Balasubramanian Meena, Johnson Diana S
Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, UK; Highly Specialised Service for Severe, Complex and Atypical OI Service, Sheffield Children's NHS Foundation Trust, Sheffield, UK; Academic Unit of Child Health, University of Sheffield, UK.
Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, UK.
Eur J Med Genet. 2019 Feb;62(2):109-114. doi: 10.1016/j.ejmg.2018.06.011. Epub 2018 Jun 14.
Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases due to impaired lipid and protein glycosylation. It comprises a characteristic high frequency of intellectual disability (ID) and a wide range of clinical phenotypes.
To identify the underlying diagnosis in two families each with two siblings with variable level of ID through trio whole exome sequencing.
Both the families were recruited to the Deciphering Developmental Disorders (DDD) study to identify the aetiology for their ID. Further work-up included isoelectric focusing (IEF) of serum transferrin done to add evidence to the molecular diagnosis.
These patients were found to have three novel variants in MAN1B1 inherited from their healthy parents. Serum transferrin IEF showed a type 2 pattern.
MAN1B1 variants were initially described in association with non-syndromic ID; subsequent literature suggested that variants in MAN1B1 resulted in a CDG-type II syndrome. However, there remains a paucity of literature on detailed clinical phenotyping and it still remains a rare form of CDG. The present patients showed the phenotype previously reported in MAN1B1-CDG: a characteristic facial dysmorphism, hypotonia, truncal obesity and in some, behavioural problems.
In unexplained ID, serum transferrin should be included in the first-line screening. With advances in genomic medicine, it is important to diagnose CDG as this has implications for management and recurrence risk counselling.
先天性糖基化障碍（CDG）是一组由于脂质和蛋白质糖基化受损导致的罕见代谢性疾病。其特征是智力残疾（ID）的高发病率以及广泛的临床表型。
通过三联体全外显子测序确定两个家庭中各有两名ID程度不同的兄弟姐妹的潜在诊断。
这两个家庭均被纳入发育障碍解读（DDD）研究以确定其ID的病因。进一步的检查包括对血清转铁蛋白进行等电聚焦（IEF），以补充分子诊断的证据。
这些患者被发现从其健康父母那里遗传了MAN1B1基因的三个新变异。血清转铁蛋白IEF显示为2型模式。
MAN1B1变异最初被描述与非综合征性ID相关；随后的文献表明MAN1B1变异导致II型CDG综合征。然而，关于详细临床表型分析的文献仍然很少，它仍然是一种罕见的CDG形式。目前的患者表现出先前在MAN1B1 - CDG中报道的表型：特征性面部畸形、肌张力低下、躯干肥胖，部分患者还有行为问题。
在不明原因的ID中，血清转铁蛋白应纳入一线筛查。随着基因组医学的发展，诊断CDG很重要，因为这对管理和复发风险咨询有影响。
