Publications (21)105.74 Total impact
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Article: Novel Myoclonin1/EFHC1 mutations in Mexican patients with juvenile myoclonic epilepsy.
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ABSTRACT: The purpose of this study was to identify the prevalence of mutations in the Myoclonin1/EFHC1 gene in Mexican patients with juvenile myoclonic epilepsy (JME). We studied forty-one patients at the National Institute of Neurology and Neurosurgery in Mexico City and 100 healthy controls. DNA was extracted from the peripheral venous blood of all participants. The exons of EFHC1 were then amplified and sequenced. We found three new putative mutations, all of which were heterozygous missense mutations located in exon 3. The first identified mutation, 352C>T, produces a R118C change in the protein and cosegregated in the patient's affected father and brother. The second identified mutation, 544C>T, produces a R182L change in the protein and was found in the patient's asymptomatic father. The third identified mutation, 458>A, produces a R153Q change in the protein and was also found in the patient's father. These mutations were not found in controls. The frequency of Myoclonin1/EFHC1 mutations in our sample is 7.3%. Thus, we conclude that mutations in the Myoclonin1/EFHC1 gene are an important cause of JME in Mexican patients.Seizure 06/2012; 21(7):550-4. · 1.80 Impact Factor -
Article: Absence of Multiple Sclerosis and Demyelinating Diseases among Lacandonians, a Pure Amerindian Ethnic Group in Mexico.
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ABSTRACT: Multiple Sclerosis (MS) is a highly polymorphic disease characterized by different neurologic signs and symptoms. In MS, racial and genetic factors may play an important role in the geographic distribution of this disease. Studies have reported the presence of several protective alleles against the development of autoimmune disorders. In the case of MS, however, they help define MS as a complex disease, and confirm the importance of environmental agents as an independent variable not associated with ethnicity. We carried out an on-site epidemiological study to confirm the absence of MS or NMO among Lacandonians, a pure Amerindian ethnic group in Mexico. We administered a structured interview to 5,372 Lacandonians to assess by family background any clinical data consistent with the presence of a prior demyelinating event. Every participating subject underwent a comprehensive neurological examination by a group of three members of the research team with experience in the diagnosis and treatment of demyelinating disorders to detect clinical signs compatible with a demyelinating disease. We did not find any clinical signs compatible with multiple sclerosis among study participants.Multiple sclerosis international. 01/2012; 2012:292631. -
Article: Low frequency of common LRRK2 mutations in Mexican patients with Parkinson's disease.
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ABSTRACT: Mutations in leucine-rich repeat kinase 2 gene (LRRK2) account for as much as 5-6% of familial Parkinson's disease (PD) and 1-2% of sporadic PD. These mutations represent the most frequent cause of autosomal dominant PD, particularly in certain ethnic groups. In this first report concerning LRRK2 mutations in Mexican-mestizos, we screened 319 consecutive PD patients (186 males; 133 females; mean age at onset: 52.4 years) for LRRK2 mutations in exons 31 and 41 and for the mutation in exon 35, which produces the Y1699C substitution. Three (0.94%) patients, two with sporadic PD and one with familial PD (disease mean age at onset, 53.3 years), were heterozygous for LRRK2 mutations. Of these three, two patients had one of two different mutations in exon 31 (R1441G and R1441H, respectively); the other patient carried the G2019S mutation in exon 41. The Y1699C mutation was absent from this PD sample. Four additional subjects, unaffected relatives of one PD patient with a mutation in LRRK2, were subsequently genetically tested. None of the three LRRK2 mutations identified was present in 200 neurologically healthy Mexican control individuals. These findings have important implications for molecular testing of LRRK2 mutations in Mexican PD patients.Neuroscience Letters 11/2010; 485(2):79-82. · 2.11 Impact Factor -
Article: Uptake of genetic testing and long-term tumor surveillance in von Hippel-Lindau disease
