Medical Genetics Unit, P.O. Gaetano Rummo, A.O.R.N. San Pio, Via dell'Angelo, 1, 82100 Benevento, Italy.
Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138 Naples, Italy.
Genes (Basel). 2023 Jul 14;14(7):1444. doi: 10.3390/genes14071444.
Glycosylphosphatidylinositol biosynthesis defect 15 is a rare autosomal recessive disorder due to biallelic loss of function of GPAA1. At the moment, less than twenty patients have been reported, usually compound heterozygous for GPAA1 variants. The main clinical features are intellectual disability, hypotonia, seizures, and cerebellar atrophy. We describe a 4-year-old male with a novel, homozygous variant. The patient presents with typical features, such as developmental delay, hypotonia, seizures, and atypical features, such as macrocephaly, preauricular, and cheek appendages. When he was 15 months, the cerebellum was normal. When he was 33 months old, after the molecular diagnosis, magnetic resonance imaging was repeated, showing cerebellar atrophy. This case extends the clinical spectrum of the GPAA1-related disorder and helps to delineate phenotypic differences with defects of other subunits of the transamidase complex.
糖基磷脂酰肌醇生物合成缺陷 15 是一种罕见的常染色体隐性遗传病，由 GPAA1 的双等位基因功能丧失引起。目前，不到二十名患者被报道，通常是 GPAA1 变异的复合杂合子。主要临床特征为智力障碍、低张力、癫痫发作和小脑萎缩。我们描述了一名 4 岁男性的新型纯合变异病例。该患者表现出典型特征，如发育迟缓、低张力、癫痫发作，以及非典型特征，如大头畸形、耳前和颊部附属物。他 15 个月大时，小脑正常。他 33 个月大时，进行了分子诊断后，重复了磁共振成像，显示小脑萎缩。该病例扩展了 GPAA1 相关疾病的临床谱，并有助于描绘与转酰胺酶复合物其他亚基缺陷的表型差异。
