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Prevalent MLC1 founder mutation causing autosomal recessive Megalencephalic Leukoencephalopathy in consanguineous Palestinian families

Reham A. Khalaf-Nazzal1* and Rasha T. Doulani2*
  • 1 An-Najah National University, Genetics and Developmental Neuroscience, Palestine
  • 2 Medical student at Faculty of Medicine and Health Sciences, Clinical department, Palestine

Megalencephalic leukoencepohalopathy with subcortical cysts (MLC) is a rare hereditary disease that manifests as early-onset macrocephaly, accompanied by mild but progressive gross motor developmental delay, and seizures that maybe provoked by trauma. Later in the disease course, significant spasticity and ataxia develop, which may be accompanied by mild intellectual deterioration. Brain MRI shows characteristic abnormalities, including diffuse supratentorial white matter swelling and the presence of subcortical cysts in the anterior temporal region and frontoparietal region. The severity of the disease is variable according to the phenotype. In the classical phenotype; Patients present with early-onset clinical picture. Macrocephaly is present at birth or in the first year of life and is associated with mild delay in gross motor development and progressive evolution of pyramidal symptoms and sign. Cerebellar ataxia may develop later in life. Most children become wheelchair-dependent as teenagers. Intellectuality is normal or mildly affected later in the disease course. Mutations in MLC1 gene is responsible for most patients with the classical phenotype, and are inherited in an autosomal recessive manner. An atypical improving phenotype; has a similar initial presentation with improvement in the clinical picture later in life. This phenotype is caused by heterozygous mutations in the HEPACAM gene. In this study, we sequenced the entire coding region of MLC1 gene in six Palestinian patients coming from four different parents with consanguineous marriages. All studied patients originate from several Palestinian villages located in south and south east Nablus. We identified an MLC1 splice mutation in all of the studied patients. This highlights strong founder effect in this area, where marriage counseling and screening should be provided.

Acknowledgements

We thank Dr. Imen Dorboz and Professor Odile BOESPFLUG-TANGUY, Genetic disorders of the developing brain team , INSERM UMR1141, Paris, France.

References

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Keywords: MLC disease, Splice site mutation, consanguinity., Founder effect, autosomal recessive, Macrocephaly, leukoencephalopathy

Conference: 2nd International Conference on Educational Neuroscience, Abu Dhabi, United Arab Emirates, 5 Mar - 6 Mar, 2017.

Presentation Type: Poster Presentation

Topic: Educational Neuroscience

Citation: Khalaf-Nazzal RA and Doulani RT (2017). Prevalent MLC1 founder mutation causing autosomal recessive Megalencephalic Leukoencephalopathy in consanguineous Palestinian families. Conference Abstract: 2nd International Conference on Educational Neuroscience. doi: 10.3389/conf.fnhum.2017.222.00036

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Received: 23 Jan 2017; Published Online: 11 Dec 2017.

* Correspondence:
MD, PhD. Reham A Khalaf-Nazzal, An-Najah National University, Genetics and Developmental Neuroscience, Nablus, Palestine, reham.khalaf@icloud.com
Ms. Rasha T Doulani, Medical student at Faculty of Medicine and Health Sciences, Clinical department, Nablus, Palestine, Rashdoulani@yahoo.com