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Epilepsy
European Journal of Paediatric
Gene table: Epilepsy
Neurology
Mendelian
1:
55-57
(Frances Elmslie)
Disease
Primary
1997;
Mode of inheritance
Gene location
Gene symbol (gene product)
MIM
Key refs
EBNl EBNZ
121200 121201
16,17
epilepsies
Benign familial convulsions
neonatal
AD
2oq13 8q24
Benign familial convulsions
infantile
AD
1%
10
Autosomal dominant frontal lobe epilepsy
nocturnal
AD
2oq13
Partial epilepsy symptoms
auditory
AD
14
AR
8P
EPMR
Unverricht-Lundborg disease (Baltic myoclonus, Mediterranean myoclonus)
AR
21q22
EPMl (Cystatin
Infantile neuronal lipofuscinosis
AR
1~32
AR
llp15
CLNl (palmitoyl protein thioesterase) CLN2
AR
15q21-23
CLNC
AR
16~12
CLN3
204200
4, 11
AR
13q22
CLN5
256731
23
AR
6q23-25
254780
24
Complex
?6p ?8q24
254770 121210
3, 5, 9,18, 32, 33
with
Progressive epilepsy with mental retardation (Northern epilepsy) Progressive epilepsies
CHRNA4 (nAChR a4 subunit)
600513
22,27
600512
20
600143
28
254800
15,21
256730
12,30
204500
25
myoclonic
ceroid
Late infantile neuronal ceroid lipofuscinosis Variant late infantile neuronal ceroid lipofuscinosis Juvenile neuronal ceroid lipofuscinosis Finnish variant neuronal ceroid lipofuscinosis Lafora disease
B)
25
Epilepsy syndromes displaying complex inheritance Juvenile
myoclonic
epilepsy
Idiopathic generalized Febrile convulsions
epilepsy
Complex Complex
EJMl
?8q13-21
35 31
600669
(continued)
Correspondence: logo-3798/97/010055+3
Dr Frances
Elmslie, $18.00
Department
of Clinical
Genetics,
Institute
of Child
Health,
30 Guilford
Street,
0 1997
European
London Society
WC1 N 1EH, UK
of
Paediatric
Neurology
Gene
56
Disease
Mode of inheritance
Gene location
Gene (gene
AD
9q34 16~13
TSCl TSC2
15q13
ANCR (EC-AI’
symbol product)
tab/e:
F Elmslie
MIM
Key
refs
191100
6, 7, 13
Mendelian disorders including epilepsy as part of the phenotype Tuberous
sclerosis
191092
(tuberin) Angelman
AD
syndrome
105830
2, 14, 19
162200
1, 34
309550
29
ubiquitin-protein ligase) Neurofibromatosis
type
AD
1
NFl
17qll
(neurofibromin) Fragile
X-linked
X
FMR-1
xq27
(fragile X mental retardation protein)
Mitochondrial
disorders
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Myoclonic red fibres MIM:
epilepsy (MERRF)
Mendelian
with
inheritance
ragged
Maternal
tRNA-Leu WW
540000
8
Maternal
tRNA-Lys
545000
26
in Man.
References
Barker D, Wright E, Nguyen K et al. Gene for von Reckhnghausen neurofibromatosis is in the pericentromeric region of chromosome 17. Science 1987; 236: 1100-1102. Chan CT, Clayton-Smith J, Cheng XJ ef al. Molecular mechanisms in Angelman syndrome: a survey of 93 patients. 1 Med Genet 1993; 30: 895-902. Dumer M, Sander T, Greenberg DA et nl. Localisation of idiopathic generalised epilepsy on chromosome 6p in families of juvenile myoclonic epilepsy patients. Neurology 1991; 41: 1651-1655. Eiberg H, Gardiner RM, Mohr J. Batten disease (SpielmeyerSjGgren disease) and haptoglobins (HP):indication of linkage and assignment to chromosome 16. C/in Genet 1989; 36: 217218. ElmsIie FV, Williamson MP, Rees M et al. Linkage analysis of juvenile myoclonic epilepsy and microsatellite loci spanning 61 CM of human chromosome 6p in 19 nuclear pedigrees provides no evidence for a susceptibility locus in this region. Am j Hum Genet 1996; 59: 653-663.
