Dystonia (DYT) genetic loci

European Journal of Paediatric Neurology (2005) 9, 367–370

www.elsevier.com/locate/ejpn

GENE TABLE

Dystonia (DYT) genetic loci Roongroj Bhidayasiria,b,*, Stefan-M. Pulstc a

Department of Neurology, Reed Neurological Research Institute, UCLA Medical Center, Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095, USA b Movement Disorders Group, Division of Neurology, Chulalongkorn University, Thailand c Division of Neurology, Cedars-Sinai Medical Center, Departments of Medicine & Neurobiology, UCLA Los Angeles, USA Received 23 February 2005

Table 1

Dystonia (DYT) genetic loci

Designation (OMIM)

Age at onset

Clinical features

Inheritance

Chromosome

Gene/ mutation

Key references

DYT1 (128100), Oppenheim’s dystonia DYT2 (224500)

Mean age 12.5, !28 years in most cases

Early limb onset, usually generalized

AD

9q34

TorsinA

Ozelius et al.1,2, Kramer et al.3

Early onset

AR

–

–

Marsden et al.4, Khan et al.5

DYT3 (314250), Xlinked dystonia parkinsonism, Lubag

Mean 35 years, adult-onset

XR

Xq13.1

–

Kupke et al.6,7, Wilhelmsen et al.8, Nolte et al.9

DYT4 (128101), “Non- DYT1” PTD

13–37 years

Early onset, generalized or segmental dystonia Individuals from Phillipines, male, generalized dystonia, parkinsonism Single Australian family, whispering dysphonia and torticollis

AD

–

–

Ahmad et al.10

* Corresponding author. Tel.: C1 310 206 9799; fax: C1 310 202 0657. E-mail address: [email protected] (R. Bhidayasiri).

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368

R. Bhidayasiri, S.-M. Pulst

Table 1 (continued) Designation (OMIM)

Age at onset

Clinical features

Inheritance

Chromosome

Gene/ mutation

Key references

DYT5a (128230), DRD, Segawa’s disease

Childhood

AD

14q22.1–q22.2

GCH1

Ichinose et al.11, Nygaard et al.12

DYT5b (605407), DRD

Infant

Usually limbonset, dramatic response to levodopa Infantile parkinsonism

AR

11p

TH

DYT6 (602629)

Mean 19 years

AD

8p21–p22

–

DYT7 (602124)

28–70 years

AD

18p

–

Leube et al.17–19

DYT8 (118800), Paroxysmal dystonic choreoathetosis (PDC) DYT9 (601042) Paroxysmal choreoathetosis with episodic ataxia and spasticity DYT10, (128200) Paroxysmal kinesogenic choreoathetosis

Variable, early childhood, adolescence

Two Mennonite families with craniocervical or limb onset Large German family with late-onset craniocervical dystonia Attacks of dystonia, chorea, and athetosis

Ludecke et al.13, Knappskog et al.14 Almasy et al.15, Muller et al.16

AD

2q33–q35

Myofibrillogenesis regulator 1

Fouad et al.20 Fink et al.21, Rainier et al.22

2–15 years

Episodic choreoathetosis, ataxia, spasticity

AD

1p13.3–p21

–

Auburger et al.23

6–16 years

AD

16p11.2–q12.1

–

Tomita et al.24

DYT11 (159900), Myoclonusdystonia (M-D) DYT12 (128235), Rapid-onset dystonia-parkinsonism (RDP) DYT13 (607671)

Variable

Paroxysmal choreoathetosis, precipitated by sudden movements Myoclonus, dystonia, alcohol responsive Acute or subacute onset of dystonia and parkinsonism

AD

7q21, 11q23

3-sarcoglycan

Zimprich et al.25, Nygaard et al.26

AD

19q13

ATP1A3

Kramer et al.27, de Carvalho et al.28

AD

1p36.13–36.32

–

Bentivoglio et al.29, Valente et al.30

DYT14 (607195)

Childhood

Single Italian family with cervical dystonia and segemental dystonia Dopa responsive dystonia

AD

14q13

–

Grotzsch et al.31

Childhood, adolescent

5 years to adults

Dystonia (DYT) genetic loci Table 1

369

(continued)

Designation (OMIM)

Age at onset

Clinical features

Inheritance

Chromosome

Gene/ mutation

Key references

DYT15 (607488)

Childhood to adolescent

Single Canadian family with alcoholresponsive myoclonic dystonia, limb dystonia

AD

18p11

–

Grimes et al.32, 33

AD, Autosomal dominant; AR, Autosomal recessive; DRD, Dopa responsive dystonia; GCH1, GTP cyclohydrolase I; TH, Tyrosine hydroxylase.

