一种纯合的层粘连蛋白B受体变体，导致Pelger Huët异常，但没有骨骼发育不良
A homozygous lamin B receptor variant resulting in Pelger-Huët anomaly without skeletal dysplasia.
摘要(中文译文)
层粘连蛋白B受体（lamin B receptor，LBR）是一种内核膜蛋白，具有影响中性粒细胞核分叶的结构功能，以及作为甾醇还原酶的酶学功能。杂合变异导致核分叶减少（Pelger-Huët异常），而纯合致病性变异则导致一系列系统性畸形，甚至严重的骨骼畸形和产前死亡。早在1981年，已有报道一例纯合Pelger-Huët先证者，其表现为中性粒细胞核呈卵圆形，但无特殊临床症状。随后研究表明LBR量减少，可能由调控性变异所致。我们现已重新分析该先证者的DNA，证实存在纯合错义变异（NM_002296.4）：c.1445T > G；p.V482G。然而，进一步的分子检测未发现任何调控性变异。对该错义变异进行了进一步研究：其影响一个进化上高度保守的氨基酸，该氨基酸与内核膜直接接触，但对LBR甾醇还原酶活性无直接影响。迄今为止，尚未在任何研究中检测到纯合缬氨酸至甘氨酸的替换。因此，我们得出结论：该变异对LBR的结构功能具有显著影响，但对其酶学功能无临床相关影响。
Abstract
The lamin B receptor (LBR) is an inner nuclear membrane protein with a structural function affecting nuclear segmentation in neutrophils and an enzymatic function as a sterol reductase. Heterozygous variants cause nuclear hyposegmentation (Pelger-Huët anomaly), while homozygous pathogenic variants cause a spectrum of systemic malformations up to severe skeletal deformities and prenatal death. Already in 1981, a homozygous Pelger-Huët proband with ovoid neutrophil nuclei but without special clinical symptoms has been reported. Later it was shown that the amount of LBR was reduced, perhaps due to a regulatory variant. We have now re-analyzed the proband´s DNA and confirmed the existence of a homozygous missense variant (NM_002296.4): c.1445T > G; p.V482G. However, further molecular testing did not reveal any regulatory variant. The missense variant was further investigated: It affects an evolutionary highly conserved amino acid, which is in direct contact with the inner nuclear membrane, but has no direct influence on the LBR sterol reductase activity. A homozygous valine to glycine substitution has not been detected in any study so far. Therefore, we conclude that this variant has a significant effect on the structural function of LBR but no clinically relevant effect on its enzymatic function.
如何引用
AMA
Katrin Hoffmann, Amparo Vayá, José M Ricart Vayá, Oliver Küchler, Axel Schmidt, Nicolai von Kügelgen, et al. A homozygous lamin B receptor variant resulting in Pelger-Huët anomaly without skeletal dysplasia.. Nucleus (Austin, Tex.). 2026; doi:10.1080/19491034.2026.2720062.
APA
Katrin Hoffmann, Amparo Vayá, José M Ricart Vayá, Oliver Küchler, Axel Schmidt, Nicolai von Kügelgen, et al (2026). A homozygous lamin B receptor variant resulting in Pelger-Huët anomaly without skeletal dysplasia.. Nucleus (Austin, Tex.). https://doi.org/10.1080/19491034.2026.2720062
GB/T 7714
Katrin Hoffmann, Amparo Vayá, José M Ricart Vayá, Oliver Küchler, Axel Schmidt, Nicolai von Kügelgen, et al. A homozygous lamin B receptor variant resulting in Pelger-Huët anomaly without skeletal dysplasia.[J]. Nucleus (Austin, Tex.), 2026 doi:10.1080/19491034.2026.2720062.
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