Clinical characteristics and in silico analysis of congenital pseudarthrosis of the tibia combined with neurofibromatosis type 1 caused by a novel NF1 mutation
Congenital pseudarthrosis of the tibia (CPT) is a rare congenital bone malformation, which has a strong relationship with Neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant disease leading to multisystem disorders. Here, we presented the genotypic and phenotypic characteristics of one uniq...
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Published in | Frontiers in genetics Vol. 13; p. 991314 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
28.09.2022
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Subjects | |
Online Access | Get full text |
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Summary: | Congenital pseudarthrosis of the tibia (CPT) is a rare congenital bone malformation, which has a strong relationship with Neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant disease leading to multisystem disorders. Here, we presented the genotypic and phenotypic characteristics of one unique case of a five-generation Chinese family. The proband was CPT accompanied with NF1 due to
NF1
mutation. The proband developed severe early-onset CPT combined with NF1 after birth. Appearance photos and X-ray images of the left limb of the proband showed significant bone malformation. Slit-lamp examination showed Lisch nodules in both eyes of the proband. Whole-exome sequencing (WES) and Sanger sequencing confirmed the truncation variant of
NF1
(c.871G>T, p. E291
*
). Sequence conservative and evolutionary conservation analysis indicated that the novel mutation (p.E291
*
) was highly conserved. The truncated mutation led to the loss of functional domains, including CSRD, GRD, TBD, SEC14-PH, CTD, and NLS. It may explain why the mutation led to a severe clinical feature. Our report expands the genotypic spectrum of NF1 mutations and the phenotypic spectrum of CPT combined with NF1. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Likui Feng, The Rockefeller University, United States Jinsong Wang, Hubei Normal University, China Haiyun Li, Xi’an Jiaotong University, China These authors have contributed equally to this work This article was submitted to Genetics of Common and Rare Diseases, a section of the journal Frontiers in Genetics Edited by: Yonghu Sun, Shandong Provincial Hospital of Dermatology, China |
ISSN: | 1664-8021 1664-8021 |
DOI: | 10.3389/fgene.2022.991314 |