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Spinocerebellar Ataxia with Axonal Neuropathy Type 1

Synonym: SCAN1, TDP1-Related Spinocerebellar Ataxia with Axonal Neuropathy

, MD, Dr Med Sci, FRCPCH, , MD, PhD, and , MD, PhD.

Author Information and Affiliations

Initial Posting: ; Last Update: June 30, 2022.

Estimated reading time: 14 minutes

Summary

Clinical characteristics.

Spinocerebellar ataxia with axonal neuropathy type 1 (SCAN1) is characterized by late-childhood-onset slowly progressive cerebellar ataxia and distal sensorimotor axonal neuropathy. Gaze nystagmus and dysarthria usually develop after the onset of ataxic gait. As the disease advances, pain and touch sensation in the hands and feet become impaired; vibration sense is lost in hands and lower thighs. Individuals with advanced disease develop a steppage gait and pes cavus and eventually become wheelchair dependent. Cognitive dysfunction – present in some – manifests as mild intellectual disability and poor executive function. To date only seven affected individuals have been described from three apparently unrelated consanguineous families (one from Saudi Arabia and two from Oman); therefore, it is likely that the full phenotypic spectrum of this disorder is not yet known.

Diagnosis/testing.

The diagnosis of SCAN1 is established in a proband with suggestive findings and biallelic pathogenic (or likely pathogenic) variants in TDP1 identified by molecular genetic testing.

Management.

Treatment of manifestations: Supportive care provided by specialists in neurology, rehabilitation medicine, occupational therapy, physical therapy, speech-language pathology, and clinical genetics.

Surveillance: Routine follow up as determined by treating specialists to monitor the response to supportive care and to assess for changes in existing manifestations and/or emergence of new manifestations.

Agents/circumstances to avoid: Because TDP1 codes for a DNA repair enzyme, genotoxic anti-cancer drugs such as camptothecins (e.g., irinotecan and topotecan) and bleomycin are likely to be extremely harmful and possibly fatal; exposure to radiation is also likely to be extremely harmful and possibly fatal.

Genetic counseling.

SCAN1 is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a TDP1 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of inheriting neither of the familial pathogenic variants. Once the TDP1 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal and preimplantation genetic testing are possible.

Diagnosis

No consensus clinical diagnostic criteria for spinocerebellar ataxia with axonal neuropathy type 1 (SCAN1) have been published.

Suggestive Findings

SCAN1 is suspected in individuals with the following clinical findings, electrophysiologic studies, laboratory findings, brain imaging, and family history [Takashima et al 2002, Scott et al 2019].

Clinical findings

  • Slowly progressive disorder beginning in late childhood to early adulthood (ages 13-27 years)
  • Cerebellar ataxia manifesting initially as gait ataxia and subsequently as dysarthria
  • Distal sensorimotor neuropathy manifesting initially as areflexia and subsequently as weakness and loss of sensation
  • Cognitive dysfunction in some, manifesting as mild intellectual disability and poor executive function
  • Absence of:
    • Oculomotor apraxia
    • Extraneurologic findings

Nerve conduction studies / electromyogram findings are consistent with distal axonal neuropathy.

Laboratory findings. Mildly decreased serum albumin, hypercholesterolemia, and elevated serum alpha fetoprotein support the diagnosis of SCAN1.

Brain MRI shows cerebellar atrophy especially of the vermis.

Family history is consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis.

Establishing the Diagnosis

The diagnosis of SCAN1 is established in a proband with suggestive findings and biallelic pathogenic (or likely pathogenic) variants in TDP1 identified by molecular genetic testing (see Table 1).

Note: (1) Per ACMG variant interpretation guidelines, the terms "pathogenic variants" and "likely pathogenic variants" are synonymous in a clinical setting, meaning that both are considered diagnostic and both can be used for clinical decision making. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. (2) Identification of biallelic TDP1 variants of uncertain significance (or identification of one known TDP1 pathogenic variant and one TDP1 variant of uncertain significance) does not establish or rule out a diagnosis of this disorder.

Because the phenotype of SCAN1 is indistinguishable from many other inherited disorders with ataxia, recommended molecular genetic testing approaches include use of a multigene panel or comprehensive genomic testing.

