PDF(Pubmed)
Abstract：
The case report by Mabry et al. (1970) of a family with four children with elevated tissue non-specific alkaline phosphatase, seizures and profound developmental disability, became the basis for phenotyping children with the features that became known as Mabry syndrome. Aside from improvements in the services available to patients and families, however, the diagnosis and treatment of this, and many other developmental disabilities, did not change significantly until the advent of massively parallel sequencing. As more patients with features of the Mabry syndrome were identified, exome and genome sequencing were used to identify the glycophosphatidylinositol (GPI) biosynthesis disorders (GPIBDs) as a group of congenital disorders of glycosylation (CDG). Biallelic variants of the phosphatidylinositol glycan (PIG) biosynthesis, type V (PIGV) gene identified in Mabry syndrome became evidence of the first in a phenotypic series that is numbered HPMRS1-6 in the order of discovery. HPMRS1 [MIM: 239300] is the phenotype resulting from inheritance of biallelic PIGV variants. Similarly, HPMRS2 (MIM 614749), HPMRS5 (MIM 616025) and HPMRS6 (MIM 616809) result from disruption of the PIGO, PIGW and PIGY genes expressed in the endoplasmic reticulum. By contrast, HPMRS3 (MIM 614207) and HPMRS4 (MIM 615716) result from disruption of post attachment to proteins PGAP2 (HPMRS3) and PGAP3 (HPMRS4). The GPI biosynthesis disorders (GPIBDs) are currently numbered GPIBD1-21. Working with Dr. Mabry, in 2020, we were able to use improved laboratory diagnostics to complete the molecular diagnosis of patients he had originally described in 1970. We identified biallelic variants of the PGAP2 gene in the first reported HPMRS patients. We discuss the longevity of the Mabry syndrome index patients in the context of the utility of pyridoxine treatment of seizures and evidence for putative glycolipid storage in patients with HPMRS3. From the perspective of the laboratory innovations made that enabled the identification of the HPMRS phenotype in Dr. Mabry\'s patients, the need for treatment innovations that will benefit patients and families affected by developmental disabilities is clear.
摘要：
Mabry等人的病例报告。（1970）一个有四个孩子的家庭，组织非特异性碱性磷酸酶升高，癫痫发作和严重的发育障碍，成为具有被称为Mabry综合征的特征的儿童表型的基础。除了改善为患者和家庭提供的服务外，然而,诊断和治疗，和许多其他发育障碍，在大规模平行测序出现之前没有显著变化。随着越来越多具有Mabry综合征特征的患者被发现，外显子组和基因组测序用于鉴定糖磷脂酰肌醇(GPI)生物合成障碍(GPIBDs)为一组先天性糖基化障碍(CDG).磷脂酰肌醇聚糖（PIG）生物合成的双等位基因变体，在Mabry综合征中鉴定出的V型（PIGV）基因成为表型系列中第一个的证据，该系列按发现顺序编号为HPMRS1-6。HPMRS1[MIM:239300]是由双等位基因PIGV变体的遗传产生的表型。同样，HPMRS2(MIM614749),HPMRS5（MIM616025）和HPMRS6（MIM616809）是由PIGO的破坏引起的，PIGW和PIGY基因在内质网中表达。相比之下,HPMRS3(MIM614207)和HPMRS4(MIM615716)由与蛋白质PGAP2(HPMRS3)和PGAP3(HPMRS4)的后附着的破坏产生。GPI生物合成障碍(GPIBDs)目前编号为GPIBD1-21。和Mabry医生一起工作,在2020年,我们能够使用改进的实验室诊断来完成他最初在1970年描述的患者的分子诊断.我们在首次报道的HPMRS患者中鉴定了PGAP2基因的双等位基因变体。我们在吡哆醇治疗癫痫发作的效用以及HPMRS3患者中推定的糖脂储存的证据的背景下，讨论了Mabry综合征指数患者的寿命。从实验室创新的角度来看，这些创新使Mabry博士的患者能够识别HPMRS表型，显然，有必要进行治疗创新，使受发育障碍影响的患者和家庭受益。
