Clinical, genetic, and structural characterization of a novel TUBB4B tubulinopathy.
Clinical, genetic, and structural characterization of a novel TUBB4B tubulinopathy.
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新型TUBB4B肾小管病的临床，遗传和结构表征。
DOI：
10.1016/j.ymgmr.2023.100990
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发表时间：
2023-09
影响因子：
1.9
通讯作者：
Malicdan, May Christine V.
中科院分区：
文献类型：
--
作者：
McFadden, Jason R.;Tolete, Christina Deanne P.;Huang, Yan;Macnamara, Ellen;Sept, David;Nesterova, Galina;Gahl, William A.;Sackett, Dan L.;Malicdan, May Christine V.
微管是⍺/β-微管蛋白杂二聚体的细胞骨架聚合物，在广泛的细胞过程中是必不可少的。微管编码基因的致病变异(例如，编码β-4B微管蛋白同型的TUBB4B)导致了一系列脑部畸形，统称为“微管病变”。TUBB4B相关性小管病变的表型表现为Leber先天性黑素性早发性耳聋(LCAEOD)，这是一种常染色体显性遗传综合征，特征是光感受器和耳蜗细胞丢失；所有已知的患者都有氨基酸R391的致病变异。我们报告了一例16岁女性的临床和分子遗传学结果，该女性在TUBB4B，c.32A和GG(p.Gln11Arg；Q11R)外显子1有新的错义变异。除了听力损失和无视网膜异常的远视外，我们的先证者还表现出两种遗传原因不明的表型，即肾小管性范可尼综合征(FS)和低磷血症性软骨病(HR)。Q11R变异体扩展了早期感觉性听力损失的遗传基础；它对微管结构的影响进行了描述。提出了FS和软骨病的机制解释，涉及到微管介导的转运蛋白进入和离开肾近端小管细胞的顶膜。
Microtubules are cytoskeletal polymers of ⍺/β-tubulin heterodimers essential for a wide range of cellular processes. Pathogenic variations in microtubule-encoding genes (e.g., TUBB4B, which encodes the β-4B tubulin isotype) are responsible for a wide spectrum of cerebral malformations, collectively referred to as “tubulinopathies.” The phenotypic manifestation of TUBB4B-associated tubulinopathy is Leber congenital amaurosis with early-onset deafness (LCAEOD), an autosomal dominant syndrome characterized by photoreceptor and cochlear cell loss; all known patients have pathogenic variations in amino acid R391. We present the clinical and molecular genetics findings of a 16-year-old female with a de novo missense variant in exon 1 of TUBB4B, c.32 A > G (p.Gln11Arg; Q11R). In addition to hearing loss and hyperopia without retinal abnormalities, our proband presented with two phenotypes of unknown genetic etiology, i.e., renal tubular Fanconi Syndrome (FS) and hypophosphatemic rickets (HR). The Q11R variant expands the genetic basis of early sensory hearing loss; its consequences with respect to microtubule structure are described. A mechanistic explanation for the FS and rickets, involving microtubule-mediated translocation of transporter proteins to and from the apical membrane of renal proximal tubular cells, is proposed.
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影响因子：
9.8
作者：
Luscan, Romain;Mechaussier, Sabrina;Perrault, Isabelle
通讯作者：
Perrault, Isabelle
影响因子：
9.8
作者：
Chao, Hsiao-Tuan;Davids, Mariska;Malicdan, May Christine V.
通讯作者：
Malicdan, May Christine V.
DOI：
10.1007/s00590-014-1496-y
发表时间：
2015-02-01
期刊：
European journal of orthopaedic surgery & traumatology : orthopedie traumatologie
影响因子：
--
作者：
Pavone, Vito;Testa, Gianluca;Sessa, Giuseppe
通讯作者：
Sessa, Giuseppe
影响因子：
3.8
作者：
Markello, Thomas C.;Han, Ted;Carlson-Donohoe, Hannah;Ahaghotu, Chidi;Harper, Ursula;Jones, MaryPat;Chandrasekharappa, Settara;Anikster, Yair;Adams, David R.;Gahl, William A.;Boerkoel, Cornelius F.
通讯作者：
Boerkoel, Cornelius F.
影响因子：
8.8
作者：
Gahl, William A.;Markello, Thomas C.;Toro, Camilo;Fajardo, Karin Fuentes;Sincan, Murat;Gill, Fred;Carlson-Donohoe, Hannah;Gropman, Andrea;Pierson, Tyler Mark;Golas, Gretchen;Wolfe, Lynne;Groden, Catherine;Godfrey, Rena;Nehrebecky, Michele;Wahl, Colleen;Landis, Dennis M. D.;Yang, Sandra;Madeo, Anne;Mullikin, James C.;Boerkoel, Cornelius F.;Tifft, Cynthia J.;Adams, David
通讯作者：
Adams, David