Whole-Genome Sequencing for Optimized Patient Management

被引：192

作者：

Bainbridge, Matthew N. ^{[1
,2
]}

Wiszniewski, Wojciech ^{[3
]}

Murdock, David R. ^{[1
]}

Friedman, Jennifer ^{[4
,5
,6
]}

Gonzaga-Jauregui, Claudia ^{[3
]}

Newsham, Irene ^{[1
]}

Reid, Jeffrey G. ^{[1
]}

Fink, John K. ^{[7
,8
]}

Morgan, Margaret B. ^{[1
]}

Gingras, Marie-Claude ^{[1
]}

Muzny, Donna M. ^{[1
]}

Hoang, Linh D. ^{[9
]}

Yousaf, Shahed ^{[9
]}

Lupski, James R. ^{[1
,3
,10
,11
]}

Gibbs, Richard A. ^{[1
,3
]}

机构：

[1] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

[2] Baylor Coll Med, Dept Struct & Computat Biol & Mol Biophys, Houston, TX 77030 USA

[3] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[4] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92093 USA

[5] Univ Calif San Diego, Dept Pediat, San Diego, CA 92093 USA

[6] Rady Childrens Hosp, San Diego, CA 92123 USA

[7] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA

[8] Ann Arbor Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Ann Arbor, MI 48105 USA

[9] Life Technol, Carlsbad, CA 92008 USA

[10] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA

[11] Texas Childrens Hosp, Houston, TX 77030 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2011年 / 3卷 / 87期

基金：

加拿大自然科学与工程研究理事会;

关键词：

DOPA-RESPONSIVE DYSTONIA; SEPIAPTERIN REDUCTASE DEFICIENCY; PROGRESSIVE DYSTONIA; DIURNAL-VARIATION; DIAGNOSIS; GENETICS; DATABASE;

D O I：

10.1126/scitranslmed.3002243

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Whole-genome sequencing of patient DNA can facilitate diagnosis of a disease, but its potential for guiding treatment has been under-realized. We interrogated the complete genome sequences of a 14-year-old fraternal twin pair diagnosed with dopa (3,4-dihydroxyphenylalanine)-responsive dystonia (DRD; Mendelian Inheritance in Man #128230). DRD is a genetically heterogeneous and clinically complex movement disorder that is usually treated with L-dopa, a precursor of the neurotransmitter dopamine. Whole-genome sequencing identified compound heterozygous mutations in the SPR gene encoding sepiapterin reductase. Disruption of SPR causes a decrease in tetrahydrobiopterin, a cofactor required for the hydroxylase enzymes that synthesize the neuro-transmitters dopamine and serotonin. Supplementation of L-dopa therapy with 5-hydroxytryptophan, a serotonin precursor, resulted in clinical improvements in both twins.

引用

页数：6

共 30 条

[1] Classification and genetics of dystonia [J].

Aguiar, PMD ;

Ozelius, LJ .

LANCET NEUROLOGY, 2002, 1 (05) :316-325

[2] A map of human genome variation from population-scale sequencing [J].

Altshuler, David ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Collins, Francis S. ;

De la Vega, Francisco M. ;

Donnelly, Peter ;

Egholm, Michael ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Knoppers, Bartha M. ;

Lander, Eric S. ;

Lehrach, Hans ;

Mardis, Elaine R. ;

McVean, Gil A. ;

Nickerson, DebbieA. ;

Peltonen, Leena ;

Schafer, Alan J. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Deiros, David ;

Metzker, Mike ;

Muzny, Donna ;

Reid, Jeff ;

Wheeler, David ;

Wang, Jun ;

Li, Jingxiang ;

Jian, Min ;

Li, Guoqing ;

Li, Ruiqiang ;

Liang, Huiqing ;

Tian, Geng ;

Wang, Bo ;

Wang, Jian ;

Wang, Wei ;

Yang, Huanming ;

Zhang, Xiuqing ;

Zheng, Huisong ;

Lander, Eric S. ;

Altshuler, David L. ;

Ambrogio, Lauren ;

Bloom, Toby ;

Cibulskis, Kristian ;

Fennell, Tim J. ;

Gabriel, Stacey B. .

