Linkage analysis and gene mapping of one Chinese family with benign familial infantile convulsions
ZHOU Xi-Hui, MA Ai-Qun, LIU Xiao-Hong, HUANG Chen, ZHANG Yan-Min, SHI Rui-Ming
Department of Pediatrics, First Affiliated Hospital, Medical College of Xi'an Jiaotong University/Ion Channel Disease Laboratory, Environment and Disease Associated Gene Ministry of Education Intensive Laboratory, Xi'an 710061, China. Email: zhouxih@mail.xjtu.edu.cn
Abstract：OBJECTIVE: The present study performed linkage analysis and gene mapping to find the possible chromosome locus harboring in one family with benign familial infantile convulsions (BFIC) and investigate the possible molecular pathogenesis of BFIC. METHODS: A four-generation family with BFIC was investigated. The family was genotyped using eight hypervariable microsatellite markers covering four loci: D19S245 and D19S250 for the 19q12-13.1 region, D16S3131 and D16S3133 for the 16p12-q12 region, D2S156 and D2S286 for the 2q24 region, and D20S480 and D20S481 for the 20q13.3 region. Polymorphism fragments were amplified using polymerase chain reaction (PCR) method. PCR products for the markers were subjected to electrophoresis on 8% denatured polyacrylamide gel and silver staining for length judgment of amplification fragment. Linkage analysis was performed by use of MLINK in the LINKAGE computer package. Two-point LOD scores were calculated to estimate the linkage relationship. RESULTS: The two-point LOD scores were less than -2.0 for the genetic markers at chromosomes 19q12-13.1, 16p12-q12 and 2q24 at the recombination rate between 0.000 and 0.01. The two-point LOD scores for D20S481 at the 20q13.3 region were 0.3 and 0.25 at the recombination rate of 0.000 and 0.01, respectively. CONCLUSIONS: There is no evidence that this family with BFIC is linked to one of the following loci: 19q12-13.1, 16p12-q12 and 2q24, but a possible linkage with 20q13.3 region cannot be excluded.［Chin J Contemp Pediatr, 2010, 12 (2):89-92］
ZHOU Xi-Hui,MA Ai-Qun,LIU Xiao-Hong et al. Linkage analysis and gene mapping of one Chinese family with benign familial infantile convulsions[J]. CJCP, 2010, 12(2): 89-92.
［1］Striano P, Lispi ML, Gennaro E, Madia F, Traverso M, Bordo L, et al. Linkage analysis and disease models in benign familial infantile seizures: a study of 16 families［J］. Epilepsia, 2006, 47(6):1029-34.
［2］Li HY, Li N, Jiang H, Shen L, Guo JF, Zhang RX, et al. A novel genetic locus for benign familial infantile seizures maps to chromosome 1p36.12-p35.1［J］. Clin Genet, 2008, 74(5):490-492.
［3］Xiao B, Deng F-Y, Xiong G, Wang K, Zhang J, Chen XD, et al. Clinical and genetic study on a new chinese family with benign familial infantile seizures［J］. Europ J Neurol, 2005, 12:344-349.
［4］Heron SE, Cox K, Grinton BE, Zuberi SM, Kivity S, Afawi Z, et al. Deletions or duplications in KCNQ2 can cause benign familial neonatal seizures［J］. J Med Genet, 2007, 44(12):791-796.
［6］Fukuyama Y. Borderland of epilepsy with special reference to febrile convulsions and so-called infantile convulsions［J］. Seishin-Igaku (Clini Psychiatry), 1963, 5: 211-223.
［7］Vigevano F, Fusco L, Di Capua M, Ricci S, Sebastianelli R, Lucchini P. Benign familial infantile convulsions［J］. Eur J Peditr, 1992, 151(8): 608-612.
［8］Engel J Jr; International League Against Epilepsy(ILAE). A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on classification and terminology［J］. Epilesia, 2001, 42(6): 796-803.
［9］Guipponi M, Rivier F, Vigevano F, Beck C, Crespel A, Echenne B, et al. Linkage mapping of benign familial infantile convulsion (BFIC) to chromosome 19q［J］. Hum Mol Genet, 1997, 6(3): 473-477.
［10］Szepetowski P, Rochette J, Berqiun P, Piussan C, Lathrop GM, Monaco AP. Familial infantile convulsions and paroxysmal choreoathetosis: a new neurological syndrome linked to the pericentromeric region of human chromosome 16［J］. Am J Hum Genet, 1997, 61(4): 889-898.
［11］Caraballo R, Pavek S, Lemainque A, Gastaldi M, Echenne B, Motte J, et al. Linkage of benign familial convulsion to chromosome 16p12-q12 suggests allelism to the infantile convulsion and choreoathetosis syndrome. Am J Hum Genet［J］. 2001, 68(3): 788-794.
［12］Malacarne M, Gennaro E, Madia F, Pozzi S, Vacca D, Barone B, et al. benign familial infantile convulsions: mapping of a novel locus on chromosome 2q24 and evidence for genetic heterogeneity［J］. Am J Hum Genet, 2001, 68(6): 1521-1526.
［13］Vanmolkot KR, Kors EE, Hottenga JJ, Terwindt GM, Haan J, Hoefnagels WA, et al. Novel mutations in the Na+, K+-ATPase pump gene ATP1A2 associated with familial hemiplegic migraine and benign familial infantile convulsions［J］. Ann Neurol, 2003, 54(3): 360-366.
［14］Martinelli Boneschi F, Aridon P, Zara F, Guerrini R, Marini C, De Fusco M, et al. No evidence of ATP1A2 involvement in 12 multiplex Italian families with benign familial infantile seizures［J］. Neurosci Lett, 2005, 388(2):71-74.
［15］Striano P, Bordo L, Lispi ML, Specchio N, Minetti C, Vigevano F, et al. A novel SCN2A mutation in family with benign familial infantile seizures［J］. Epilepsia, 2006 , 47(1): 218-220.
［18］Li HY, Li N, Jiang H, Shen L, Guo JF, Zhang RX, et al. A novel genetic locus for benign familial infantile seizures maps to chromosome 1p36.12-p35.1［J］. Clin Genet, 2008, 74(5):490-492.
