This report is regarding a Dutch female with microcephaly, mild intellectual disability (ID), gonadal dysgenesis and dysmorphic facial features with synophrys. Upon genotyping, an ~455 kb de novo deletion encompassing the first exon of NRXN1 was found. Bidirectional sequencing of the coding exons of the NRXN1 alpha isoform was subsequently performed to investigate the possibility of a pathogenic mutation on the other allele, but we could not find any other mutation. Previously, many heterozygous mutations as well as microdeletions in NRXN1 were shown to be associated with ID, autism, schizophrenia, and other psychiatric and psychotic disorders. Our results are in agreement with other reports that show that NRXN1 deletions can lead to ID, microcephaly and mild dysmorphic features. However, this is the first report of gonadal dysgenesis being associated with such deletions. It is not clear whether there is a causal relationship between the NRXN1 deletion and gonadal dysgenesis, but it is of interest that the FSHR gene, which encodes the follicle-stimulating hormone receptor causative correlation that is mutated in ovarian dysgenesis, is located proximal to the NRXN1 gene. Given that most of the females carrying NRXN1 deletions have been diagnosed at a prepubertal age, gynecologic screening of female carriers of a NRXN1 deletion is warranted.

中文翻译：

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荷兰轻度智力障碍，小头畸形和性腺发育不全患者的NRXN1从头微缺失。

这份报告是关于一名荷兰女性，患有小头畸形，轻度智力障碍（ID），性腺发育不全和面部视神经功能异常。基因分型后，发现一个〜455 kb的从头缺失，涵盖NRXN1的第一个外显子。随后对NRXN1α亚型的编码外显子进行了双向测序，以研究在其他等位基因上发生致病性突变的可能性，但我们找不到任何其他突变。以前，NRXN1中的许多杂合突变和微缺失已显示出与ID，自闭症，精神分裂症以及其他精神病和精神病性疾病有关。我们的结果与其他报告一致，这些报告显示NRXN1缺失可导致ID，小头畸形和轻度畸形。然而，这是与这种缺失有关的性腺发育不全的首次报道。目前尚不清楚NRXN1缺失与性腺发育不全之间是否存在因果关系，但是有趣的是，编码卵泡刺激性生殖失调的促卵泡激素受体因果关系的FSHR基因位于卵巢近端。 NRXN1基因。鉴于大多数携带NRXN1缺失的女性均已在青春期前被诊断出，因此有必要对女性携带NRXN1缺失的女性进行筛查。位于NRXN1基因的近端。鉴于大多数携带NRXN1缺失的女性均已在青春期前被诊断出，因此有必要对女性携带NRXN1缺失的女性进行筛查。位于NRXN1基因的近端。鉴于大多数携带NRXN1缺失的女性均已在青春期前被诊断出，因此有必要对女性携带NRXN1缺失的女性进行筛查。