J Korean Med Sci.  2005 Aug;20(4):670-673. 10.3346/jkms.2005.20.4.670.

A Novel Missense Mutation of Doublecortin: Mutation Analysis of Korean Patients with Subcortical Band Heterotopia

• Kim MK
• Park MS
• Kim BC
• Cho KH
• Kim YS
• Kim JH
• Lee MC
• Heo T
• Kim EY

• KMID: 1712752
• DOI: http://doi.org/10.3346/jkms.2005.20.4.670

Abstract

The neuronal migration disorders, X-linked lissencephaly syndrome (XLIS) and subcortical band heterotopia (SBH), also called "double cortex", have been linked to missense, nonsense, aberrant splicing, deletion, and insertion mutations in doublecortin (DCX) in families and sporadic cases. Most DCX mutations identified to date are located in two evolutionarily conserved domains. We performed mutation analysis of DCX in two Korean patients with SBH. The SBH patients had mild to moderate developmental delays, drug-resistant generalized seizures, and diffuse thick SBH upon brain MRI. Sequence analysis of the DCX coding region in Patient 1 revealed a c.386 C>T change in exon 3. The sequence variation results in a serine to leucine amino acid change at position 129 (S129L), which has not been found in other family members of Patient 1 or in a large panel of 120 control X-chromosomes. We report here a novel c.386 C>T mutation of DCX that is responsible for SBH.

Keyword

doublecortin protein; Subcortical Band Heterotopia; Mutation; Epilepsy

MeSH Terms

Adolescent
Adult
Base Sequence
Brain Diseases/*genetics/pathology
*Cerebral Cortex
Choristoma/*genetics/pathology
DNA Mutational Analysis
Female
Humans
Magnetic Resonance Imaging
Microtubule-Associated Proteins/*genetics
*Mutation, Missense
Neuropeptides/*genetics
Research Support, Non-U.S. Gov't

Figure

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  Fig. 1 Brain MRI scans of Patient 1 (A) and 2 (B) showing diffuse thin and thick subcortical band heterotopia, respectively.

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  Fig. 2 (A) Electropherogram of heterozygous c.386C>T (S129L) mutation (arrow) of DCX in Patient 1. Upper layer; normal sequence, lower layer; mutant sequence. (B) RFLP analysis using Mnl1 enzyme shows heterozygous mutant band pattern in Patient 1 (lane 6). Lane 1 and 2; controls. Lane 3; maternal grandmother, 4; mother, 5; father, and 7, 8; siblings of Patient 1. M: DNA size marker.

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