Four novel compound heterozygous mutations in C5orf42 gene in patients with pure and mild Joubert syndrome

2020 ◽  
Vol 80 (6) ◽  
pp. 455-463
Author(s):  
Qiuyan Liu ◽  
Haiqiao Wang ◽  
Jianhui Zhao ◽  
Zhicui Liu ◽  
Dianrong Sun ◽  
...  
Keyword(s):  
Joubert Syndrome ◽  
Compound Heterozygous ◽  
Compound Heterozygous Mutations

scholarly journals Novel CC2D2A compound heterozygous mutations cause Joubert syndrome

2016 ◽  
Vol 15 (1) ◽  
pp. 305-308 ◽  
Author(s):  
Daimin Xiao ◽  
Chunli Lv ◽  
Zhimin Zhang ◽  
Mingsong Wu ◽  
Xiang Zheng ◽  
...  
Keyword(s):  
Joubert Syndrome ◽  
Compound Heterozygous ◽  
Compound Heterozygous Mutations

Primary Microcephaly With Anterior Predominant Pachygyria Caused by Novel Compound Heterozygous Mutations in ASPM

2015 ◽  
Vol 52 (5) ◽  
pp. e7-e8 ◽  
Author(s):  
Kazuyuki Nakamura ◽  
Takehiko Inui ◽  
Fuyuki Miya ◽  
Yonehiro Kanemura ◽  
Nobuhiko Okamoto ◽  
...  
Keyword(s):  
Compound Heterozygous ◽  
Primary Microcephaly ◽  
Compound Heterozygous Mutations

Molecular basis of ciliary defects caused by compound heterozygous IFT144/WDR19 mutations found in cranioectodermal dysplasia

2021 ◽  
Author(s):  
Yamato Ishida ◽  
Takuya Kobayashi ◽  
Shuhei Chiba ◽  
Yohei Katoh ◽  
Kazuhisa Nakayama
Keyword(s):  
Protein Trafficking ◽  
Primary Cilia ◽  
Intraflagellar Transport ◽  
Missense Variant ◽  
Cellular Level ◽  
Compound Heterozygous ◽  
Hypomorphic Allele ◽  
Genes Encoding ◽  
Specific Proteins ◽  
Compound Heterozygous Mutations

Abstract Primary cilia contain specific proteins to achieve their functions as cellular antennae. Ciliary protein trafficking is mediated by the intraflagellar transport (IFT) machinery containing the IFT-A and IFT-B complexes. Mutations in genes encoding the IFT-A subunits (IFT43, IFT121/WDR35, IFT122, IFT139/TTC21B, IFT140, and IFT144/WDR19) often result in skeletal ciliopathies, including cranioectodermal dysplasia (CED). We here characterized the molecular and cellular defects of CED caused by compound heterozygous mutations in IFT144 [the missense variant IFT144(L710S) and the nonsense variant IFT144(R1103*)]. These two variants were distinct with regard to their interactions with other IFT-A subunits and with the IFT-B complex. When exogenously expressed in IFT144-knockout (KO) cells, IFT144(L710S) as well as IFT144(WT) rescued both moderately compromised ciliogenesis and the abnormal localization of ciliary proteins. As the homozygous IFT144(L710S) mutation was found to cause autosomal recessive retinitis pigmentosa, IFT144(L710S) is likely to be hypomorphic at the cellular level. In striking contrast, the exogenous expression of IFT144(R1103*) in IFT144-KO cells exacerbated the ciliogenesis defects. The expression of IFT144(R1103*) together with IFT144(WT) restored the abnormal phenotypes of IFT144-KO cells. However, the coexpression of IFT144(R1103*) with the hypomorphic IFT144(L710S) variant in IFT144-KO cells, which mimics the genotype of compound heterozygous CED patients, resulted in severe ciliogenesis defects. Taken together, these observations demonstrate that compound heterozygous mutations in IFT144 cause severe ciliary defects via a complicated mechanism, where one allele can cause severe ciliary defects when combined with a hypomorphic allele.

Afibrinogenemia with two compound heterozygous mutations in FGA gene

Haemophilia ◽  
2021 ◽  
Author(s):  
Guillaume Feugray ◽  
Paul Billoir ◽  
Alessandro Casini ◽  
M. Neerman‐Arbez ◽  
Virginie Barbay ◽  
...  
Keyword(s):  
Compound Heterozygous ◽  
Compound Heterozygous Mutations
Sign in / Sign up

Export Citation Format

Share Document