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ABSTRACT: Abstract Background von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome caused by germline mutations in the VHL gene. Patients have significant morbidity and mortality secondary to vascular tumors. Disease management is centered on tumor surveillance that allows early detection and treatment. Presymptomatic genetic testing is therefore recommended, including in at-risk children. Methods We tested 17 families (n = 109 individuals) for VHL mutations including 43 children under the age of 18. Personalized genetic counseling was provided pre and post-test and the individuals undergoing presymptomatic testing filled out questionnaires gathering socio-demographic, psychological and psychiatric data. Mutation analysis was performed by direct sequencing of the VHL gene. Mutation-carriers were screened for VHL disease-related tumors and were offered follow-up annual examinations. Results Mutations were identified in 36 patients, 17 of whom were asymptomatic. In the initial screening, we identified at least one tumor in five of 17 previously asymptomatic individuals. At the end of five years, only 38.9% of the mutation-carriers continued participating in our tumor surveillance program. During this time, 14 mutation carriers developed a total of 32 new tumors, three of whom died of complications. Gender, education, income, marital status and religiosity were not found to be associated with adherence to the surveillance protocol. Follow-up adherence was also independent of pre-test depression, severity of disease, or number of affected family members. The only statistically significant predictor of adherence was being symptomatic at the time of testing (OR = 5; 95% CI 1.2 - 20.3; p = 0.02). Pre-test anxiety was more commonly observed in patients that discontinued follow-up (64.7% vs. 35.3%; p = 0.01). Conclusions The high initial uptake rate of genetic testing for VHL disease, including in minors, allowed the discontinuation of unnecessary screening procedures in non mutation-carriers. However, mutation-carriers showed poor adherence to long-term tumor surveillance. Therefore, many of them did not obtain the full benefit of early detection and treatment, which is central to the reduction of morbidity and mortality in VHL disease. Studies designed to improve adherence to vigilance protocols will be necessary to improve treatment and quality of life in patients with hereditary cancer syndromes.BMC Medical Genetics. 01/2010; -
Article: Uptake of genetic testing and long-term tumor surveillance in von Hippel-Lindau disease.
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ABSTRACT: von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome caused by germline mutations in the VHL gene. Patients have significant morbidity and mortality secondary to vascular tumors. Disease management is centered on tumor surveillance that allows early detection and treatment. Presymptomatic genetic testing is therefore recommended, including in at-risk children. We tested 17 families (n = 109 individuals) for VHL mutations including 43 children under the age of 18. Personalized genetic counseling was provided pre and post-test and the individuals undergoing presymptomatic testing filled out questionnaires gathering socio-demographic, psychological and psychiatric data. Mutation analysis was performed by direct sequencing of the VHL gene. Mutation-carriers were screened for VHL disease-related tumors and were offered follow-up annual examinations. Mutations were identified in 36 patients, 17 of whom were asymptomatic. In the initial screening, we identified at least one tumor in five of 17 previously asymptomatic individuals. At the end of five years, only 38.9% of the mutation-carriers continued participating in our tumor surveillance program. During this time, 14 mutation carriers developed a total of 32 new tumors, three of whom died of complications. Gender, education, income, marital status and religiosity were not found to be associated with adherence to the surveillance protocol. Follow-up adherence was also independent of pre-test depression, severity of disease, or number of affected family members. The only statistically significant predictor of adherence was being symptomatic at the time of testing (OR = 5; 95% CI 1.2 - 20.3; p = 0.02). Pre-test anxiety was more commonly observed in patients that discontinued follow-up (64.7% vs. 35.3%; p = 0.01). The high initial uptake rate of genetic testing for VHL disease, including in minors, allowed the discontinuation of unnecessary screening procedures in non mutation-carriers. However, mutation-carriers showed poor adherence to long-term tumor surveillance. Therefore, many of them did not obtain the full benefit of early detection and treatment, which is central to the reduction of morbidity and mortality in VHL disease. Studies designed to improve adherence to vigilance protocols will be necessary to improve treatment and quality of life in patients with hereditary cancer syndromes.BMC Medical Genetics 01/2010; 11:4. · 2.33 Impact Factor -
Article: Presymptomatic diagnosis in Huntington's disease: the Mexican experience.
