AbstractType 2 spinal muscular atrophy with lower extremity dominance (SMALED2) is caused by bicaudal D cargo adaptor 2 (BICD2) variants. However, the SMALED2 genotype and phenotype correlation have not been thoroughly characterized. We identified de novo heterozygous BICD2 missense variants in two fetuses with severe, prenatally diagnosed multiple arthrogryposis congenita.

摘要下肢优势型2型脊髓性肌萎缩症（SMALED2）是由双尾D货物适配器2（BICD2）变体引起的。然而，SMALED2基因型和表型的相关性尚未得到彻底表征。我们在两个胎儿中发现了从头杂合的BICD2错义变体，这些胎儿患有严重的，产前诊断的多发性先天性关节炎。

This report provides further insights into the genetics of this rare disease..

该报告进一步深入了解了这种罕见疾病的遗传学。。

Spinal muscular atrophy (SMA) with lower extremity dominance (SMALED), a rare SMA type, is characterized by musculature weakness and atrophy due to motor neuron dysfunction predominantly affecting the lower extremities and is caused by one of two autosomal dominantly inherited genes. SMALED2 (OMIM number 615290), a SMALED subtype, is caused by mutations in bicaudal D cargo adaptor 2 (BICD2) at 9q22.31.

具有下肢优势（SMALED）的脊髓性肌萎缩症（SMA）是一种罕见的SMA类型，其特征是肌肉组织无力和萎缩，这是由于运动神经元功能障碍主要影响下肢，并且是由两个常染色体显性遗传基因之一引起的。SMALED2（OMIM编号615290）是一种SMALED亚型，是由9q22.31的双尾D货物适配器2（BICD2）突变引起的。

Forty-five disease-causing BICD2 variants have been reported in the PubMed database. SMALED2A (OMIM number 615290) is a classical form with childhood-to-adulthood onset of muscular weakness and atrophy, predominantly affecting the lower extremities. SMALED2B (OMIM number 618291) is a more severe form with prenatal onset, congenital myopathy, and arthrogryposis1.

PubMed数据库中已报告了45种引起疾病的BICD2变体。SMALED2A（OMIM编号615290）是一种经典形式，从儿童期到成年期都会出现肌肉无力和萎缩，主要影响下肢。SMALED2B（OMIM编号618291）是一种更严重的形式，具有产前发作，先天性肌病和关节软化症1。

The correlations between the genotypes and phenotypes of SMALED2 remain unclear. We encountered two patients with BICD2 de novo variants associated with severe multiple arthrogryposis congenita. Here, we present genetic variant information and the phenotypic prenatal course of the disease.In Case 1, a 24-year-old nulliparous pregnant woman without significant medical or family history was referred to our hospital for a fetus with multiple fetal arthrogryposis at 17+6 weeks of gestation (Fig.

SMALED2的基因型和表型之间的相关性尚不清楚。我们遇到了两名患有BICD2从头变异并伴有严重多发性先天性关节炎的患者。在这里，我们介绍遗传变异信息和疾病的表型产前过程。在病例1中，一名24岁的未产妇没有明显的病史或家族史，在妊娠17+6周时被转诊到我们医院接受多胎关节置换的胎儿（图）。

1a). Fetal ultrasonographic findings revealed flexed fetal wrist and elbow joints, adducted and flexed hip joints, extended knee and foot joints with talipes equinovarus, and no fetal movement (Fig. 1b and c). Despite thorough counseling, she chose to terminate the pregnancy at 19+6 weeks of gestation.Fig.

1a）。胎儿超声检查结果显示胎儿腕关节和肘关节弯曲，髋关节内收和弯曲，膝关节和足关节延长，伴有马蹄内翻足，无胎动（图1b和c）。尽管进行了彻底的咨询，她还是选择在妊娠19+6周时终止妊娠。图。

1: Pedigree of Cases 1 and 2 and prenatal and postnatal images of affected fetuses.a Pedigree of Case 1. b, c Prenatal ultrasonographic images of Case 1 at 18+2 weeks of gestation. d Pedigree of Case 2. e, f Prenatal ultraso.

1： 病例1和2的血统书以及受影响胎儿的产前和产后图像。病例1的血统书。b、 c妊娠18+2周时病例1的产前超声图像。d病例2的血统书。e、 f产前超声波。

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Download referencesAcknowledgementsThe authors are grateful to the patients and their family members for permission to use their clinical information in this article. This study was partly supported by a research grant from JSPS KAKENHI (grant numbers: JP 23K15822 and 23K07256).Author informationAuthors and AffiliationsDepartment of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, JapanLayla Masuda, Akihiro Hasegawa, Michihiro Yamamura, Yuki Ito, Osamu Samura & Aikou OkamotoDepartment of Maternal–Fetal Biology, National Research Institute for Child Health and Development, Tokyo, JapanHiromi Kamura, Kosuke Taniguchi & Kenichiro HataCenter for Clinical Genetics, National Center for Child Health and Development, Tokyo, JapanFuyuki HasegawaDepartment of Human Molecular Genetics, Gunma University Graduate School of Medicine, Gunma, JapanKosuke Taniguchi & Kenichiro HataAuthorsLayla MasudaView author publicationsYou can also search for this author in.

下载参考文献致谢作者感谢患者及其家属允许在本文中使用他们的临床信息。这项研究部分得到了JSPS KAKENHI的研究资助（资助号：JP 23K15822和23K07256）。作者信息作者和所属机构东京经济大学医学院妇产科，日本来拉Masuda，长谷川昭弘，山村弥弘，伊藤由纪，大坂三村和爱口冈本国立儿童健康与发展研究所母胎生物学系，东京，日本野村，谷口Kosuke&HataCenter for Clinical Genetics，National Center for Child Health and Development，Tokyo，JapanFuyuki HasegawaDepartment of Human Molecular Genetics，群马大学医学研究生院，群马，JapanKosuke Taniguchi＆Kenichiro HataAuthorsLayla MasudaView作者出版物您也可以在中搜索这位作者。

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Reprints and permissionsAbout this articleCite this articleMasuda, L., Hasegawa, A., Kamura, H. et al. Missense BICD2 variants in fetuses with congenital arthrogryposis and pterygia.

转载和许可本文引用本文Masuda，L.，Hasegawa，A.，Kamura，H。等人。先天性关节炎和翼状胬肉胎儿的错义BICD2变异。

Hum Genome Var 11, 32 (2024). https://doi.org/10.1038/s41439-024-00290-zDownload citationReceived: 24 April 2024Revised: 17 July 2024Accepted: 25 July 2024Published: 26 August 2024DOI: https://doi.org/10.1038/s41439-024-00290-zShare this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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