Final Exon Frameshift Biallelic PTPN23 Variants Are Associated with Microcephalic Complex Hereditary Spastic Paraplegia.
Final Exon Frameshift Biallelic PTPN23 Variants Are Associated with Microcephalic Complex Hereditary Spastic Paraplegia.
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DOI：
10.3390/brainsci11050614
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发表时间：
2021-05-11
期刊：
影响因子：
3.3
通讯作者：
Crosby AH
中科院分区：
文献类型：
--
作者：
Khalaf-Nazzal R;Fasham J;Ubeyratna N;Evans DJ;Leslie JS;Warner TT;Al-Hijawi F;Alshaer S;Baker W;Turnpenny PD;Baple EL;Crosby AH
遗传性痉挛性截瘫（HSP）是一组临床上异质的遗传疾病群体，当时是“纯净”的遗传疾病，当渐进的下肢痉挛和无力的基本特征孤立而“复杂”时，当我们与其他临床迹象相关时，我们确定了一个人量化的23（均量均匀的代码）。扩展的巴勒斯坦家庭与ptpn23的常染色体隐性复合物HSP相关。与致病基因有关的结果这种变体确定了许多先前提出的候选PTPN23的变化可能是良性的，并揭示了病原性偏见的PTPN23改变会导致多种临床谱系，这些临床频谱包含与微型畸形相关的复杂性HSP，这可能会涉及更严重的神经性疾病，这可能会涉及智力障碍。 Els全球。
The hereditary spastic paraplegias (HSPs) are a large clinically heterogeneous group of genetic disorders classified as ‘pure’ when the cardinal feature of progressive lower limb spasticity and weakness occurs in isolation and ‘complex’ when associated with other clinical signs. Here, we identify a homozygous frameshift alteration occurring in the last coding exon of the protein tyrosine phosphatase type 23 (PTPN23) gene in an extended Palestinian family associated with autosomal recessive complex HSP. PTPN23 encodes a catalytically inert non-receptor protein tyrosine phosphatase that has been proposed to interact with the endosomal sorting complex required for transport (ESCRT) complex, involved in the sorting of ubiquitinated cargos for fusion with lysosomes. In view of our data, we reviewed previously published candidate pathogenic PTPN23 variants to clarify clinical outcomes associated with pathogenic gene variants. This determined that a number of previously proposed candidate PTPN23 alterations are likely benign and revealed that pathogenic biallelic PTPN23 alterations cause a varied clinical spectrum comprising of complex HSP associated with microcephaly, which may occur without intellectual impairment or involve more severe neurological disease. Together, these findings highlight the importance of the inclusion of the PTPN23 gene on HSP gene testing panels globally.
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1038/ejhg.2016.146
发表时间：
2017-02
期刊：
European journal of human genetics : EJHG
影响因子：
--
作者：
Trujillano D;Bertoli-Avella AM;Kumar Kandaswamy K;Weiss ME;Köster J;Marais A;Paknia O;Schröder R;Garcia-Aznar JM;Werber M;Brandau O;Calvo Del Castillo M;Baldi C;Wessel K;Kishore S;Nahavandi N;Eyaid W;Al Rifai MT;Al-Rumayyan A;Al-Twaijri W;Alothaim A;Alhashem A;Al-Sannaa N;Al-Balwi M;Alfadhel M;Rolfs A;Abou Jamra R
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