NATURE, 2010, 467 (7319) :1061-1073

[3] A Rare Novel Deletion of the Tyrosine Hydroxylase Gene in Parkinson Disease [J].

Bademci, Gueney ;

Edwards, Todd L. ;

Torres, Andre L. ;

Scott, William K. ;

Zuechner, Stephan ;

Martin, Eden R. ;

Vance, Jeffery M. ;

Wang, Liyong .

HUMAN MUTATION, 2010, 31 (10) :E1767-E1771

[4] International database of tetrahydrobiopterin deficiencies [J].

Blau, N ;

Barnes, I ;

Dhondt, JL .

JOURNAL OF INHERITED METABOLIC DISEASE, 1996, 19 (01) :8-14

[5] The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003 [J].

Boeckmann, B ;

Bairoch, A ;

Apweiler, R ;

Blatter, MC ;

Estreicher, A ;

Gasteiger, E ;

Martin, MJ ;

Michoud, K ;

O'Donovan, C ;

Phan, I ;

Pilbout, S ;

Schneider, M .

NUCLEIC ACIDS RESEARCH, 2003, 31 (01) :365-370

[6] Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin-dependent monoamine-neurotransmitter deficiency without hyperphenylalaninemia [J].

Bonafé, L ;

Thöny, B ;

Penzien, JM ;

Czarnecki, B ;

Blau, N .

AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 69 (02) :269-277

[7] Genetic diagnosis by whole exome capture and massively parallel DNA sequencing [J].

Choi, Murim ;

Scholl, Ute I. ;

Ji, Weizhen ;

Liu, Tiewen ;

Tikhonova, Irina R. ;

Zumbo, Paul ;

Nayir, Ahmet ;

Bakkaloglu, Aysin ;

Ozen, Seza ;

Sanjad, Sami ;

Nelson-Williams, Carol ;

Farhi, Anita ;

Mane, Shrikant ;

Lifton, Richard P. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (45) :19096-19101

[8] Exhaustive analysis of BH4 and dopamine biosynthesis genes in patients with Dopa-responsive dystonia [J].

Clot, Fabienne ;

Grabli, David ;

Cazeneuve, Cecile ;

Roze, Emmanuel ;

Castelnau, Pierre ;

Chabrol, Brigitte ;

Landrieu, Pierre ;

Nguyen, Karine ;

Ponsot, Gerard ;

Abada, Myriem ;

Doummar, Diane ;

Damier, Philippe ;

Gil, Roger ;

Thobois, Stephane ;

Ward, Alana J. ;

Hutchinson, Michael ;

Toutain, Annick ;

Picard, Fabienne ;

Camuzat, Agnes ;

Fedirko, Estelle ;

San, Chankannira ;

Bouteiller, Delphine ;

LeGuern, Eric ;

Durr, Alexandra ;

Vidailhet, Marie ;

Brice, Alexis .

BRAIN, 2009, 132 :1753-1763

[9] Sepiapterin reductase deficiency:: Clinical presentation and evaluation of long-term therapy [J].

Echenne, Bernard ;

Roubertie, Agathe ;

Assmann, Birgit ;

Lutz, Thomas ;

Penzien, Johann M. ;

Thoeny, Beat ;

Blau, Nenad ;

Hoffmann, Georg F. .

PEDIATRIC NEUROLOGY, 2006, 35 (05) :308-313

[10] CLINICAL AND GENETIC-ANALYSIS OF PROGRESSIVE DYSTONIA WITH DIURNAL-VARIATION [J].

FINK, JK ;

RAVIN, PD ;

FILLINGKATZ, M ;

ARGOFF, CE ;

HALLETT, M .

ARCHIVES OF NEUROLOGY, 1991, 48 (09) :908-911

← 1 2 3 →