Next-Generation Sequencing Reveals Novel Homozygous Missense Variant c.934T > C in POLR1C Gene Causing Leukodystrophy and Hypomyelinating Disease

被引:1
|
作者
Naseer, Muhammad Imran [1 ,2 ]
Abdulkareem, Angham Abdulrahman [1 ,3 ]
Pushparaj, Peter Natesan [1 ,2 ,4 ]
Saharti, Samah [5 ]
Muthaffar, Osama Y. [6 ]
机构
[1] King Abdulaziz Univ, Ctr Excellence Genom Med Res, Jeddah, Saudi Arabia
[2] King Abdulaziz Univ, Fac Appl Med Sci, Dept Med Lab Technol, Jeddah, Saudi Arabia
[3] King Abdulaziz Univ, Fac Sci, Dept Biochem, Jeddah, Saudi Arabia
[4] Saveetha Inst Med & Tech Sci, Saveetha Dent Coll & Hosp, Ctr Transdisciplinary Res, Dept Pharmacol, Chennai, India
[5] King Abdulaziz Univ, Dept Pathol & Microbiol, Jeddah, Saudi Arabia
[6] King Abdulaziz Univ, Fac Med, Dept Pediat, Jeddah, Saudi Arabia
来源
FRONTIERS IN PEDIATRICS | 2022年 / 10卷
关键词
POLR1C; intellectual developmental disorder; leukodystrophy; hypomyelinating disease; WES; Saudi family; III CAUSE; MUTATIONS; SPECTRUM; SUBUNIT; ATAXIA;
D O I
10.3389/fped.2022.862722
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Leukodystrophies are a diverse group of genetically established disorders categorized by unusual white matter changes on brain imaging. Hypomyelinating leukodystrophies (HLDs) are a group of neurodevelopmental disorders that affect myelin sheath development in the brain. These disorders are categorized as developmental delay, spasticity, hypotonia, and intellectual disabilities. We describe a patient with developmental delay, cerebellar ataxia, spasticity, hypotonia, and intellectual disability from a healthy family member. Whole exome sequencing (WES) was performed to identify causative variants, which were further analyzed by bioinformatic analysis. WES was performed, and Sanger sequencing-based segregation analysis confirmed the presence of the homozygous missense variants of NM_203290.3 c.934T > C p.Ser312Pro of RNA polymerase I and III subunit C (POLR1C) gene in this patient and heterozygous variant in the unaffected carrier father and mother, supporting the pathogenicity and inheritance pattern of this variant. Furthermore, the variant identified by WES was validated in healthy controls (n = 100) using Sanger sequencing analysis. Finally, our study explained the important use of WES in disease diagnosis and provided further evidence that the variant in the POLR1C gene may play an important role in the development of hypomyelinating leukodystrophy in Saudi families.
引用
收藏
页数:8
相关论文
共 50 条
  • [1] Novel Mutation in the POLR1C Gene Causing Hypomyelinating Leukodystrophy in an Adult
    Yadav, Nishtha
    Saini, Jitender
    Nagappa, Madhu
    NEUROLOGY-CLINICAL PRACTICE, 2021, 11 (03) : E367 - E369
  • [2] A Novel POLR1C Mutation Causing Autosomal Recessive Adult-Onset Leukodystrophy
    Geschwind, Michael
    Kim, Mee-Ohk
    Wahl, Colleen
    Gahl, William
    Toro, Camilo
    NEUROLOGY, 2016, 86
  • [3] Next-generation sequencing reveals a novel HLA-C allele, HLA-C*15:255
    Rakhmanov, Mirzokhid
    Bernheiden, Martin
    Verboom, Murielle
    Emmerich, Florian
    HLA, 2023, 102 (01) : 100 - 102
  • [4] Hb Mizuho (HBB: c.206T>C): Pitfalls of Screening Tests in an Unstable Hemoglobin Variant Diagnosed after Targeted Next-Generation Sequencing
    Yadav, Diksha D.
    Jamwal, Manu
    Singh, Namrata
    Sharma, Ritika
    Das, Reena
    Trehan, Amita
    Bansal, Deepak
    Chhabra, Sanjeev
    Sharma, Prashant
    HEMOGLOBIN, 2021, 45 (05) : 338 - 340
  • [5] A novel β-thalassemia variant at HBB:c.14delC (Codon 4, -C) identified via next-generation sequencing
    Chen, Junkun
    Lin, Shaobin
    Gan, Jinghui
    Xin, Xiaoqin
    Huang, Jungao
    HEMATOLOGY, 2020, 25 (01) : 400 - 404
  • [6] A novel HLA-C*18 variant allele, HLA-C*18:20, identified by next-generation sequencing
    Mclamb, Nathan
    Jennemann, Jo-Ellen
    Willey, Patricia
    Liu, Chang
    HLA, 2024, 104 (02)
  • [7] THE C.-755C>T VARIANT IN THE CFTR GENE MOST LIKELY REPRESENTS A NON-DISEASE CAUSING POLYMORPHIC VARIANT
    Cherny, S.
    Keiles, S. B.
    PEDIATRIC PULMONOLOGY, 2009, : 277 - 277
  • [8] Novel homozygous missense mutation c.1654G>T in the ALOX12B gene causing congenital ichthyosiform erythroderma
    Mae, Kotoe
    Kawakami, Yoshio
    Kajita, Ai
    Takeichi, Takuya
    Noda, Tatsuhiro
    Hirai, Yoji
    Akiyama, Masashi
    Morizane, Shin
    JOURNAL OF DERMATOLOGY, 2023, 50 (01): : E37 - E38
  • [9] A novel HLA-C*07 variant allele, HLA-C*07:01:01:141, identified by next-generation sequencing
    Kouniaki, Diamanto
    Athanassiades, Theofilos
    Tsirogianni, Alexandra
    HLA, 2024, 104 (03)
  • [10] Pachydermoperiostosis of the complete type: A novel missense mutation c.101T > C in the SLCO2A1 gene
    Ma, Wenbin
    Guo, Shuqin
    Li, Yan
    Li, Zhihong
    EUROPEAN JOURNAL OF MEDICAL GENETICS, 2017, 60 (08) : 433 - 436