Novel PEX11B Mutations Extend the Peroxisome Biogenesis Disorder 14B Phenotypic Spectrum and Underscore Congenital Cataract as an Early Feature

@article{Taylor2017NovelPM,
  title={Novel PEX11B Mutations Extend the Peroxisome Biogenesis Disorder 14B Phenotypic Spectrum and Underscore Congenital Cataract as an Early Feature},
  author={Rachel L. Taylor and Mark T. Handley and Sarah Waller and Christopher Campbell and J E Urquhart and Alison M. Meynert and Jamie M. Ellingford and D E Donnelly and Gisela Wilcox and I. Chris Lloyd and Helen R Mundy and David R. Fitzpatrick and Charu Deshpande and Jill Clayton-Smith and Graeme C. M. Black},
  journal={Investigative ophthalmology \& visual science},
  year={2017},
  volume={58},
  pages={594 - 603}
}
Purpose Peroxisomes perform complex metabolic and catabolic functions essential for normal growth and development. Mutations in 14 genes cause a spectrum of peroxisomal disease in humans. Most recently, PEX11B was associated with an atypical peroxisome biogenesis disorder (PBD) in a single individual. In this study, we identify further PEX11B cases and delineate associated phenotypes. Methods Probands from three families underwent next generation sequencing (NGS) for diagnosis of a multisystem… 

Figures from this paper

Variant analysis of PEX11B gene from a family with peroxisome biogenesis disorder 14B by whole exome sequencing
TLDR
PBD14B is an autosomal recessive peroxisome biogenesis disorder characterized clinically by mild intellectual disability, congenital cataracts, progressive hearing loss, and polyneuropathy.
A Mouse Model System to Study Peroxisomal Roles in Neurodegeneration of Peroxisome Biogenesis Disorders.
TLDR
This chapter overviews the phenotypes of Pex-inactivated mice and the current understanding of the pathogenesis underlying PBDs as well as illustrating the illustrations of detailed pathological phenotypes in the mutant mice.
NEUROMETABOLIC DISORDER A Novel Mutation in PEX 11 β Gene
TLDR
Peroxisomes are membrane-enclosed organelles involved in a variety of metabolic pathways including αand β-oxidation of fatty acids and synthesis of bile acids, cholesterol, and plasmalogens and the phenotypic presentation can range NEUROMETABOLIC DISORDER.
Genetic landscape of isolated pediatric cataracts: extreme heterogeneity and variable inheritance patterns within genes
TLDR
Exome sequencing continues to be successful in identifying novel genes associated with congenital cataract but is hindered by the extreme genetic heterogeneity of this condition.
Mitochondrial fission factor (MFF) is a critical regulator of peroxisome maturation
TLDR
It is shown that MFF deficiency does not cause alterations to overall peroxisomal biochemical function, however, loss of MFF results in reduced import-competency of the peroxISomal compartment and leads to the accumulation of pre-peroxisome membrane structures in MFF-deficient cells.
Fission Impossible (?)—New Insights into Disorders of Peroxisome Dynamics
TLDR
The clinical phenotypes and pathophysiology of patients with defects in the key division proteins DRP1, MFF, and PEX11β as well as in the peroxisome–ER tether ACBD5 are summarized.
A Functional SMAD2/3 Binding Site in the PEX11β Promoter Identifies a Role for TGFβ in Peroxisome Proliferation in Humans
TLDR
It is determined that serum stimulation, long-chain fatty acid supplementation and TGFβ application all increase peroxisome elongation, a prerequisite for proliferation.
The peroxisome: an update on mysteries 2.0
TLDR
This review intends to highlight recent discoveries, advancements and trends in peroxisome research, and present an update as well as a continuation of two former review articles addressing the unsolved mysteries of this astonishing organelle.
Peroxisome: Metabolic Functions and Biogenesis.
TLDR
Functional delineation of the peroxins has revealed that peroxisome biogenesis comprises the processes, involving per oxisomal membrane assembly, matrix protein import, division, and proliferation.
Eye involvement in inherited metabolic disorders
  • J. Davison
  • Medicine
    Therapeutic advances in ophthalmology
  • 2020
TLDR
awareness of inherited metabolic disorders is important to facilitate early diagnosis and in some cases instigate early treatment if a patient presents with eye involvement suggestive of a metabolic disorder.
...
...

References

SHOWING 1-10 OF 27 REFERENCES
A novel defect of peroxisome division due to a homozygous non-sense mutation in the PEX11β gene
TLDR
A novel isolated defect in peroxisome division is presented, which indicates that peroxISomal defects exist, which cannot be diagnosed by standard laboratory investigations.
Zellweger Spectrum Disorder with Mild Phenotype Caused by PEX2 Gene Mutations.
TLDR
The clinical phenotype of a 51-year-old Italian man referred to us because of a clinical picture characterized by ataxia, areflexia, nystagmus, and strabismus, with childhood onset and slowly progressive course suggests that genetic screening of PEX2 is warranted in children and adults with otherwise unexplained autosomal recessive ataxian disorders.
Diagnostic utility of whole exome sequencing in patients showing cerebellar and/or vermis atrophy in childhood
TLDR
The utility of whole exome sequencing for genetic diagnosis of childhood cerebellar and/or vermis atrophy is demonstrated and the main clinical features of ten patients were nonspecific and mixed.
Personalized diagnosis and management of congenital cataract by next-generation sequencing.
Human disorders of peroxisome metabolism and biogenesis.
A robust model for read count data in exome sequencing experiments and implications for copy number variant calling
TLDR
This analysis identified two novel causative deletions in the genes GATA2 and DOCK8 and introduced ExomeDepth, a new CNV calling algorithm designed to control for technical variability between samples in exome sequence data.
Metabolic functions of peroxisomes in health and disease.
...
...