Centre for Arab Genomic Studies Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences
Home About CAGS CTGA Database Publications Newsletter FAQs News Links عربي

Spastic Paraplegia 35, Autosomal Recessive


Alternative Names
SPG35

WHO International Classification of Diseases
Diseases of the nervous system > Systemic atrophies primarily affecting the central nervous system

OMIM Number
612319

Gene Map Locus
16q21-q23.1

Mode of Inheritance
Autosomal recessive

Med. Sea

Tunisia

Med. Sea

Lebanon

Syria

Iraq

Asia

Morocco

Algeria

Libya

Egypt

Palestine

Jordan

Kuwait

The Gulf

Mauritania

Sudan

KSA

Bahrain

Qatar

Eritrea

Red Sea

Yemen

Oman

X

UAE

Africa

Djibouti

Somalia

Comoros

Indian

Ocean

Description

The hereditary spastic paraplegias (HSPs) refer to a group of neurodegenerative disorders, characterized by upper motor neuron degeneration leading to progressive spasticity and weakness of the lower limbs. This group of diseases is both clinically and genetically heterogenous, with several separate loci having been mapped. SPG35 is a recently described subtype of spastic paraplegia. Clinically, SPG35 is a severe form of the paraplegia, following a progressive course, and is associated with intellectual disability. Radiologically, the disease shows features of leukodystrophy.

There are no specific treatments to prevent HSP. Management consists of symptomatic treatment and regular physical therapy to strengthen muscles.

Molecular Genetics

SPG35 has been found to be caused due to mutations in the FA2H (Fatty Acid 2 Hydroxylase) gene. It is not clear how defects in this gene could play a role in the development of SPG35. However, it is likely that abnormal hydroxylation of myelin galactocerebroside lipid components could be involved.


Epidemiology in the Arab World

Oman

Dick et al. (2008) studied a large consanguineous Omani family with an autosomal recessive form of HSP. The disease had a progressive course in this family and was associated with intellectual disability. In addition, two affected individuals also had seizures. Brain MRI revealed white matter abnormalities indicating leukodystrophy. Whole genome analysis identified a 20.4 Mb region of homozygozity on chromosome 16q. Two putative candidate genes in this region, Dynein, cytoplasmic 1, light intermediate chain 2 (DYNC1LI2) and vacuolar protein sorting 4 homolog A (VPS4A) were screened for mutations. However, none were found. Dick et al. (2008) stated that this was a novel form of autosomal recessive HSP and named it SPG35. Later, Dick et al. (2010) found mutations in the FA2H gene in the same family to be the underlying cause of the condition. They also detected significantly reduced function of the F2H enzyme in affected patients.

References

  1. Dick KJ, Al-Mjeni R, Baskir W, Koul R, Simpson MA, Patton MA, Raeburn S, Crosby AH. A novel locus for an autosomal recessive hereditary spastic paraplegia (SPG35) maps to 16q21-q23. Neurology. 2008; 71(4):248-52.
  2. Dick KJ, Eckhardt M, Paisán-Ruiz C, Alshehhi AA, Proukakis C, Sibtain NA, Maier H, Sharifi R, Patton MA, Bashir W, Koul R, Raeburn S, Gieselmann V, Houlden H, Crosby AH. Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35). Hum Mutat. 2010; 31(4):E1251-60.

Related CTGA Records

Links
http://rarediseases.about.com/cs/hs1/a/110103.htm
http://www.wemove.org/hsp/

Contributors
Pratibha Nair: 30.6.2010

Edit History
Tasneem: 28.4.2011

Notes
To contribute with your findings to the content of this record, please fill the CTGA Database Information Submission Form and email it, along with supportive documents, to cags@emirates.net.ae.




Copyright © Centre for Arab Genomic Studies. All rights reserved.