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ABSTRACT: Huntington's disease (HD) is an autosomal dominant progressive, disabling neurodegenerative disorder, for which there is no effective treatment. Predictive testing (PT) for this illness began in 1986 and by 1993 it became more precise after cloning of the gene and the discovery of a CAG repeat expansion as the underlying cause. The objective of this paper is to illustrate the implementation and results of a PT program in a group of at-risk Mexican individuals with 12 years of follow-up. Our PT program conforms to the guidelines proposed by the International Huntington Association and the HD Working group of the World Federation of Neurology. Seventy-five individuals requested the testing, four of them did not fulfill the inclusion criteria, and five abandoned the program voluntarily before receiving the test results. Therefore, 66 results were delivered to 41 noncarriers and 25 mutation carriers. We did not have any catastrophic event, but 4 individuals with normal results and 11 mutation carriers were depressed. Even if this is a small sample, it is the first report of PT in a Latin-American population in which we have been faced with the same problems referred to in larger series.Genetic Testing and Molecular Biomarkers 10/2009; 13(6):717-20. · 1.11 Impact Factor -
Article: Clinical and genetic characteristics of Mexican Huntington's disease patients.
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ABSTRACT: We report the characteristics of 691 Mexican patients with Huntington's disease (HD). These patients, representing 401 families, constitute the largest series of Mexican HD cases as yet described in the literature. We found the clinical characteristics of these patients to be similar to those of other populations, but we observed a higher frequency of infantile cases, a shorter disease duration and a lower suicide rate. In 626 cases, for which molecular analyses were available, CAG-trinucleotide expansion size ranged from 37-106 repeats. The large number of CAG repeats (19.04 +/- 3.02) in normal alleles and the presence of new mutations suggest that the overall prevalence of HD in the Mexican population could be expected to be within range of, or higher than, that reported for Europeans.Movement Disorders 09/2009; 24(13):2012-5. · 4.51 Impact Factor -
Article: DNA variants in coding region of EFHC1: SNPs do not associate with juvenile myoclonic epilepsy.
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ABSTRACT: Juvenile myoclonic epilepsy (JME) accounts for 3 to 12% of all epilepsies. In 2004, we identified a mutation-harboring Mendelian gene that encodes a protein with one EF-hand motif (EFHC1) in chromosome 6p12. We observed one doubly heterozygous and three heterozygous missense mutations in EFHC1 segregating as an autosomal dominant gene with 21 affected members of six Hispanic JME families from California and Mexico. In 2006, similar and three novel missense mutations were reported in sporadic and familial Caucasian JME from Italy and Austria. In this study, we asked if coding single nucleotide polymorphisms (SNPs) of EFHC1 also contribute as susceptibility alleles to JME with complex genetics. We screened using denaturing high-performance liquid chromatography (DHPLC) and then directly sequenced the 11 exons of EFHC1 in 130 unrelated JME probands, their 352 family members, and seven exons of EFHC1 in 400-614 ethnically matched controls. We carried out case-control association studies between 124 unrelated Hispanic JME probands and 552-614 ethnically matched controls using four SNPs, rs3804506, rs3804505, rs1266787, and rs17851770. We also performed family-based association on SNPs rs3804506 and rs3804505 in 84 complete JME families using the Family-Based Association Test (FBAT) program. We found no statistically significant differences between JME probands and controls in case-control association and no genetic transmission disequilibria in family-based association for the tested SNPs. In addition, we identified four new DNA variants in the coding region of EFHC1. The four coding SNPs, rs3804506, rs3804505, rs1266787, and rs17851770, of EFHC1 may not be susceptibility alleles for JME.Epilepsia 10/2008; 50(5):1184-90. · 3.96 Impact Factor -
Article: Hyperglycosylation and reduced GABA currents of mutated GABRB3 polypeptide in remitting childhood absence epilepsy.
