Bamborschke Daniel, Pergande Matthias, Becker Kerstin, Koerber Friederike, Dötsch Jörg, Vierzig Anne, Weber Lutz T, Cirak Sebahattin
Center for Molecular Medicine Cologne, Cologne, Germany; Department of Pediatrics, University Hospital of Cologne, Cologne, Germany.
Department of Pediatric Radiology, University Hospital of Cologne, Cologne, Germany.
Brain Dev. 2018 Jun;40(6):480-483. doi: 10.1016/j.braindev.2018.02.008. Epub 2018 Mar 2.
Recently recessive mutations in sphingosine-1-phosphate lyase (SGPL1) have been published as a cause of syndromic congenital nephrotic syndrome with adrenal insufficiency. We have identified a case with fetal hydrops and brain malformations due to a mutation in SGPL1.
We report a patient presenting with severe fetal hydrops, congenital nephrotic syndrome and adrenal calcifications. MRI imaging showed generalized cortical atrophy with simplified gyral pattern and hypoplastic temporal lobes as well as cerebellar hypoplasia and hyperintensity in the pons. The boy deceased at 6 weeks of age. Via whole exome sequencing, we identified a novel homozygous frameshift mutation c.1233delC (p.Phe411Leufs56) in SGPL1.
In our patient, we describe a novel mutation in sphingosine-1-phosphate lyase (SGPL1) leading to severe brain malformation. Neurodevelopmental phenotypes have been reported earlier, but not described in detail. To this end, we present a review on all published SGPL1-mutations and genotype-phenotype correlations focusing on neurodevelopmental outcomes. We hypothesized on the severe neurological phenotypes, which might be due to disruption of neuronal autophagy. Mutations in SGPL1 shall be considered in the differential diagnosis of fetal hydrops as well as congenital brain malformations and neuropathies.
最近有研究报道，鞘氨醇-1-磷酸裂解酶（SGPL1）的隐性突变是导致伴有肾上腺功能不全的综合征性先天性肾病综合征的原因。我们发现了一例因SGPL1突变导致胎儿水肿和脑畸形的病例。
我们报告了一名患有严重胎儿水肿、先天性肾病综合征和肾上腺钙化的患者。MRI成像显示广泛性皮质萎缩，脑回模式简化，颞叶发育不全，以及小脑发育不全和脑桥高信号。该男婴在6周龄时死亡。通过全外显子组测序，我们在SGPL1中发现了一个新的纯合移码突变c.1233delC（p.Phe411Leufs56）。
在我们的患者中，我们描述了一种鞘氨醇-1-磷酸裂解酶（SGPL1）的新突变，该突变导致严重的脑畸形。此前已有神经发育表型的报道，但未详细描述。为此，我们对所有已发表的SGPL1突变以及关注神经发育结果的基因型-表型相关性进行了综述。我们推测严重的神经表型可能是由于神经元自噬的破坏所致。在胎儿水肿以及先天性脑畸形和神经病变的鉴别诊断中应考虑SGPL1突变。
