Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Am J Med Genet A. 2023 Sep;191(9):2446-2450. doi: 10.1002/ajmg.a.63310. Epub 2023 Jun 20.
Combined oxidative phosphorylation deficiency type 53 (COXPD53) is an autosomal recessive neurodevelopmental disorder (NDD) caused by homozygous variants in the gene C2orf69. Here, we report a novel frameshift variant c.187_191dupGCCGA, p.D64Efs56 identified in an individual with clinical presentation of COXPD53 with developmental regression and autistic features. The variant c.187_191dupGCCGA, p.D64Efs56 represents the most N-terminal part of C2orf69. Notable clinical features of COXPD53of the proband include developmental delay, developmental regression, seizures, microcephaly, and hypertonia. Structural brain defects of cerebral atrophy, cerebellar atrophy, hypomyelination, and thin corpus callosum were also observed. While we observe strong phenotypic overlap among affected individuals with C2orf69 variants, developmental regression and autistic features have not been previously described in individuals with COXPD53. Together, this case expands the genetic and clinical phenotypic spectrum of C2orf69-associated COXPD53.
联合氧化磷酸化缺陷 53 型（COXPD53）是一种常染色体隐性神经发育障碍（NDD），由 C2orf69 基因中的纯合变异引起。在这里，我们报道了一名 COXPD53 患者的临床表型为发育倒退和自闭症特征的新型移码变异 c.187_191dupGCCGA，p.D64Efs56。该变异 c.187_191dupGCCGA，p.D64Efs56 代表 C2orf69 的最 N 端部分。先证者 COXPD53 的显著临床特征包括发育迟缓、发育倒退、癫痫发作、小头畸形和高张力。还观察到结构性脑缺陷，包括脑萎缩、小脑萎缩、少突胶质细胞发育不良和薄胼胝体。虽然我们观察到 C2orf69 变异患者的表型重叠很强，但 COXPD53 患者以前没有描述过发育倒退和自闭症特征。总之，该病例扩展了 C2orf69 相关 COXPD53 的遗传和临床表型谱。