8
9
10
11
12
13
European chromosome 16 tuberous sclerosis consortium. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell 2993; 75: 1305-1315.
14
Fryer AE, Chalmers A, Connor JM et al. Evidence that the gene for tuberous sclerosis is on chromosome 9. Lancet 1987; i: 659-661.
15
Goto Y, Nonaka I, Horai S et al. A mutation in the tRNA-leu (UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature 1990; 348: 651-653. Greenberg DA, Delgado-Escueta AV, Widelitz H et al. Juvenile myoclonic epilepsy may be linked to the BF and HLA loci on human chromosome 6. Am 1 Med Genet 1988; 31: 185-192. Guipponi M, Rivier F, Vigevano F et al. Linkage mapping of benign infantile convulsions (BFIC) to chromosome 19q. Hum Mol Gerlet 1997; 6: 473-477. The International Batten Disease Consortium. Isolation of a novel gene underlying Batten Disease, CLN3. Cell 1995; 82: 949-957. Jarvela I, SchIeutker J, Haataja L et al. Infantile form of neuronal ceroid lipofuscinosis (CLNl) maps to the short arm of chromosome 1. Genomics 1991; 9: 170-173. Kandt RS, Haines JL, Smith M et al. Linkage of an important gene locus to a chromosome 16 marker for polycystic kidney disease. Nature Gene1 1992; 2: 3741. Kishino T, Lalande M, Wagstaff J et al. UBE3A/E6-AP mutations cause Angehnan syndrome. Nature Gene1 1997; IS: 70-73. Lehesjoki A-E, Koskiniemi M, Sistonen P, et al. Localisation of a gene for progressive myoclonus epilepsy to chromosome 21q22. PNAS 1991; 88: 3696-3699.
57
Gene table: Epilepsy 16
Leppert M, Anderson VE, Quattlebaum T, et al. Benign familial neonatal convulsions linked to genetic markers on chromosome 20. Nntwe 1989; 337: 647-648.
17
Lewis TB, Leach RJ, Ward benign familial neonatal new locus on chromosome 670-675.
K et nl. Genetic heterogeneity in convulsions: identification of a 8q. Anr 1 Hum Genef 1993; 53:
18
Liu AW, Delgado-Escueta AV, Serratosa JM et al. Juvenile myoclonic epilepsy locus in chromosome 6p21.2-pll:linkage to convulsions and electroencephalography trait. Am ] Htm Genet 1995; 57: 368-381.
19
Matsuura T, Sutcliffe JS, Fang P et RI. De novo truncating mutations in E6-Al’ ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome. Nature Genet 1997; 15: 74-77.
20
Ottman R, Risch N, Hauser WA et nl. Localization for partial epilepsy to chromosome 1Oq. Nntitre lo: 56-60.
21
22
23
24
25
of a gene Genet 1995;
26
27
28
29
30
Pennacchio LA, Lehesjoki A-E, Stone NE et nl. Mutations in the gene encoding cystatin B in progressive myoclonus epilepsy (EPMI). Science 1996; 271: 1731-1734.
31
Phillips HA, Scheffer IE, Berkovic SF et nl. Localization of a gene for autosomal dominant nocturnal frontal lobe epilepsy to chromosome 20q13.2. Notwe Genet 1995; 10: 117-118.
32
Savukoski M, Kestila M, Williams R et nl. Defined chromosomal assignment of CLN5 demonstrates that at least four genetic loci are involved in the pathogenesis of human ceroid lipofuscinoses. Am 1 Hton Genet 1994; 55: 695701. Serratosa JM, Delgado-Escueta AV, Posada I et nl. The gene for progressive myoclonus epilepsy of the Lafora type maps to chromosome 6q. Hum Mel Genet 1995; 5: 1657-1663. Sharp JD, Wheeler RB, Lake BD et al. Loci for classical and a variant late infantile neuronal ceroid lipofuscinosis map to chromosomes 11~15 and 15q21-23. Hum MO/ Gcnet 1997; 6: 591-596.
