Zhao Shichao, Lian Ruofei, Jin Liang, Li Mengchun, Jia Tianming, Xu Falin, Du Kaixian, Wang Lijun, Guo Qiliang, Dong Yan
Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Henan Key Laboratory of Child Brain Injury, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Epilepsia Open. 2024 Feb;9(1):250-257. doi: 10.1002/epi4.12862. Epub 2023 Dec 8.
Defects in RARS2 cause cerebellopontine hypoplasia type 6 (pontocerebellar hypoplasia type 6, PCH6, OMIM: #611523), a rare autosomal recessive inherited mitochondrial disease. Here, we report two male patients and their respective family histories.
We describe the clinical presentation and magnetic resonance imaging (MRI) findings of these patients. Whole-exome sequencing was used to identify the genetic mutations.
One patient showed hypoglycemia, high lactic acid levels (fluctuating from 6.7 to 14.1 mmol/L), and frequent seizures after birth, with progressive atrophy of the cerebrum, cerebellum, and pons. The other patient presented with early infantile developmental and epileptic encephalopathies (EIDEEs) with an initial developmental delay followed by infantile epileptic spasm syndrome (IESS) at 5 months old, with no imaging changes. Whole-exome sequencing identified compound heterozygous RARS2 variants c.25A>G (p.I9V) with c.1261C>T (p.Q421*) and c.1A>G (p.M1V) with c.122A>G (p.D41G) in these two patients. Of these loci, c.1261C>T and c.122A>G have not been previously reported.
Our findings have expanded the RARS2 gene variant spectrum and present EIDEEs and IESS as phenotypes which deepened the association between PCH6 and RARS2.
Defects in RARS2 cause cerebellopontine hypoplasia type 6, a rare autosomal recessive inherited mitochondrial disease. Two patients with RARS2 variants were reported in this article. One patient showed hypoglycemia, high lactic acid levels, and frequent seizures after birth, with progressive atrophy of the cerebrum, cerebellum, and Page 3 of 21 Epilepsia OpenFor Review Only pons. The other patient presented with an initial developmental delay followed by refractory epilepsy at 5 months old, with no imaging changes. Our findings deepened the association between PCH6 and RARS2.
RARS2基因缺陷会导致6型脑桥小脑发育不全（脑桥小脑发育不全6型，PCH6，OMIM：#611523），这是一种罕见的常染色体隐性遗传线粒体疾病。在此，我们报告两名男性患者及其各自的家族病史。
我们描述了这些患者的临床表现和磁共振成像（MRI）结果。采用全外显子组测序来识别基因突变。
一名患者出生后出现低血糖、高乳酸水平（波动于6.7至14.1 mmol/L）和频繁癫痫发作，伴有大脑、小脑和脑桥进行性萎缩。另一名患者表现为早期婴儿发育性和癫痫性脑病（EIDEEs），最初发育迟缓，5个月大时出现婴儿癫痫痉挛综合征（IESS），影像学无变化。全外显子组测序在这两名患者中鉴定出复合杂合RARS2变异，分别为c.25A>G（p.I9V）与c.1261C>T（p.Q421*）以及c.1A>G（p.M1V）与c.122A>G（p.D41G）。在这些位点中，c.1261C>T和c.122A>G此前未见报道。
我们的发现扩展了RARS2基因变异谱，并将EIDEEs和IESS呈现为表型，加深了PCH6与RARS2之间的关联。
RARS2基因缺陷会导致6型脑桥小脑发育不全，这是一种罕见的常染色体隐性遗传线粒体疾病。本文报告了两名携带RARS2变异的患者。一名患者出生后出现低血糖、高乳酸水平和频繁癫痫发作，伴有大脑、小脑和脑桥进行性萎缩。另一名患者最初发育迟缓，5个月大时出现难治性癫痫，影像学无变化。我们的发现加深了PCH6与RARS2之间的关联。
