UMR 8576, Univ. Lille, CNRS, UGSF - Unité de Glycobiologie Structurale Et Fonctionnelle, 59000, Lille, France.
Centre de Biologie Et Pathologie, Lille Medical Center, University of Lille, UAM de glycopathologies, 59000, Lille, France.
Ital J Pediatr. 2022 Oct 11;48(1):178. doi: 10.1186/s13052-022-01355-x.
Congenital Disorders of Glycosylation (CDG) are a large group of inborn errors of metabolism with more than 140 different CDG types reported to date (1). The first characterized, PMM2-CDG, with an autosomal recessive transmission, is also the most frequent. The PMM2 gene encodes a phosphomannomutase. Here, a novel genetic variation causing PMM2-CDG is reported. CASE PRESENTATION: We report the case of a French child, from healthy and unrelated parents, presenting congenital ataxia with hypotonia, hyperlaxity, inverted nipples, as well as altered coagulation parameters and liver function. Transferrin isoelectrofocusing revealed a typical type I CDG profile. Direct Sanger sequencing and quantitative PCR of PMM2 revealed a unique and novel genotype. On one allele, the patient was heterozygote with a known missense variant NM_000303.3(PMM2):c.323C > T, p.Ala108Val in exon 4. On the second allele, whole genome sequencing (WGS) indicated the presence of a novel heterozygous 70 kb deletion.
We report in the present paper the largest known heterozygous deletion of a PMM2 gene. The observation reveals the impact of a precise diagnostic on genetic counselling: by using WGS, an erroneous conclusion of homozygosity in the case of a relatively rare variant could be avoided, and an index patient with healthy and unrelated parents correctly identified.
先天性糖基化障碍（CDG）是一大类先天性代谢缺陷，迄今为止已报道超过 140 种不同的 CDG 类型（1）。第一个被表征的常染色体隐性遗传的 PMM2-CDG 也是最常见的。PMM2 基因编码磷酸甘露糖变位酶。在此，报告了一种导致 PMM2-CDG 的新型遗传变异。
我们报告了一名来自健康无亲缘关系父母的法国儿童的病例，表现为先天性共济失调伴低张力、高弛缓、乳头内陷，以及凝血功能和肝功能异常。转铁蛋白等电聚焦显示典型的 I 型 CDG 图谱。PMM2 的直接 Sanger 测序和定量 PCR 显示出一种独特的新型基因型。在一个等位基因上，患者为杂合子，携带已知的错义变异 NM_000303.3(PMM2):c.323C>T，p.Ala108Val，位于外显子 4。在第二个等位基因上，全基因组测序（WGS）显示存在一种新型杂合 70kb 缺失。
本文报告了已知最大的 PMM2 基因杂合缺失。该观察结果揭示了精确诊断对遗传咨询的影响：通过使用 WGS，可以避免在罕见变异的情况下错误地得出纯合子的结论，并正确识别出健康无亲缘关系父母的索引患者。