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15. Almasy L, Bressman SB, Raymond D, et al. Idiopathic torsion dystonia linked to chromosome 8 in two Mennonite families. Ann Neurol 1997;42:670–3. 16. Muller U, Steinberger D, Nemeth AH. Clinical and molecular genetics of primary dystonias. Neurogenetics 1998;1: 165–77. 17. Leube B, Rudnicki D, Ratzlaff T, Kessler KR, Benecke R, Auburger G. Idiopathic torsion dystonia: assignment of a gene to chromosome 18p in a German family with adult onset, autosomal dominant inheritance and purely focal distribution. Hum Mol Genet 1996;5:1673–7. 18. Leube B, Hendgen T, Kessler KR, Knapp M, Benecke R, Auburger G. Evidence for DYT7 being a common cause of cervical dystonia (torticollis) in central Europe. Am J Med Genet 1997;74:529–32. 19. Leube B, Hendgen T, Kessler KR, Knapp M, Benecke R, Auburger G. Sporadic focal dystonia in northwest Germany: molecular basis on chromosome 18p. Ann Neurol 1997;42: 111–4. 20. Fouad GT, Servidei S, Durcan S, Bertini E, Ptacek LJ. A gene for familial paroxysmal dyskinesia (FPD1) maps to chromosome 2q. Am J Hum Genet 1996;59:135–9. 21. Fink JK, Rainer S, Wilkowski J, et al. Paroxysmal dystonic choreoathetosis: tight linkage to chromosome 2q. Am J Hum Genet 1996;59:140–5. 22. Rainier S, Thomas D, Tokarz D, et al. Myofibrillogenesis regulator 1 gene mutations cause paroxysmal dystonic choreoathetosis. Arch Neurol 2004;61:1025–9. 23. Auburger G, Ratzlaff T, Lunkes A, et al. A gene for autosomal dominant paroxysmal choreoathetosis/spasticity (CSE) maps to the vicinity of a potassium channel gene cluster on chromosome 1p, probably within 2 cM between D1S443 and D1S197. Genomics 1996;31:90–4. 24. Tomita H, Nagamitsu S, Wakui K, et al. Paroxysmal kinesigenic choreoathetosis locus maps to chromosome 16p11.2-q12.1. Am J Hum Genet 1999;65:1688–97. 25. Zimprich A, Grabowski M, Asmus F, et al. Mutations in the gene encoding nohybreake-sarcoglycan cause myoclonusdystonia syndrome. Nat Genet 2001;29:66–9. 26. Nygaard TG, Raymond D, Chen C, et al. Localization of a gene for myoclonus-dystonia to chromosome 7q21–q31. Ann Neurol 1999;46:794–8. 27. Kramer PL, Mineta M, Klein C, et al. Rapid-onset dystoniaParkinsonism: linkage to chromosome 19q13. Ann Neurol 1999;46:176–82. 28. de Carvalho Aguiar P, Sweadner KJ, Penniston JT, et al. Mutations in the NaC/KC-ATPase alpha3 gene ATP1A3 are

370 associated with rapid-onset dystonia parkinsonism. Neuron 2004;43:169–75. 29. Bentivoglio AR, Del Grosso N, Albanese A, Cassetta E, Tonali P, Frontali M. Non-DYT1 dystonia in a large Italian family. J Neurol Neurosurg Psychiatr 1997;62:357–60. 30. Valente EM, Bentivoglio AR, Cassetta E, et al. DYT13, a novel primary torsion dystonia locus, maps to chromosome 1p36.13-36.32 in an Italian family with cranial–cervical or upper limb onset. Ann Neurol 2001;49:362–6.

R. Bhidayasiri, S.-M. Pulst 31. Grotzsch H, Pizzolato GP, Ghika J, et al. Neuropathology of a case of dopa-responsive dystonia associated with a new genetic locus, DYT14. Neurology 2002;58:1839–42. 32. Grimes DA, Han F, Lang AE, George-Hyssop St. P, Racacho L, Bulman DE. A novel locus for inherited myoclonus dystonia on 18p11. Neurology 2002;59:1183–6. 33. Grimes DA, Bulman D, George-Hyslop PS, Lang AE. Inherited myoclonus-dystonia: evidence supporting genetic heterogeneity. Mov Disord 2001;16:106–10.