PDF(Pubmed)
Abstract：
Pubertal delay can be due to hypogonadotropic hypogonadism (HH), which may occur in association with anosmia or hyposmia and is known as Kallmann syndrome (OMIM #308700). Recently, hypogonadotropic hypogonadism has been suggested to overlap with Witteveen-Kolk syndrome (WITKOS, OMIM #613406) associated with 15q24 microdeletions encompassing SIN3A. Whether hypogonadotropic hypogonadism is due to haploinsufficiency of SIN3A or any of the other eight genes present in 15q24 is not known. We report the case of a female patient with delayed puberty associated with intellectual disability, behavior problems, dysmorphic facial features, and short stature, at the age of 14 years. Clinical, laboratory, and imaging assessments confirmed the diagnosis of Kallmann syndrome. Whole-exome sequencing identified a novel heterozygous frameshift variant, NM_001145358.2:c.3045_3046dup, NP_001138830.1:p.(Ile1016Argfs*6) in SIN3A, classified as pathogenic according to the American College of Medical Genetics and Genomics (ACMG/AMP) criteria. Reverse phenotyping led to the clinical diagnosis of WITKOS. No other variant was found in the 96 genes potentially related to hypogonadotropic hypogonadism. The analysis of the other contiguous seven genes to SIN3A in 15q24 did not reveal any clinically relevant variant. In conclusion, these findings point to SIN3A as the gene in 15q24 related to the reproductive phenotype in patients with overlapping WITKOS and Kallmann syndrome.
摘要：
青春期延迟可能是由于低促性腺激素性性腺功能减退症（HH），可能与嗅觉缺失或嗅觉减退有关，被称为Kallmann综合征（OMIM#308700）。最近,低促性腺激素性性腺功能减退被认为与Witteveen-Kolk综合征重叠(WITKOS，OMIM#613406)与包含SIN3A的15q24微缺失相关。尚不清楚低促性腺激素性性腺功能减退是否归因于SIN3A或15q24中存在的其他八个基因中的任何一个的单倍体不足。我们报告了一例女性患者的青春期延迟与智力障碍有关，行为问题,畸形面部特征，身材矮小，在14岁的时候。临床,实验室,影像学评估证实了Kallmann综合征的诊断。全外显子组测序鉴定了一种新的杂合移码变体，NM_001145358.2：c.3045_3046dup，NP_001138830.1：p。(Ile1016Argfs*6)在SIN3A中，根据美国医学遗传学和基因组学学院(ACMG/AMP)标准分类为致病性。反向表型导致WITKOS的临床诊断。在可能与低促性腺激素性性腺功能减退有关的96个基因中未发现其他变体。对15q24中SIN3A的其他连续七个基因的分析未揭示任何临床相关变体。总之,这些发现表明SIN3A是15q24中与WITKOS和Kallmann综合征重叠患者生殖表型相关的基因.