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ABSTRACT: Childhood absence epilepsy (CAE) accounts for 10% to 12% of epilepsy in children under 16 years of age. We screened for mutations in the GABA(A) receptor (GABAR) beta 3 subunit gene (GABRB3) in 48 probands and families with remitting CAE. We found that four out of 48 families (8%) had mutations in GABRB3. One heterozygous missense mutation (P11S) in exon 1a segregated with four CAE-affected persons in one multiplex, two-generation Mexican family. P11S was also found in a singleton from Mexico. Another heterozygous missense mutation (S15F) was present in a singleton from Honduras. An exon 2 heterozygous missense mutation (G32R) was present in two CAE-affected persons and two persons affected with EEG-recorded spike and/or sharp wave in a two-generation Honduran family. All mutations were absent in 630 controls. We studied functions and possible pathogenicity by expressing mutations in HeLa cells with the use of Western blots and an in vitro translation and translocation system. Expression levels did not differ from those of controls, but all mutations showed hyperglycosylation in the in vitro translation and translocation system with canine microsomes. Functional analysis of human GABA(A) receptors (alpha 1 beta 3-v2 gamma 2S, alpha 1 beta 3-v2[P11S]gamma 2S, alpha 1 beta 3-v2[S15F]gamma 2S, and alpha 1 beta 3-v2[G32R]gamma 2S) transiently expressed in HEK293T cells with the use of rapid agonist application showed that each amino acid transversion in the beta 3-v2 subunit (P11S, S15F, and G32R) reduced GABA-evoked current density from whole cells. Mutated beta 3 subunit protein could thus cause absence seizures through a gain in glycosylation of mutated exon 1a and exon 2, affecting maturation and trafficking of GABAR from endoplasmic reticulum to cell surface and resulting in reduced GABA-evoked currents.The American Journal of Human Genetics 07/2008; 82(6):1249-61. · 10.60 Impact Factor -
Article: Anticipation and intergenerational repeat instability in spinocerebellar ataxia type 17.
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ABSTRACT: Spinocerebellar ataxia type 17 (SCA17) is caused by expansion of a CAG/CAA repeat in the TBP gene. Most pathogenic alleles are interrupted and are stably transmitted from parent to offspring without anticipation. We identified three SCA17 families with expansion of uninterrupted alleles, thus greatly increasing the number of known intergenerational transmissions of such alleles. We found that uninterrupted SCA17 alleles are unstable, associated with anticipation, and show a paternal expansion bias that increases with age. Even small increments in repeat length resulted in inordinate increases in anticipation. Anticipation was also associated with childhood presentation. Sequencing of all SCA17 alleles is required for effective genetic counseling.Annals of Neurology 07/2007; 61(6):607-10. · 11.09 Impact Factor -
Article: Distinct distribution of autosomal dominant spinocerebellar ataxia in the Mexican population.
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ABSTRACT: Dominant ataxias show wide geographic variation. We analyzed 108 dominant families and 123 sporadic ataxia patients from Mexico for mutations causing SCA1-3, 6-8, 10, 12, 17 and DRPLA. Only 18.5% of dominant families remained undiagnosed; SCA2 accounted for half (45.4%), followed by SCA10 (13.9%), SCA3 (12%), SCA7 (7.4%), and SCA17 (2.8%). None had SCA1, 6, 8, 12 or DRPLA. Among sporadic cases, 6 had SCA2 (4.9%), and 2 had SCA17 (1.6%). In the SCA2 patients we identified 6 individuals with the rare (CAG)(33) allele, 2 of whom showed early onset ataxia. The distribution of dominant ataxia mutations in Mexicans is distinct from other populations.Movement Disorders 05/2007; 22(7):1050-3. · 4.51 Impact Factor -
Article: Apolipoprotein E epsilon4 allele is associated with Parkinson disease risk in a Mexican Mestizo population.