33
34
35
Shoffner JM, Bialer MG, Pavlakis SG et al. Mitochondrial encephalomyopathy associated with a single nucleotide pair deletion in the mitochondrial tRNALeu (UUR) gene. Neurology 1990; 45: 286-292. Steinlein OK, Mulley JC, Propping P et al. A missense mutation in the neuronal receptor ct4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. Nature Genet 1995; 11: 201-203. Tahvanainen E, Ranta S, Hirvasniemi A et al. The gene for a recessively inherited human childhood progressive epilepsy with mental retardation maps to the distal short arm of chromosome 8. PNAS 1994; 91: 7267-7270. Verkerk AJMH, Pieretti M, Sutcliffe JS et al. Identification of a gene (EMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 1991; 65: 905-914. Vesa J, Hellsten E, Verkruyse LA et RI. Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis. Nature 1995; 376: 584-587. Wallace RH, Berkovic SF, Howell RA et nl. Suggestion of a major gene for familial febrile convulsions mapping to 8q13-21. J Med Genet 1996; 33: 308-312. Weissbecker KA, Dumer M, Janz D et al. Confirmation of linkage between juvenile myoclonic epilepsy locus and the HLA region on chromosome 6. Am j Med Genef 1991; 38: 32-36. Whitehouse WP, Rees M, Curtis D et nl. Linkage analysis of idiopathic generalised epilepsy and marker loci on chromosome 6p in families of patients with juvenile myoclonic epilepsy: no evidence for an epilepsy locus in the HLA region. Am \ Hum Genet 1993; 53: 652-662. Xu GF, 0 Connell P, Viskochil D et RI. The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell 1990; 62:599408. Zara F, Bianchi A, Avanzini G et nl. Mapping of genes predisposing to idiopathic generalized epilepsy. Hunt Mel Genet 1995; 4: 1201-1207.
Gene table: Epilepsy
Neurology
Mendelian
1:
55-57
(Frances Elmslie)
Disease
Primary
1997;
Mode of inheritance
Gene location
Gene symbol (gene product)
MIM
Key refs
EBNl EBNZ
121200 121201
16,17
epilepsies
Benign familial convulsions
neonatal
AD
2oq13 8q24
Benign familial convulsions
infantile
AD
1%
10
Autosomal dominant frontal lobe epilepsy
nocturnal
AD
2oq13
Partial epilepsy symptoms
auditory
AD
14
AR
8P
EPMR
Unverricht-Lundborg disease (Baltic myoclonus, Mediterranean myoclonus)
AR
21q22
EPMl (Cystatin
Infantile neuronal lipofuscinosis
AR
1~32
AR
llp15
CLNl (palmitoyl protein thioesterase) CLN2
AR
15q21-23
CLNC
AR
16~12
CLN3
204200
4, 11
AR
13q22
CLN5
256731
23
AR
6q23-25
254780
24
Complex
?6p ?8q24
254770 121210
3, 5, 9,18, 32, 33
with
Progressive epilepsy with mental retardation (Northern epilepsy) Progressive epilepsies
CHRNA4 (nAChR a4 subunit)
600513
22,27
600512
20
600143
28
254800
15,21
256730
12,30
204500
25
myoclonic
ceroid
Late infantile neuronal ceroid lipofuscinosis Variant late infantile neuronal ceroid lipofuscinosis Juvenile neuronal ceroid lipofuscinosis Finnish variant neuronal ceroid lipofuscinosis Lafora disease
B)
25
Epilepsy syndromes displaying complex inheritance Juvenile
myoclonic
epilepsy
Idiopathic generalized Febrile convulsions
epilepsy
Complex Complex
EJMl
?8q13-21
35 31
600669
(continued)
Correspondence: logo-3798/97/010055+3
Dr Frances
Elmslie, $18.00
Department
of Clinical
Genetics,
Institute
of Child
Health,
30 Guilford
Street,
0 1997
European
London Society
WC1 N 1EH, UK
of
Paediatric
Neurology
Gene
56
Disease
Mode of inheritance
Gene location
Gene (gene
AD
9q34 16~13
TSCl TSC2
15q13
ANCR (EC-AI’
symbol product)
tab/e:
F Elmslie
MIM
Key
refs
191100
6, 7, 13
Mendelian disorders including epilepsy as part of the phenotype Tuberous
sclerosis
191092
(tuberin) Angelman
AD
syndrome
105830
2, 14, 19
162200
1, 34
309550
29
ubiquitin-protein ligase) Neurofibromatosis
type
AD
1
NFl
17qll
(neurofibromin) Fragile
X-linked
X
FMR-1
xq27
(fragile X mental retardation protein)
Mitochondrial
disorders
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Myoclonic red fibres MIM:
epilepsy (MERRF)
Mendelian
with
inheritance
ragged
Maternal
tRNA-Leu WW
540000
8
Maternal
tRNA-Lys
545000
26
in Man.
