bims-meglyc Biomed News
on Metabolic disorders affecting glycosylation
Issue of 2023–08–20
two papers selected by
Silvia Radenkovic, Frontiers in Congenital Disorders of Glycosylation Consortium
  1. Congenital diaphragmatic hernia in siblings with PIGA-related congenital disorder of glycosylation.
  2. Expanding the genetic and clinical spectrum of SORD-related peripheral neuropathy by reporting a novel variant c.210T>G and evidence of subclinical muscle involvement.
  1. Am J Med Genet A. 2023 Aug 17.
    Congenital diaphragmatic hernia in siblings with PIGA-related congenital disorder of glycosylation.
    Molly M Crenshaw, Lauren Thompson, Daniel G Piqué, Kestutis Micke, Margarita Saenz, Peter R Baker.
      There are over 150 proteins involved in glycosylphosphatidylinositol (GPI)-anchored protein biosynthesis, a class within the larger category of congenital disorders of glycosylation (CDG). Pathogenic variants identified in phosphatidylinositol glycan class A protein (PIGA) are associated with X-linked PIGA-CDG, a GPI-anchor defect. The disease has primarily been characterized by hypotonia, epilepsy, and global developmental delay; however, only 89 known cases are reported, so the phenotypic spectrum has likely not yet been fully delineated. Congenital diaphragmatic hernia (CDH) has been reported in patients with various GPI-anchor related defects but has only been described in one prior individual with PIGA-CDG. Here, we describe the second and third reported cases of CDH in two brothers with PIGA-CDG caused by a pathogenic missense variant in PIGA: c.355C > T, p.R119W. Chromosomal microarray and whole exome sequencing did not reveal another plausible explanation for the CDH. We relate our patients' clinical features to the single previously reported individual with CDH and PIGA-CDG. We then compare this case series with the subset of individuals with CDH and other GPI-anchor defects. These findings suggest that CDH should be considered in the phenotypic disease spectrum of PIGA-CDG.
    Keywords:  PIGA; congenital diaphragmatic hernia; congenital disorder of glycosylation
    DOI:  https://doi.org/10.1002/ajmg.a.63373
  2. J Peripher Nerv Syst. 2023 Aug 16.
    Expanding the genetic and clinical spectrum of SORD-related peripheral neuropathy by reporting a novel variant c.210T>G and evidence of subclinical muscle involvement.
    Lu Li, Yongzhi Xie, Sen Zeng, Xiaobo Li, Zhiqiang Lin, Shunxiang Huang, Huadong Zhao, Wanqian Cao, Lei Liu, Jun Liu, Pengfei Rong, Ruxu Zhang.
       BACKGROUND AND AIMS: Biallelic variants in the sorbitol dehydrogenase (SORD) gene have been identified as the genetic cause of autosomal recessive (AR) peripheral neuropathy (PN) manifesting as Charcot-Marie-Tooth disease type 2 (CMT2) or distal hereditary motor neuropathy (dHMN). We aim to observe the genetic and clinical spectrum of a cohort of patients with SORD-related PN (SORD-PN).
    METHODS: A total of 107 patients with AR or sporadic CMT2/dHMN underwent molecular diagnosis by whole-exome sequencing and subsequent Sanger sequencing validation. Available phenotypic data for SORD-PN were collected and analyzed.
    RESULTS: Eleven (10.28%) of 107 patients were identified as SORD-PN, including 4 with CMT2 and 7 with dHMN. The SORD variant c.210T>G;p.His70Gln in F-d3 was firstly reported and subsequent analysis showed that it resulted in loss of SORD enzyme function. Evidence of subclinical muscle involvement was frequently detected in patients with SORD-PN, including mildly to moderately elevated serum creatine kinase (CK) levels in 10 patients, myogenic electrophysiological changes in 1 patient, and muscle edema in 5 patients undergoing lower extremity MRI. Fasting serum sorbitol level was 88-fold higher in SORD-PN patients (9.69±1.07mg/l) than in healthy heterozygous subjects (0.11±0.01mg/l) and 138-fold higher than in healthy controls (0.07±0.02mg/l).
    INTERPRETATION: The novel SORD variant c.210T>G;p.His70Gln and evidence of subclinical muscle involvement were identified, which expanded the genetic and clinical spectrum of SORD-PN. Subclinical muscle involvement might be a common but easily overlooked clinical feature. The serum CK and fasting serum sorbitol levels were expected to be sensitive biomarkers confirmed by follow-up cohort study. This article is protected by copyright. All rights reserved.
    Keywords:  Charcot-Marie-Tooth disease type 2; SORD; distal hereditary motor neuropathy; novel variant; related peripheral neuropathy; subclinical muscle involvement
    DOI:  https://doi.org/10.1111/jns.12591
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