, including eye misalignment, visual impairment, epilepsy, global developmental delay, and subsequent development of pyramidal signs. Biallelic nonsense variants were discovered in both the cases (NM_000435.3:c.2203 C > T (p. [Arg735Ter]). Livedo reticularis was not reported in our cases, although it was present in previously reported patients. Autosomal recessive NOTCH3-related leukodystrophy is usually caused by biallelic null mutations in NOTCH3.
CONCLUSIONS: The phenotype of biallelic null variants is associated with a more severe phenotype than the dominantly inherited form of the disease.
方法:本报告描述了2例NOTCH3纯合功能缺失变异的病例及其临床表现。
结果:这些患者表现为严重的先天性表型,包括眼睛错位,视力障碍,癫痫,全球发育迟缓,和随后发展的金字塔的迹象。在两种情况下都发现了双等位基因无义变体(NM_000435.3:c.2203C>T(p。[Arg735Ter]).在我们的病例中没有报告网状Livedo,尽管它存在于以前报道的患者中。常染色体隐性遗传NOTCH3相关的脑白质营养不良通常由NOTCH3的双等位基因无效突变引起。
结论:双等位基因无效变异体的表型与比显性遗传形式更严重的表型相关。