Aslanger Ayca Dilruba, Demiral Emine, Sonmez-Sahin Seyma, Guler Serhat, Goncu Beyza, Yucesan Emrah, Iscan Akın, Saltik Sema, Yesil Gozde
Department of Medical Genetics, Faculty of Medicine, Bezmialem Vakıf University, Istanbul, Turkey.
Department of Medical Genetics, Istanbul Training and Research Hospital, Istanbul, Turkey.
Neuropediatrics. 2020 Dec;51(6):430-434. doi: 10.1055/s-0040-1710526. Epub 2020 May 5.
Biallelic mutations in the gene are responsible for early-onset progressive encephalopathy with brain atrophy and spasticity (PEBAS). To date, three different allelic variants have been reported. Next-generation sequencing allowed discovery of unique alternations in this gene with different phenotypes. We report two patients carrying TRAPPC12 variants, one previously reported and one unknown mutation, with severe neurodevelopmental delay and brain atrophy. Standard clinical examination and cranial imaging studies were performed in these two unrelated patients. In addition, whole-exome sequencing was performed, followed by Sanger sequencing for verification. The first patient, a 2-year-old boy, was found to be homozygous for the previously reported c.1880C > T (p.Ala627Val) mutation. He presented with a phenotype including severe progressive cortical atrophy, moderate cerebellar atrophy, epilepsy, and microcephaly, very similar to the previously reported cases. The second case, a 9-year-old boy, carried a novel homozygous c.679T > G (p.Phe227Val) variant and presented with mild cortical atrophy, severe cerebellar atrophy, and neither clinically manifest epilepsy nor microcephaly, which were previously considered typical findings in PEBAS with TRAPPC12 mutations. Our findings suggest that clinical and brain imaging findings might be more variable than previously anticipated; however, a larger number of observations would benefit for broader phenotypic spectrum.
该基因的双等位基因突变与早发性进行性脑病伴脑萎缩和痉挛（PEBAS）有关。迄今为止，已报道了三种不同的等位基因变体。二代测序技术使得能够发现该基因中具有不同表型的独特变异。我们报告了两名携带TRAPPC12变体的患者，其中一个是先前报道过的，另一个是未知突变，他们均有严重的神经发育迟缓及脑萎缩。对这两名无亲缘关系的患者进行了标准临床检查及头颅影像学检查。此外，还进行了全外显子组测序，随后采用桑格测序进行验证。第一名患者是一名2岁男孩，被发现为先前报道的c.1880C＞T（p.Ala627Val）突变的纯合子。他表现出的表型包括严重的进行性皮质萎缩、中度小脑萎缩、癫痫和小头畸形，与先前报道的病例非常相似。第二个病例是一名9岁男孩，携带一种新的纯合c.679T＞G（p.Phe227Val）变体，表现为轻度皮质萎缩、严重小脑萎缩，临床上既无癫痫表现也无小头畸形，而这些表现以前被认为是TRAPPC12突变所致PEBAS的典型表现。我们的研究结果表明，临床和脑影像学表现可能比先前预期的更具变异性；然而，更多的观察结果将有助于更广泛地表征其表型谱。
