Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement.

Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement. Abstract Text:

Annagiusi Gargiulo,Renata Auricchio,Maria Vittoria Barone,Gabriella Cotugno,William Reardon,Peter J Milla,Andrea Ballabio,Alfredo Ciccodicola,Alberto Auricchio,

We have previously reported that an X-linked recessive form of chronic idiopathic intestinal pseudo-obstruction (CIIPX) maps to Xq28. To select candidate genes for the disease, we analyzed the expression in murine fetal brain and intestine of 56 genes from the critical region. We selected and sequenced seven genes and found that one affected male from a large CIIPX-affected kindred bears a 2-bp deletion in exon 2 of the FLNA gene that is present at the heterozygous state in the carrier females of the family. The frameshift mutation is located between two close methionines at the filamin N terminus and is predicted to produce a protein truncated shortly after the first predicted methionine. Loss-of-function FLNA mutations have been associated with X-linked dominant nodular ventricular heterotopia (PVNH), a central nervous system (CNS) migration defect that presents with seizures in females and lethality in males. Notably, the affected male bearing the FLNA deletion had signs of CNS involvement and potentially has PVNH. To understand how the severe frameshift mutation we found can explain the CIIPX phenotype and its X-linked recessive inheritance, we transiently expressed both the wild- type and mutant filamin in cell culture and found that filamin translation can start from either of the two initial methionines in these conditions. Therefore, translation of a normal shorter filamin can occur in vitro from the second methionine downstream of the 2-bp insertion we found. We confirmed this, demonstrating that the filamin protein is present in the patient's lymphoblastoid cell line that shows abnormal cytoskeletal actin organization compared with normal lymphoblasts. We conclude that the filamin N terminal region between the initial two methionines is crucial for proper enteric neuron development.

Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement. Publishing Authors By Initials

A Gargiulo,R Auricchio,MV Barone,G Cotugno,W Reardon,PJ Milla,A Ballabio,A Ciccodicola,A Auricchio,

For similar investigative techniques: genetic techniques: sequence analysis: sequence analysis, dna research abstracts see: investigative techniques: genetic techniques: sequence analysis: sequence analysis, dna research

PUBMED ID PMID:

MEDLINE DATE:

Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: American journal of human genetics

VOLUME: 80

Page Numbers: 751-8

Journal Abbreviation: Am. J. Hum. Genet.

ISSN: 0002-9297

DAY: 26

MONTH: 02

YEAR: 2007

Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370475

Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement. Keywords Mesh Terms:

KEYWORDS: Sequence Analysis, DNA

MESH TERMS: genetics

Chemical & Substance for Abstract: Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement. Information

Substance Name: filamins

Registry Number: 0

Grant and Affiliation Information for Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement.

AFFILIATION: Telethon Institute of Genetics and Medicine, Naples, Italy.

Country: United States

AGENCY: United States NEI

GRANT: 1R01EY015136-01

ACRONYM: EY

MEDLINETA: Am J Hum Genet

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement Related Publications

• AAV-mediated gene transfer for retinal diseases.
• Activity monitoring in heart failure patients with cardiac resynchronization therapy.
• Biochemical, Pathological, and Skeletal Improvement of Mucopolysaccharidosis VI After Gene Transfer to Liver but Not to Muscle.
• Comparison of Brain Natriuretic Peptide Plasma Levels Versus Logistic EuroSCORE in Predicting In-Hospital and Late Postoperative Mortality in Patients Undergoing Aortic Valve Replacement for Symptomatic Aortic Stenosis.
• Constitutive and AP20187-induced Ret activation in photoreceptors does not protect from light-induced damage.
• Coronary Sinus Visualization by 3-dimensional Real-time Echocardiography.
• Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement.
• Hormone-dependent nuclear export of estradiol receptor and DNA synthesis in breast cancer cells.
• In vitro effect of alpha-tocopherol on lysophosphatidylcholine-induced lens damage.
• Influence of left atrial and ventricular volumes on the relation between mitral valve annulus and coronary sinus.
• Inhibition of Estradiol Receptor/Src Association and Cell Growth by an Estradiol Receptor {alpha} Tyrosine-Phosphorylated Peptide.
• Inhibition of the SH3 domain-mediated binding of Src to the androgen receptor and its effect on tumor growth.
• Integrating signals between cAMP and MAPK pathways in breast cancer.
• Latent and potential coeliac disease.
• Long-term outcome in diabetic heart failure patients treated with cardiac resynchronization therapy.
• Mankind adaptation and present human health.
• Novel adeno-associated virus serotypes efficiently transduce murine photoreceptors.
• Preferential silencing of a common dominant rhodopsin mutation does not inhibit retinal degeneration in a transgenic model.
• Transglutaminase 1 deficiency and corneocyte collapse: an indication for targeted molecular screening in autosomal recessive congenital ichthyosis.
• Versatility of AAV vectors for retinal gene transfer.
• [Not Available.]
• [Not Available.]