Novel Compound Missense and Intronic Splicing Mutation in ALDH18A1 Causes Autosomal Recessive Spastic Paraplegia.

Frontiers in Neurology
Yi-Jun ChenXiang Lin

Abstract

Background: Hereditary spastic paraplegia (HSP) caused by mutations in ALDH18A1 have been reported as spastic paraplegia 9 (SPG9), with autosomal dominant and autosomal recessive transmission (SPG9A and SPG9B). SPG9 is rare and has shown phenotypic and genotypic heterogeneity in previous reports. Methods: This study screened ALDH18A1 mutations in autosomal recessive HSP patients using combined whole exome sequencing and RNA splicing analysis. We conducted in silico investigations, co-segregation analysis, and ELISA-based analysis of P5CS (Δ1-pyrroline-5-carboxylate synthetase; encoded by ALDH18A1) concentration to validate the pathogenicity of the detected ALDH18A1 variants. All previously reported bi-allelic ALDH18A1 mutations and cases were reviewed to summarize the genetic and clinical features of ALDH18A1-related HSP. Results: A novel missense mutation c.880T>C, p.S294P and an intronic splicing mutation c.-28-13A>G were both detected in ALDH18A1 in an autosomal recessive family presenting with a complicated form HSP. ELISA assays revealed significantly decreased P5CS concentration in the proband's plasma compared with that in the healthy controls. Moreover, review of previously reported recessive cases showed that SPG9B pat...Continue Reading

References

May 20, 1999·American Journal of Human Genetics·S N TeraokaP Concannon
Feb 26, 2009·Cell·Thomas A CooperGideon Dreyfuss
Jan 22, 2010·Protein Science : a Publication of the Protein Society·Isabel Pérez-ArellanoJavier Cervera
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Sep 8, 2012·Science·Matthew T MauranoJohn A Stamatoyannopoulos
Nov 5, 2014·Nature·Kyle Kai-How FarhBradley E Bernstein
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
May 31, 2015·Brain : a Journal of Neurology·Marie CoutelierGiovanni Stevanin
Feb 10, 2016·Annals of Neurology·Rebecca SchüleLudger Schöls
May 25, 2016·Brain : a Journal of Neurology·Eleanna KaraHenry Houlden
Apr 24, 2018·Journal of Applied Genetics·Abramowicz Anna, Gos Monika
Jun 20, 2018·Journal of Human Genetics·Kishin KohUNKNOWN Japan Spastic Paraplegia Research Consortium
Jul 8, 2018·Molecular Neurodegeneration·En-Lin DongXiang Lin
Nov 14, 2018·Bioinformatics·Shifu ChenJia Gu
Jan 22, 2019·Cell·Kishore JaganathanKyle Kai-How Farh
Jun 17, 2019·Brain : a Journal of Neurology·Xiang LinWan-Jin Chen
Aug 5, 2019·Lancet Neurology·Samuel ShribmanThomas T Warner
Aug 14, 2019·Annals of Clinical and Translational Neurology·Pamela MaginiEmanuele Panza
Oct 21, 2019·Molecular Diagnosis & Therapy·Miao ZhaoXiang Lin
Dec 20, 2019·Annals of Clinical and Translational Neurology·Edgard VerduraAurora Pujol
Aug 17, 2020·Brain & Development·Tibor KalmárLászló Sztriha

❮ Previous
Next ❯

Software Mentioned

MutationTaster
gnomAD
PolyPhen
fastp
SpliceAI
Illumina SpliceAI
Genome Analysis Toolkit ( GATK )
GraphPad Prism
ANNOVAR
CADD

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society
David F G J WolthuisEva Morava
© 2021 Meta ULC. All rights reserved