FBN1基因突变引起的罕见的肢端骨骼发育不良变异的临床和遗传特征

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详细

论证。地球物理发育不良和肩关节发育不良是罕见的遗传性疾病，其特征是侏儒症和骨骼结构发育不良。在国外文献中，仅描述了少数由FBN1基因突变引起的血液学和肢端发育不良的病例，而在国内文献中我们还没有遇到对此类患者的临床和遗传特征的描述。

临床观察。描述了三名由FBN1基因中的三种错义突变引起的肢端发育不良的女性患者的临床和遗传特征。2例患者根据临床表现和X线检查资料诊断为肢端发育不良，1例患者诊断为血液物理发育不良。所有鉴定的突变都位于FBN1基因的外显子中，该基因编码第五结构域的氨基酸序列，与转化生长因子-β具有同源性。

讨论。对临床和遗传相关性的分析使得之前陈述的关于在具有c.5206T>C突变的患者中发生严重的血液物理发育不良表型的假设成为可能，导致在1736位用精氨酸替换半胱氨酸c.5284G>A (p.Gly1762Ser)。我们发现的先前未描述的置换c.5177G>A (p.Gly1726Asp) 以及该密码子中的另一个先前描述的突变，导致谷氨酰胺被缬氨酸取代，导致不那么明显的肩峰发育不良表型。

结论。根据对三名俄罗斯患者的检查结果以及对文献中描述的患者的临床和遗传特征的分析，发现导致肢端发育不良的FBN1基因突变，包括太阳物理和肢端发育不良发育不良，破坏类似于第五转化生长因子的氨基酸序列。1型原纤维蛋白的β结构域。最严重的临床表现见于突变导致多肽链第 1736位精氨酸被胱氨酸取代，从而导致转化生长因子-β信号通路功能中断的患者。

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作者简介

Tatyana Markova

Research Centre for Medical Genetics

编辑信件的主要联系方式.
Email: markova@med-gen.ru
ORCID iD: 0000-0002-2672-6294
SPIN 代码: 4707-9184

MD, PhD

俄罗斯联邦, Moskvorechye str., Moscow, 115522

Vladimir Kenis

H. Turner National Medical Research Centre for Children’s Orthopedics and Trauma Surgery

Email: kenis@mail.ru
ORCID iD: 0000-0002-7651-8485
SPIN 代码: 5597-8832
http://www.rosturner.ru/kl4.htm

MD, PhD, D.Sc.

俄罗斯联邦, Saint Petersburg

Evgenii Melchenko

H. Turner National Medical Research Centre for Children’s Orthopedics and Trauma Surgery

Email: emelchenko@gmail.com
ORCID iD: 0000-0003-1139-5573
SPIN 代码: 1552-8550

MD, PhD

俄罗斯联邦, Saint Petersburg

Tatyana Nagornova

Research Centre for Medical Genetics

Email: t.korotkaya90@gmail.com
ORCID iD: 0000-0003-4527-4518

MD, clinical geneticist

俄罗斯联邦, 1 Moskvorechye str., Moscow, 115522

Aysylu Murtazina

Research Centre for Medical Genetics

Email: aysylumurtazina@gmail.com
ORCID iD: 0000-0001-7023-7378
SPIN 代码: 9807-3783

MD, neurologist, doctor of functional diagnostics

俄罗斯联邦, 1 Moskvorechye str., Moscow, 115522

Elena Dadali

Research Centre for Medical Genetics

Email: genclinic@yandex.ru
ORCID iD: 0000-0001-5602-2805
SPIN 代码: 3747-7880

MD, PhD, D.Sc., Professor

俄罗斯联邦, Moskvorechye str., Moscow, 115522

参考

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1. JATS XML
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2. 图 1 先证者1，女孩，10个月：a - 患者的外观（不成比例的侏儒、四肢缩短、短肢畸形、手指屈曲挛缩、面部畸形）； b - 正面投影髋关节的X光片（颈骨干角增加，髋臼指数增加，股骨头骨化核发育不良）；c - 脊柱侧面投影的X射线 （胸椎椎体的卵形，不偏离轴线）

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3. 图 2 先证者2，女孩，3岁：a - 患者的外观（不成比例的侏儒症、短肢、短肢、手指间关节屈曲挛缩、面部表型特征）； b - 正面投影髋关节的X光片[颈骨干角增加（用白线标记）、髋臼指数（用黑线标记）、股骨近端骨骺内侧部分的 “珊瑚状”形状（用白色箭头标记）]；c - 手的-X光片[手指的短主指骨（用黑线勾勒出）、手指的短而宽的中间、发育不良的远端指骨（用白线勾勒出）、V底的内侧“切迹”（用黑色箭头标记）和外侧-II掌骨（用白色箭头标记出）]

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4. 图 3 先证者3，女孩，7岁：a - 患者的外貌（身材矮小，假性肌肉体质，四肢短，短肢，手关节挛缩，面部表型特征）； b - 正面投影髋关节的X光片[颈干角增加，髋臼指数增加，股骨头骨覆盖度降低（用黑色箭头标记），股骨近端骨骺形状改变，中间部分呈“珊瑚状”（用白色箭头标记）]；c - 脊柱侧面投影的c-X光片（椎体卵形，腰椎前凸轻度增加）； d - 正面投影的手部X光片[手指短而宽的指骨（用白色箭头标记），V掌骨底部的内侧“凹口”（用黑色箭头标记）]

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5. 图 4 患者中具有指示氨基酸替换的转化生长因子-β样结构域的蛋白质结构域（顶部）和氨基酸序列（底部）

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版权所有 © Markova T., Kenis V., Melchenko E., Nagornova T., Murtazina A., Dadali E., 2021

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