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Familial adult myoclonic epilepsy type 1 SAMD12 TTTCA repeat expansion arose 17,000 years ago and is present in Sri Lankan and Indian families.

ABSTRACT: Familial adult myoclonic epilepsy 1 (FAME1), first recognised in Japanese families, was recently shown to be caused by a TTTCA repeat insertion in intron 4 of SAMD12 on chromosome 8. We performed whole genome sequencing on two families with FAME, one of Sri Lankan origin and the other of Indian origin, and identified a TTTCA repeat insertion in SAMD12 in both families. Haplotype analysis revealed that both families shared the same core ancestral haplotype reported in Japanese and Chinese families with FAME1. Mutation dating, based on the length of shared haplotypes, estimated the age of the ancestral haplotype to be ~670 generations, or 17,000 years old. Our data extend the geographic range of this repeat expansion to Southern Asia and potentially implicate an even broader regional distribution given the age of the variant. This finding suggests patients of Asian ancestry with suspected FAME should be screened for the SAMD12 TTTCA expansion.

SUBMITTER: Bennett MF

PROVIDER: S-EPMC7316749 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Familial adult myoclonic epilepsy type 1 SAMD12 TTTCA repeat expansion arose 17,000 years ago and is present in Sri Lankan and Indian families.

Bennett Mark F MF Oliver Karen L KL Regan Brigid M BM Bellows Susannah T ST Schneider Amy L AL Rafehi Haloom H Sikta Neblina N Crompton Douglas E DE Coleman Matthew M Hildebrand Michael S MS Corbett Mark A MA Kroes Thessa T Gecz Jozef J Scheffer Ingrid E IE Berkovic Samuel F SF Bahlo Melanie M

European journal of human genetics : EJHG 20200316 7

Familial adult myoclonic epilepsy 1 (FAME1), first recognised in Japanese families, was recently shown to be caused by a TTTCA repeat insertion in intron 4 of SAMD12 on chromosome 8. We performed whole genome sequencing on two families with FAME, one of Sri Lankan origin and the other of Indian origin, and identified a TTTCA repeat insertion in SAMD12 in both families. Haplotype analysis revealed that both families shared the same core ancestral haplotype reported in Japanese and Chinese familie ...[more]

PMID: 32203200

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Project description:BackgroundThe western Russell's viper (Daboia russelii) is widely distributed in South Asia, and geographical venom variation is anticipated among distant populations. Antivenoms used for Russell's viper envenomation are, however, raised typically against snakes from Southern India. The present study investigated and compared the venom proteomes of D. russelii from Sri Lanka (DrSL) and India (DrI), the immunorecognition of Indian VINS Polyvalent Antivenom (VPAV) and its efficacy in neutralizing the venom toxicity.MethodsThe venoms of DrSL and DrI were decomplexed with C18 high-performance liquid chromatography and SDS-polyacrylamide gel electrophoresis under reducing conditions. The proteins fractionated were identified through nano-ESI-liquid chromatography-tandem mass spectrometry (LCMS/MS). The immunological studies were conducted with enzyme-linked immunosorbent assay. The neutralization of the venom procoagulant effect was evaluated in citrated human plasma. The neutralization of the venom lethality was assessed in vivo in mice adopting the WHO protocol.ResultsDrSL and DrI venom proteomes showed comparable major protein families, with phospholipases A2 (PLA2) being the most abundant (> 60% of total venom proteins) and diverse (six protein forms identified). Both venoms were highly procoagulant and lethal (intravenous median lethal dose in mice, LD50 = 0.24 and 0.32 µg/g, for DrSL and DrI, respectively), while lacking hemorrhagic and anticoagulant activities. VPAV was immunoreactive toward DrSL and DrI venoms, indicating conserved protein antigenicity in the venoms. The high molecular weight venom proteins were, however, more effectively immunorecognized than small ones. VPAV was able to neutralize the coagulopathic and lethal effects of the venoms moderately.ConclusionConsidering that a large amount of venom can be injected by Russell's viper during envenomation, the potency of antivenom can be further improved for optimal neutralization and effective treatment. Region-specific venoms and key toxins may be incorporated into the immunization procedure during antivenom production.

Project description:BackgroundThere have been conflicting findings on the effect of body mass index (BMI) on lung functions in children. Therefore, we studied the relationship between spirometry parameters and BMI among healthy Sri Lankan school children aged 5-7 years.MethodsA cross-sectional study was conducted among 296 school children (5-7-year-old) without apparent lung disease. Recruitment was done with stratified random sampling. Spirometry parameters, FEV1, FVC, PEFR, and FEV1/FVC ratio were determined. The acceptable and reproducible spirometry recordings were included in the analysis. Simple and multivariate linear regression analysis examined possible associations of lung function parameters with BMI, socio-demographic variables and indoor risk factors. Also, the mediator effect of gender on lung function through BMI was explored.ResultsThe participants' mean age (SD) was 6.4 (0.65) years. One-third were thin/severely thin (37%). A statistically significant difference in FVC (p = 0.001) and FEV1 (p = 0.001) was observed between BMI groups (obesity/overweight, normal, and thinness). Yet, PEFR or FEV1/FVC did not significantly differ among BMI groups (p = 0.23 and p = 0.84). Multivariate regression analysis showed that FEV1 and FVC were significantly associated with BMI, child's age, gender, family income, father's education, having a pet, and exposure to mosquito coil smoke. Interaction between gender and BMI for lung functions was not significant. The thin children had significantly lower FVC (OR: -0.04, 95%CI: -0.077, -0.012, p = 0.008) and FEV1 (OR: -0.04, 95%CI: -0.075, -0.014, p = 0.004) than normal/overweight/obese children. Family income demonstrated the greatest effect on lung functions; FVC and FEV1 were 0.25L and 0.23L smaller in low-income than the high-income families.ConclusionLower lung function parameters (FVC and FEV1) are associated with thinness than normal/overweight/obese dimensions among children without apparent lung disease. It informs that appropriate nutritional intervention may play a role in improving respiratory health.

Dataset Information

Familial adult myoclonic epilepsy type 1 SAMD12 TTTCA repeat expansion arose 17,000 years ago and is present in Sri Lankan and Indian families.

Publications

Familial adult myoclonic epilepsy type 1 SAMD12 TTTCA repeat expansion arose 17,000 years ago and is present in Sri Lankan and Indian families.

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