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ABSTRACT: We investigated the association between apolipoprotein E (APOE) alleles and genotypes and Parkinson disease (PD) in 229 unrelated Mexican Mestizo PD patients and 229 controls. Results showed that both APOE-epsilon4 allele and APOE epsilon4/epsilon3 genotype are associated with PD (OR = 1.736, P = 0.011; OR = 1.688, P = 0.019, respectively). Mean age at onset of PD was not associated to any APOE allele or genotype, but was significantly earlier in familial PD when compared to sporadic cases (P = 0.025).Movement Disorders 03/2007; 22(3):417-20. · 4.51 Impact Factor -
Article: Mutation analyses of genes on 6p12-p11 in patients with juvenile myoclonic epilepsy.
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ABSTRACT: Juvenile myoclonic epilepsy (JME) is a distinct form of idiopathic generalized epilepsy (IGE). One of the candidate regions for human JME has been mapped on chromosome band 6p11-p12 by linkage analyses and is termed EJM1 (MIM 254770). Recently, we reported the reduction of the EJM1 region to 3.5cM that contains 18 genes, the exclusion of three genes (LRRC1, GCLC, KIAA0057) by mutation analyses, and the identification of Myoclonin1/EFHC1 as the EJM1 gene. Here, we describe detailed physical and transcriptome maps of the 3.5cM EJM1 region, and detailed results of mutation analyses for the remained 14 genes (HELO1, GCMA, KIAA0936, FBXO9, GSTA3, GSTA4, PTD011, KIAA0576, LMPB1, IL17F, MCM3, PKHD1, KIAA0105, TFAP2B) in patients with JME. We identified 49 single nucleotide changes in eight genes. Twelve amino acid substitutions occurred in two genes, 11 silent mutations in seven genes, and 26 in the non-coding or intronic regions of seven genes. Twelve amino acid substitutions in the two genes (IL17F, PKHD1) were also observed in healthy control individuals or did not co-segregate with the disease phenotypes in other family members. Thus, the absence of significant and potentially functional mutations in the remaining 14 genes further supports the concept that Myoclonin1/EFHC1 is the EJM1 gene in chromosome 6p12.Neuroscience Letters 10/2006; 405(1-2):126-31. · 2.11 Impact Factor -
Article: Use of oral nutritional supplements in patients with Huntington's disease.
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ABSTRACT: This study assessed the effect of oral nutritional supplements on the nutritional status of patients with Huntington's disease. This was an experimental, longitudinal, prospective study of 30 patients with Huntington's disease. We performed neurologic evaluation and dietary assessment and measured anthropometric indexes and biochemical indicators; in addition, patients were questioned about their weight, appetite, chewing difficulty, and dysphagia. Patients consumed two cans daily of a nutritional supplement that contributed an extra 473 kcal to their diet for a 90-d period. At the study's end, the supplement was suspended and the same variables were reassessed. After 90 d, 68.7% of patients had increased body weight, 68.7% had ideal body weight percentages and body mass indexes, 53.3% had increased midarm circumferences, and 60.0% had increased arm muscle circumferences and body fat percentages; these changes were statistically significant (P < 0.05). The neurologic evaluation subscales and the biochemical indicators did not change significantly. With regard to subjective variables, patients who reported losing weight during the 3 mo before the study did not lose more weight and patients who reported having an increased appetite before the study remained stable during the study. The nutritional intervention stabilized or slightly improved the anthropometric variables assessed; however, no significant change in body mass index occurred in 87% of patients. For the purpose of maintaining an acceptable nutritional status in patients who have Huntington's disease and normal nutritional status, we suggest oral nutritional supplements that contribute an average of 473 kcal/d in addition to a normal diet.Nutrition 09/2005; 21(9):889-94. · 3.03 Impact Factor -
Article: Mutations in EFHC1 cause juvenile myoclonic epilepsy.
