JOURNAL ARTICLE

Clinical spectrum of SCN2A mutations expanding to Ohtahara syndrome

Kazuyuki Nakamura, Mitsuhiro Kato, Hitoshi Osaka, Sumimasa Yamashita, Eiji Nakagawa, Kazuhiro Haginoya, Jun Tohyama, Mitsuko Okuda, Takahito Wada, Shuichi Shimakawa, Katsumi Imai, Saoko Takeshita, Hisako Ishiwata, Dorit Lev, Tally Lerman-Sagie, David E Cervantes-Barragán, Camilo E Villarroel, Masaharu Ohfu, Karin Writzl, Barbara Gnidovec Strazisar, Shinichi Hirabayashi, David Chitayat, Diane Myles Reid, Kiyomi Nishiyama, Hirofumi Kodera, Mitsuko Nakashima, Yoshinori Tsurusaki, Noriko Miyake, Kiyoshi Hayasaka, Naomichi Matsumoto, Hirotomo Saitsu
Neurology 2013 September 10, 81 (11): 992-8
23935176

OBJECTIVE: We aimed to investigate the possible association between SCN2A mutations and early-onset epileptic encephalopathies (EOEEs).

METHODS: We recruited a total of 328 patients with EOEE, including 67 patients with Ohtahara syndrome (OS) and 150 with West syndrome. SCN2A mutations were examined using high resolution melt analysis or whole exome sequencing.

RESULTS: We found 14 novel SCN2A missense mutations in 15 patients: 9 of 67 OS cases (13.4%), 1 of 150 West syndrome cases (0.67%), and 5 of 111 with unclassified EOEEs (4.5%). Twelve of the 14 mutations were confirmed as de novo, and all mutations were absent in 212 control exomes. A de novo mosaic mutation (c.3976G>C) with a mutant allele frequency of 18% was detected in one patient. One mutation (c.634A>G) was found in transcript variant 3, which is a neonatal isoform. All 9 mutations in patients with OS were located in linker regions between 2 transmembrane segments. In 7 of the 9 patients with OS, EEG findings transitioned from suppression-burst pattern to hypsarrhythmia. All 15 of the patients with novel SCN2A missense mutations had intractable seizures; 3 of them were seizure-free at the last medical examination. All patients showed severe developmental delay.

CONCLUSIONS: Our study confirmed that SCN2A mutations are an important genetic cause of OS. Given the wide clinical spectrum associated with SCN2A mutations, genetic testing for SCN2A should be considered for children with different epileptic conditions.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
23935176
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"