PDF(Sci-hub)
Abstract：
BACKGROUND: Phosphomannomutase 2 deficiency (PMM2-CDG) affects glycosylation pathways such as the N-glycosylation pathway, resulting in loss of function of multiple proteins. This disorder causes multisystem involvement with a high variability among patients. PMM2-CDG is an autosomal recessive disorder, which can be caused by inheriting two pathogenic variants, de novo mutations or uniparental disomy.
METHODS: Our patient presented with multisystem symptoms at an early age including developmental delay, ataxia, and seizures. No diagnosis was obtained till the age of 31 years, when genetic testing was reinitiated. The patient was diagnosed with a complete maternal mixed hetero/isodisomy of chromosome 16, with a homozygous pathogenic PMM2 variant (p.Phe119Leu) causing PMM2-CDG.A literature review revealed eight cases of uniparental disomy as an underlying cause of CDG, four of which are PMM2-CDG.
CONCLUSIONS: Since the incidence of homozygosity for PMM2 variants is rare, we suggest further investigations for every homozygous PMM2-CDG patient where the segregation does not fit. These investigations include testing for UPD or a deletion in one of the two alleles, as this will have an impact on recurrence risk in genetic counseling.
METHODS: Our patient presented with multisystem symptoms at an early age including developmental delay, ataxia, and seizures. No diagnosis was obtained till the age of 31 years, when genetic testing was reinitiated. The patient was diagnosed with a complete maternal mixed hetero/isodisomy of chromosome 16, with a homozygous pathogenic PMM2 variant (p.Phe119Leu) causing PMM2-CDG.A literature review revealed eight cases of uniparental disomy as an underlying cause of CDG, four of which are PMM2-CDG.
CONCLUSIONS: Since the incidence of homozygosity for PMM2 variants is rare, we suggest further investigations for every homozygous PMM2-CDG patient where the segregation does not fit. These investigations include testing for UPD or a deletion in one of the two alleles, as this will have an impact on recurrence risk in genetic counseling.
摘要：
背景：磷酸甘露聚糖变位酶2缺乏症（PMM2-CDG）影响糖基化途径，例如N-糖基化途径，导致多种蛋白质的功能丧失。这种疾病导致多系统受累，患者之间存在高度变异性。PMM2-CDG是一种常染色体隐性遗传疾病，这可能是由遗传两种致病变种引起的，从头突变或单亲二分法。
方法：我们的患者在早期出现多系统症状，包括发育迟缓，共济失调,和癫痫发作。直到31岁才得到诊断，当基因检测重新启动时。该患者被诊断为16号染色体的完全母体混合异型/等分体，具有纯合致病性PMM2变体（p。Phe119Leu）引起PMM2-CDG。文献综述显示，八例单亲二分法是CDG的根本原因，其中四个是PMM2-CDG。
结论：由于PMM2变体纯合性的发生率很少，我们建议对每个分离不符合的纯合子PMM2-CDG患者进行进一步调查.这些调查包括检测UPD或两个等位基因之一的缺失，因为这将对遗传咨询中的复发风险产生影响。
方法：我们的患者在早期出现多系统症状，包括发育迟缓，共济失调,和癫痫发作。直到31岁才得到诊断，当基因检测重新启动时。该患者被诊断为16号染色体的完全母体混合异型/等分体，具有纯合致病性PMM2变体（p。Phe119Leu）引起PMM2-CDG。文献综述显示，八例单亲二分法是CDG的根本原因，其中四个是PMM2-CDG。
结论：由于PMM2变体纯合性的发生率很少，我们建议对每个分离不符合的纯合子PMM2-CDG患者进行进一步调查.这些调查包括检测UPD或两个等位基因之一的缺失，因为这将对遗传咨询中的复发风险产生影响。