  • An ataxia multigene panel that includes TDP1 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
    For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
  • Comprehensive genomic testing does not require the clinician to determine which genes are likely involved. Exome sequencing is most commonly used; genome sequencing is also possible.
    For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.

Table 1.

Molecular Genetic Testing Used in Spinocerebellar Ataxia with Axonal Neuropathy Type 1

Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method
TDP1 Sequence analysis 3All variants reported to date 4
Gene-targeted deletion/duplication analysis 5None reported to date 4
1.
2.

See Molecular Genetics for information on variants detected in this gene.

3.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

4.

Takashima et al [2002], Scott et al [2019], and data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020]

5.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

Clinical Characteristics

Clinical Description

Spinocerebellar ataxia with axonal neuropathy type 1 (SCAN1) is characterized by progressive ataxia, cerebellar atrophy, and distal sensorimotor axonal neuropathy based on findings in three persons in a consanguineous family from Saudi Arabia [Takashima et al 2002] and four affected individuals from two apparently unrelated consanguineous families from Oman [Scott et al 2019]. The following description of the phenotypic features associated with this condition is based on these two reports.

Cerebellar ataxia. Ataxic gait appears in the second decade of life between ages 13 and 15 years. The ataxia progresses slowly, initially manifesting as mild incoordination of the upper limbs and lower limbs and then progressing to inability to walk.

Horizontal gaze-evoked nystagmus and mild dysarthria usually develop after the onset of ataxic gait.

Neuropathy. Weakness initially develops in the hands and feet with preserved strength of the more proximal upper and lower leg muscles. Progression of the weakness is accompanied by atrophy of the muscles of the fingers and feet, fasciculations, and mild weakness.

Deep tendon reflexes are lost in the third decade of life.

Sensory function is initially preserved. As the disease advances, pain, cold, and touch sensations become severely impaired in the hands and lower thigh. Vibration sense disappears in the hands and legs.

In the advanced stages of the disease, affected persons develop a steppage gait and pes cavus.

Dysphagia develops with progression of the cerebellar ataxia.

Cognitive function. Mildly impaired intellectual capacity has been observed [Scott et al 2019].

Other. One individual developed adult-onset epilepsy (grand mal) [Takashima et al 2002].

Genotype-Phenotype Correlations

No genotype-phenotype correlations are known as the data available are too limited [Takashima et al 2002, Scott et al 2019].

Nomenclature

SCAN1 may also be referred to as "TDP1-related spinocerebellar ataxia with axonal neuropathy" based on the dyadic naming approach proposed by Biesecker et al [2021] to delineate mendelian genetic disorders.

Prevalence

Spinocerebellar ataxia with axonal neuropathy type 1 (SCAN1) is very rare.

To date, one extended family from Saudi Arabia with nine affected individuals [Takashima et al 2002] and two apparently unrelated families from Oman [Scott et al 2019] have been reported with the same variant, c.1478A>G; p.His493Arg. A shared homozygous haplotype identified in the probands from the Omani families suggests a founder haplotype [Scott et al 2019]. Although haplotype studies were not performed on the Saudi Arabian family, it may share ancestral origin with the Omani individuals.

Differential Diagnosis

Table 2.

Genes of Interest in the Differential Diagnosis of Spinocerebellar Ataxia with Axonal Neuropathy Type 1