References
Barker D, Wright E, Nguyen K et al. Gene for von Reckhnghausen neurofibromatosis is in the pericentromeric region of chromosome 17. Science 1987; 236: 1100-1102. Chan CT, Clayton-Smith J, Cheng XJ ef al. Molecular mechanisms in Angelman syndrome: a survey of 93 patients. 1 Med Genet 1993; 30: 895-902. Dumer M, Sander T, Greenberg DA et nl. Localisation of idiopathic generalised epilepsy on chromosome 6p in families of juvenile myoclonic epilepsy patients. Neurology 1991; 41: 1651-1655. Eiberg H, Gardiner RM, Mohr J. Batten disease (SpielmeyerSjGgren disease) and haptoglobins (HP):indication of linkage and assignment to chromosome 16. C/in Genet 1989; 36: 217218. ElmsIie FV, Williamson MP, Rees M et al. Linkage analysis of juvenile myoclonic epilepsy and microsatellite loci spanning 61 CM of human chromosome 6p in 19 nuclear pedigrees provides no evidence for a susceptibility locus in this region. Am j Hum Genet 1996; 59: 653-663.
8
9
10
11
12
13
European chromosome 16 tuberous sclerosis consortium. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell 2993; 75: 1305-1315.
14
Fryer AE, Chalmers A, Connor JM et al. Evidence that the gene for tuberous sclerosis is on chromosome 9. Lancet 1987; i: 659-661.
15
Goto Y, Nonaka I, Horai S et al. A mutation in the tRNA-leu (UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature 1990; 348: 651-653. Greenberg DA, Delgado-Escueta AV, Widelitz H et al. Juvenile myoclonic epilepsy may be linked to the BF and HLA loci on human chromosome 6. Am 1 Med Genet 1988; 31: 185-192. Guipponi M, Rivier F, Vigevano F et al. Linkage mapping of benign infantile convulsions (BFIC) to chromosome 19q. Hum Mol Gerlet 1997; 6: 473-477. The International Batten Disease Consortium. Isolation of a novel gene underlying Batten Disease, CLN3. Cell 1995; 82: 949-957. Jarvela I, SchIeutker J, Haataja L et al. Infantile form of neuronal ceroid lipofuscinosis (CLNl) maps to the short arm of chromosome 1. Genomics 1991; 9: 170-173. Kandt RS, Haines JL, Smith M et al. Linkage of an important gene locus to a chromosome 16 marker for polycystic kidney disease. Nature Gene1 1992; 2: 3741. Kishino T, Lalande M, Wagstaff J et al. UBE3A/E6-AP mutations cause Angehnan syndrome. Nature Gene1 1997; IS: 70-73. Lehesjoki A-E, Koskiniemi M, Sistonen P, et al. Localisation of a gene for progressive myoclonus epilepsy to chromosome 21q22. PNAS 1991; 88: 3696-3699.