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ABSTRACT: Juvenile myoclonic epilepsy (JME) is the most frequent cause of hereditary grand mal seizures. We previously mapped and narrowed a region associated with JME on chromosome 6p12-p11 (EJM1). Here, we describe a new gene in this region, EFHC1, which encodes a protein with an EF-hand motif. Mutation analyses identified five missense mutations in EFHC1 that cosegregated with epilepsy or EEG polyspike wave in affected members of six unrelated families with JME and did not occur in 382 control individuals. Overexpression of EFHC1 in mouse hippocampal primary culture neurons induced apoptosis that was significantly lowered by the mutations. Apoptosis was specifically suppressed by SNX-482, an antagonist of R-type voltage-dependent Ca(2+) channel (Ca(v)2.3). EFHC1 and Ca(v)2.3 immunomaterials overlapped in mouse brain, and EFHC1 coimmunoprecipitated with the Ca(v)2.3 C terminus. In patch-clamp analysis, EFHC1 specifically increased R-type Ca(2+) currents that were reversed by the mutations associated with JME.Nature Genetics 09/2004; 36(8):842-9. · 35.53 Impact Factor -
Article: Assessment of the nutrition status of patients with Huntington's disease.
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ABSTRACT: The purpose of the present study was to compare the nutrition status of patients with Huntington's disease (HD) with that of control subjects by analyzing anthropometric and biochemical indicators, energy, and macronutrient intake and to determine which indicators are most altered in HD patients. We assessed the nutrition status of 25 HD patients and 25 age- and sex-matched controls by measuring anthropometric and biochemical indicators. Food intake data were obtained by the 3-d record method to assess mean daily energy and macronutrient intake. We studied variables reported by the patients such as increased or decreased appetite, mastication difficulties, and solid food and liquid food dysphagia. A neurologist assessed the clinical features of HD patients by using the Unified Huntington's Disease Rating Scale. HD patients showed significantly lower anthropometric variables but significantly higher kilocalorie intake. Among the subjective variables analyzed, patient-referred weight loss, increased appetite, mastication, and solid food dysphagia were significantly more frequent in HD patients than in controls. We also found relations between motor disability and some anthropometric parameters in HD patients. In particular, we found a significant correlation between total motor disability score and body mass index and arm muscle circumference (r = -0.464 and -0.445, respectively; P < 0.05) and with percentage of body fat (r = -0.496, P = 0.012). It is of the utmost importance to identify nutritional alterations in HD patients and to find strategies to cover their kilocalorie and nutrient requirements to improve their quality of life.Nutrition 02/2004; 20(2):192-6. · 3.03 Impact Factor -
Article: Olfactory dysfunction in hereditary ataxia and basal ganglia disorders.
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ABSTRACT: In the present study the olfactory system of hereditary ataxia patients was tested using the smell identification test. Two previous findings suggested a possible olfactory impairment in these patients. First, an olfactory dysfunction has been found in different neurodegenerative diseases, and second, human functional imaging has shown cerebellar activation during olfaction. As an initial approach to determine if cerebellar ataxia impairs the olfactory process, cerebellar ataxia patients, along with basal ganglia patients, were tested. The results show an olfactory deficit in both basal ganglia and hereditary ataxia patients. Further exploration of the olfactory capacities in hereditary ataxia is necessary to elucidate the specific nature of the deficits.Neuroreport 08/2003; 14(10):1339-41. · 1.66 Impact Factor -
Article: Recent developments in the quest for myoclonic epilepsy genes.
