Mutations in the gene encoding cystatin B in progressive myoclonus epilepsy (EPM1)

Science

Volumn 271, Issue 5256, 1996, Pages 1731-1734

  Pennacchio, Len A ^a,b   Lehesjoki, Anna Elina ^c   Stone, Nancy E ^a   Willour, Virginia L ^a   Virtaneva, Kimmo ^c   Miao, Jinmin ^c   D'Amato, Elena ^c   Ramirez, Lucia ^a   Faham, Malek ^a   Koskiniemi, Marjaleena ^c   Warrington, Janet A ^a   Norio, Reijo ^d   De La Chapelle, Albert ^c   Cox, David R ^a   Myers, Richard M ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b STANFORD UNIVERSITY   (United States)

^c UNIVERSITY OF HELSINKI   (Finland)

^d Finnish Pop and Fam Welf Fed ^*  (Finland)

Author keywords

[No Author keywords available]

Indexed keywords

CYSTATIN; MESSENGER RNA;

ARTICLE; AUTOSOMAL RECESSIVE INHERITANCE; CHROMOSOME 21Q; CONTROLLED STUDY; FEMALE; GENE LOCATION; GENE MUTATION; HUMAN; HUMAN CELL; MAJOR CLINICAL STUDY; MALE; MYOCLONUS EPILEPSY; PRIORITY JOURNAL; STOP CODON;

EID: 13344269666     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.271.5256.1731     Document Type: Article

References (39)

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28. Total RNA and DNA were extracted from cultured cells with the TRIZOL reagent (BRL. Gaithersburg, MD). Northern blot hybridization was in 5x SSPE. 10x Denhardt's solution, 100 μg/ml of salmon sperm DNA, 50% formamide, and 2% SDS at 42°C for 18 hours. Filters were washed with 2x saline sodium citrate (SSC) at room temperature for 30 min and in 0.1 x SSC at 60°C for 30 min.
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30. The GenBank number for the genomic sequence determined here is U46692. Abbreviations for the amino acids residues are A, Ala; C, Cys, D, Asp; E. Glu, F, Phe; G, Gly, H, His; I, Ile; K, Lys: L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser, T, Thr; V, Val; W, Trp; Y, Tyr; and asterisk, stop codon [A Ritonja, W Machlerdt, A. J Barren, Biochem. Biophys Res Commun 131, 1187 (1985)]. The Gen-Bank number for the cDNA sequence, deposited by K. S. Bhat, is L03558.
31. The gene encoding cystatin B was amplified by PCR in two overlapping segments from genomic DNA of affected individuals from four families These included a 5′ segment with oligonucleotide primers pF2 and 51814R1 and a 3′ segment with primers F11 and R1 (pF2. 5′-CTCCGACTGCCCCTTCCCTAT-3′; 51814R1: 5′-GAGACACAGGGAAA-GTTGCCATCT-3′, F11. 5′-CCACCGTACCCAGCTGGAACTGT-3′; and R1. 5′-CGGAGGATGACTTTGTCAGTCTTC-3′) These primers were used for PCR amplification and for sequencing. The following primers were also used for sequencing F3 5′-TAAGGCCGTGTCATTCAAGAGCCA-3′; F5. 5′-CGCCGAGACCCAGCACATC-3′; and R10- 5′-TCTTAGCTCCCCAGAAGCCCTAGT-3′ The PCR assay for the 5′ segment of the gene included 10% dimethyl sulfoxide and 50% deaza-deoxyguanosine triphosphate and the following cycling conditions initial incubation at 95°C for 5 min followed by 30 cycles of 30 s a; 95°C, 30 s at 65°C, and 2 min at 72°C, with a final incubation for 10 min at 72°C- Conditions for amplifying the 3′ segment of the gene included an initial incubation at 94°C for 5 min followed by 30 cycles for 30 s at 94°C, 30 s at 60°C, and 2 min at 72°C, with a final incubation for 10 min at 72°C. PCR products were purified with a Centricon-100 concentrator (Amicon. Beverly, MA) and sequenced directly with cycle sequencing with SequiTherm DNA polymerase (Epicentre, Madison WI) or cloned into a plasmid vector Cloned products were manually sequenced with Sequenase (U.S Biochemicals. Cleveland, OH). The sequencing reaction products were separated on 6% polyacrylamide gels and visualized by autoradiography
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34. The 3′ spite site mutation was screened in the general population in 95 unrelated Americans (190 chro mosomes). 90% of whom were of European ancestry and 10% of whom were of other ethnic backgrounds The stop codon mutation was screened in 70 Finnish EPM i carrier parents All 70 of these individuals contained the common ancestral haplo-type around the EPM1 locus on one of their chromosomes To distinguish mutations from polymorphisms we considered only the nonancestral haplo-type chromosome of these 70 individuals DMA from these individuals was amplified by PCR, and the products were directly sequenced wth the AmpliCycle sequencing kit (Perkin-Elmer)
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39. We thank the families with EPM1 for contributing to this study. C lannicola C. Prange, D Vollrath. J Kere, and members of the Myers and Cox laboratories and the Stanford Human Genome Center for discussions and support A-L Träskelin and R Tolvanen for technical assistance, and R Eldridge and B J Wilder for providing patient samples from the American family This work was supported by NIH grants HD-24610 and P50 HG-00206 (to R.M.M and D R C). postdoctoral grant NIH IF 32GM17502 (to J A W). NIH grant NS31831 (to A.d I.C.) the Academy of Finland and ths Sigrid Juselius Foundation (to A d I C. and A - E.L), and the Epilepsy Research Foundation of Finland (to A -E L.) Part of this study was done at the Folkhalsan Institute of Genetics (Helsinki)