57
Gene table: Epilepsy 16
Leppert M, Anderson VE, Quattlebaum T, et al. Benign familial neonatal convulsions linked to genetic markers on chromosome 20. Nntwe 1989; 337: 647-648.
17
Lewis TB, Leach RJ, Ward benign familial neonatal new locus on chromosome 670-675.
K et nl. Genetic heterogeneity in convulsions: identification of a 8q. Anr 1 Hum Genef 1993; 53:
18
Liu AW, Delgado-Escueta AV, Serratosa JM et al. Juvenile myoclonic epilepsy locus in chromosome 6p21.2-pll:linkage to convulsions and electroencephalography trait. Am ] Htm Genet 1995; 57: 368-381.
19
Matsuura T, Sutcliffe JS, Fang P et RI. De novo truncating mutations in E6-Al’ ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome. Nature Genet 1997; 15: 74-77.
20
Ottman R, Risch N, Hauser WA et nl. Localization for partial epilepsy to chromosome 1Oq. Nntitre lo: 56-60.
21
22
23
24
25
of a gene Genet 1995;
26
27
28
29
30
Pennacchio LA, Lehesjoki A-E, Stone NE et nl. Mutations in the gene encoding cystatin B in progressive myoclonus epilepsy (EPMI). Science 1996; 271: 1731-1734.
31
Phillips HA, Scheffer IE, Berkovic SF et nl. Localization of a gene for autosomal dominant nocturnal frontal lobe epilepsy to chromosome 20q13.2. Notwe Genet 1995; 10: 117-118.
32
Savukoski M, Kestila M, Williams R et nl. Defined chromosomal assignment of CLN5 demonstrates that at least four genetic loci are involved in the pathogenesis of human ceroid lipofuscinoses. Am 1 Hton Genet 1994; 55: 695701. Serratosa JM, Delgado-Escueta AV, Posada I et nl. The gene for progressive myoclonus epilepsy of the Lafora type maps to chromosome 6q. Hum Mel Genet 1995; 5: 1657-1663. Sharp JD, Wheeler RB, Lake BD et al. Loci for classical and a variant late infantile neuronal ceroid lipofuscinosis map to chromosomes 11~15 and 15q21-23. Hum MO/ Gcnet 1997; 6: 591-596.
33
34
35
Shoffner JM, Bialer MG, Pavlakis SG et al. Mitochondrial encephalomyopathy associated with a single nucleotide pair deletion in the mitochondrial tRNALeu (UUR) gene. Neurology 1990; 45: 286-292. Steinlein OK, Mulley JC, Propping P et al. A missense mutation in the neuronal receptor ct4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. Nature Genet 1995; 11: 201-203. Tahvanainen E, Ranta S, Hirvasniemi A et al. The gene for a recessively inherited human childhood progressive epilepsy with mental retardation maps to the distal short arm of chromosome 8. PNAS 1994; 91: 7267-7270. Verkerk AJMH, Pieretti M, Sutcliffe JS et al. Identification of a gene (EMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 1991; 65: 905-914. Vesa J, Hellsten E, Verkruyse LA et RI. Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis. Nature 1995; 376: 584-587. Wallace RH, Berkovic SF, Howell RA et nl. Suggestion of a major gene for familial febrile convulsions mapping to 8q13-21. J Med Genet 1996; 33: 308-312. Weissbecker KA, Dumer M, Janz D et al. Confirmation of linkage between juvenile myoclonic epilepsy locus and the HLA region on chromosome 6. Am j Med Genef 1991; 38: 32-36. Whitehouse WP, Rees M, Curtis D et nl. Linkage analysis of idiopathic generalised epilepsy and marker loci on chromosome 6p in families of patients with juvenile myoclonic epilepsy: no evidence for an epilepsy locus in the HLA region. Am \ Hum Genet 1993; 53: 652-662. Xu GF, 0 Connell P, Viskochil D et RI. The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell 1990; 62:599408. Zara F, Bianchi A, Avanzini G et nl. Mapping of genes predisposing to idiopathic generalized epilepsy. Hunt Mel Genet 1995; 4: 1201-1207.