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ABSTRACT: Understanding the latest advances in the molecular genetics of the epilepsies is important, as it provides a basis for comprehending the new practice of epileptology. Epilepsies have traditionally been classified and subtyped on the basis of clinical and neurophysiologic concepts. However, the complexity and variability of phenotypes and overlapping clinical features limit the resolution of phenotype-based classification and confound epilepsy nosology. Identification of tightly linked epilepsy DNA markers and discovery of epilepsy-causing mutations provide a basis for refining the classification of epilepsies. Recent discoveries regarding the genetics surrounding certain epilepsy types (including Lafora's progressive myoclonic epilepsy, the severe myoclonic epilepsy of infancy of Dravet, and idiopathic generalized epilepsies) may be the beginning of a better understanding of how rare Mendelian epilepsy genes and their genetic architecture can explain some complexities of the common epilepsies.Epilepsia 02/2003; 44 Suppl 11:13-26. · 3.96 Impact Factor -
Article: Juvenile myoclonic epilepsy: linkage to chromosome 6p12 in Mexico families.
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ABSTRACT: Juvenile myoclonic epilepsy is a common subtype of idiopathic epilepsy accounting for 4-11% of all epilepsies. We reported previously significant evidence of linkage between chromosome 6p12-11 microsatellites and the clinical epilepsy and EEG traits of JME families from Belize and Los Angeles. To narrow the JME region, we ascertained and genotyped 31 new JME families from Mexico using a later generation of Généthon microsatellites. Two point linkage analyses obtained significant Z(max) values of 3.70 for D6S1573 and 2.65 for D6S1714 at theta(m = f) = 0.10, and 3.49 for D6S465, 2.11 for D6S1960 at theta(m = f) = 0.05 assuming autosomal dominant inheritance with 70% age-dependent penetrance. Multipoint LOD score curve peaked at 4.21 for D6S1573. Haplotype and recombination analysis reduced the JME region to 3.5 cM flanked by D6S272 and D6S1573. These results provide confirmatory evidence that a major susceptibility gene for JME exists in chromosome 6p12 in Spanish-Amerinds of Mexico.American Journal of Medical Genetics 01/2003; 113(3):268-74. -
Article: Identification and mutational analysis of candidate genes for juvenile myoclonic epilepsy on 6p11-p12: LRRC1, GCLC, KIAA0057 and CLIC5.
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ABSTRACT: Juvenile myoclonic epilepsy (JME) is one of the most frequent hereditary epilepsies characterized by myoclonic and tonic-clonic convulsions beginning at 8-20 years of age. Genetic studies have revealed four major chromosomal loci on 6p21.3, 6p11-12, 6q24, and 15q14 as candidate regions harboring genes responsible for JME. Previously we reported the region on 6p11-p12 (EJM1), and here we report the identification and mutational analysis of candidate genes for EJM1. One of those is a leucine-rich repeat-containing 1 (LRRC1) gene that is composed of 14 exons and codes for 524 amino acid residues. In Northern analysis, 7 kb transcripts of LRRC1 gene were detected in multiple tissues, most strongly, in heart, lung, and kidney. Mutation analysis of LRRC1 gene in 20 JME patients from ten families revealed one nucleotide substitution that lead to amino acid exchange (c.577 A>G; Ile193Val). This variation, however, did not co-segregate with the disease phenotype. We further performed mutational analyses of CLIC5, KIAA0057 and GCLC genes in or flank to the EJM1 region. These analyses did not provide any evidences that these genes are responsible for the JME phenotype, and suggested that these may not be the EJM1 gene.Epilepsy Research 08/2002; 50(3):265-75. · 2.29 Impact Factor
Top co-authors
Top Journals
- Movement Disorders (2)
- Nutrition (2)
- Epilepsia (1)
- American Journal of Medical Genetics (1)
- Neuroscience Letters (1)
Institutions
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2007–2010
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Instituto Nacional de Neurología y Neurocirugía
Tlalpan, The Federal District, Mexico -
Metropolitan Autonomous University
Mexico City, The Federal District, Mexico
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2003–2008
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University of California, Los Angeles
- Department of Molecular and Medical Pharmacology
Los Angeles, CA, USA
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