GeneDisorderMOIPhenotype
ABHD12 Polyneuropathy, hearing loss, ataxia, RP, & cataract (OMIM 612674)ARPes cavus; Achilles tendon contractures; RP; ataxic &/or spastic gait; progressive sensorimotor peripheral neuropathy
APTX Ataxia w/oculomotor apraxia type 1 (AOA1)AREarly-onset cerebellar ataxia; axonal neuropathy; oculomotor apraxia; chorea or dystonia; ↓ serum concentration of albumin & ↑ total cholesterol. AOA1 can be distinguished from SCAN1 by presence of oculomotor apraxia (80% of persons w/AOA1), but this sign is not obvious in the early stages of disease.
ATM Ataxia-telangiectasia ARTelangiectasia; ataxia; cerebellar degeneration
COA7 Spinocerebellar ataxia w/axonal neuropathy 3 (OMIM 618387)ARChildhood onset; axonal motor & sensory neuropathy; cerebellar ataxia cerebellum atrophy on MRI. Clinically similar to SCAN1.
CYP27A1 Cerebrotendinous xanthomatosis ARSymmetric distal sensory loss & weakness; cerebellar ataxia; upper motor signs; enlarged tendons
ERCC4 ERCC4-related xeroderma pigmentosumARFreckle-like lesions, xerosis, & poikiloderma on sun-exposed skin; ocular abnormalities; in 25% of affected persons, progressive neurologic abnormalities
ERCC6 ERCC6-related Cockayne syndromeARID; demyelinating neuropathy; retinopathy; congenital cataracts; joint contractures; prominent nasal bridge; sensorineural hearing loss; severe motor dysfunction
FXN Friedreich ataxia (FRDA)ARSlowly progressive ataxia; depressed tendon reflexes; dysarthria; muscle weakness; lower-limb spasticity; optic nerve atrophy; scoliosis; bladder dysfunction; loss of position & vibration senses; onset age usually <25 yrs
MRE11 Ataxia-telangiectasia-like disorder (OMIM 604391)ARSimilar to ataxia-telangiectasia; cerebellar degeneration; normal intellect
PHYH PHYH-related Refsum diseaseARChildhood to adult onset; night blindness; demyelinating neuropathy; anosmia; ataxia; RP
PNKP Ataxia w/oculomotor apraxia type 4 (OMIM 616267)ARChildhood onset; dystonia; ataxia; oculomotor apraxia; cognitive impairment
POLG POLG-related ataxia neuropathy spectrum 1 (See POLG-Related Disorders.)ARAdolescent to adult onset; sensory loss; ataxia; ophthalmoplegia
SACS ARSACS ARNeuropathy; ataxia; spasticity; ID; prominent myelinated nerve fibers
SETX Ataxia w/oculomotor apraxia type 2 (AOA2)AREarly-onset cerebellar ataxia; axonal neuropathy; oculomotor apraxia; chorea or dystonia; ↑ serum alpha-fetoprotein (AFP) level
SLC52A2 SLC52A2-related riboflavin transporter deficiencyARProgressive bulbar palsy; childhood-onset sensorineural deafness; childhood-onset neuronopathy that is more prominent as upper than lower extremity weakness; tongue fasciculations & weakness; respiratory failure; optic atrophy; ↓ visual acuity
TTPA Ataxia w/vitamin E deficiency (AVED)ARCerebellar ataxia; loss of proprioception; areflexia; markedly ↓ plasma vitamin E (alpha-tocopherol) levels. AVED can be treated by vitamin E supplementation.

Adapted from Scott et al [2019]

AR = autosomal recessive; ID = intellectual disability; MOI = mode of inheritance; RP = retinitis pigmentosa; SCAN1 = spinocerebellar ataxia with axonal neuropathy type 1

1.

The ataxia neuropathy spectrum (ANS) includes the phenotypes previously referred to as mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO).

Management

No clinical practice guidelines for spinocerebellar ataxia with axonal neuropathy type 1 (SCAN1) have been published.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with SCAN1, the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended:

  • Complete neurologic examination including use of the Scale for the Assessment and Rating of Ataxia (SARA) and assessment of muscle strength, reflexes, and sensation
  • Assessment by specialists in rehabilitation medicine, occupational therapy, and physical therapy regarding gross motor skills, fine motor skills, and need for adaptive equipment such as prostheses, walking aids, and/or wheelchairs
  • Assessment by a speech-language pathologist for evidence of dysarthria and need for ongoing speech-language therapy
  • Consultation with a medical geneticist, certified genetic counselor, or certified advanced genetic nurse to inform affected individuals and their families about the nature, mode of inheritance, and implications of SCAN1 in order to facilitate medical and personal decision making

To support the family of an individual diagnosed with SCAN1, review of the following options is recommended:

  • Use of community or online resources (e.g., Parent to Parent)
  • Social work involvement for parental support
  • Home nursing referral (if needed)
  • Ethics consultation (clinical ethics services) to assess health care decisions in the context of the best interest of the child and the values and preferences of the family

Treatment of Manifestations

There is no cure for SCAN1.

Supportive care is provided by specialists in neurology, rehabilitation medicine, occupational therapy, physical therapy, speech-language pathology, and clinical genetics.

Physical therapy may be helpful in maintaining a more active lifestyle.

Surveillance

Routine follow up as determined by treating specialists is recommended to monitor the response to supportive care and to assess for changes in existing manifestations and/or emergence of new manifestations.

Agents/Circumstances to Avoid

Likely to be extremely harmful and possibly fatal:

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members; it is not meant to address all personal, cultural, or ethical issues that may arise or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Spinocerebellar ataxia with axonal neuropathy type 1 (SCAN1) is inherited in an autosomal recessive manner.

Risk to Family Members

Parents of a proband

  • The parents of an affected child are presumed to be heterozygous for a TDP1 pathogenic variant.
  • Molecular genetic testing is recommended for the parents of a proband to confirm that both parents are heterozygous for a TDP1 pathogenic variant and to allow reliable recurrence risk assessment.
  • If a pathogenic variant is detected in only one parent and parental identity testing has confirmed biological maternity and paternity, it is possible that one of the pathogenic variants identified in the proband occurred as a de novo event in the proband or as a postzygotic de novo event in a mosaic parent [Jónsson et al 2017]. If the proband appears to have homozygous pathogenic variants (i.e., the same two pathogenic variants), additional possibilities to consider include:
  • Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.

Sibs of a proband

  • If both parents are known to be heterozygous for a TDP1 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of inheriting neither of the familial pathogenic variants.
  • Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.

Offspring of a proband

Other family members of a proband. Each sib of the proband's parents is at a 50% risk of being a carrier of a TDP1 pathogenic variant.

Carrier Detection

Carrier testing for at-risk relatives requires prior identification of the TDP1 pathogenic variants in the family.

Related Genetic Counseling Issues

Family planning

  • The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or at risk of being carriers.
  • Carrier testing for reproductive partners of known carriers should be considered, particularly if consanguinity is likely.

Prenatal Testing and Preimplantation Genetic Testing

Once the TDP1 pathogenic variants have been identified in an affected family member, prenatal testing and preimplantation genetic testing for a pregnancy at increased risk are possible.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • Ataxia UK
    United Kingdom
    Phone: 0800 995 6037; +44 (0) 20 7582 1444 (from abroad)
    Email: help@ataxia.org.uk
  • euro-ATAXIA (European Federation of Hereditary Ataxias)
    United Kingdom
    Email: lporter@ataxia.org.uk
  • Hereditary Neuropathy Foundation
    Phone: 855-435-7268 (toll-free); 212-722-8396
    Fax: 917-591-2758
    Email: info@hnf-cure.org
  • National Ataxia Foundation
    Phone: 763-553-0020
    Fax: 763-553-0167
    Email: naf@ataxia.org
  • CoRDS Registry
    Sanford Research
    Phone: 605-312-6300

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

Spinocerebellar Ataxia with Axonal Neuropathy, Autosomal Recessive: Genes and Databases

GeneChromosome LocusProteinLocus-Specific DatabasesHGMDClinVar
TDP1 14q32​.11 Tyrosyl-DNA phosphodiesterase 1 TDP1 database TDP1 TDP1

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for Spinocerebellar Ataxia with Axonal Neuropathy, Autosomal Recessive (View All in OMIM)

607198TYROSYL-DNA PHOSPHODIESTERASE 1; TDP1
607250SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE, WITH AXONAL NEUROPATHY 1; SCAN1

Molecular Pathogenesis

TDP1 encodes the nuclear protein tyrosyl-DNA phosphodiesterase 1 (TDP1), an enzyme that is a member of phospholipase D superfamily and participates in DNA damage repair by unblocking complexes of trapped topoisomerase 1 and DNA through cleavage of a diester bond. Phosphorylated TDP1 interacts with DNA ligase III alpha, a component of the single strand break repair machinery [El-Khamisy et al 2005, Das et al 2009, Chiang et al 2010].

TDP1 contains two HKD motifs that comprise the active site of this enzyme and catalyze phosphoryl transfer reactions [Interthal et al 2001].

Protein modeling showed that the pathogenic variant p.His493Arg disrupts the symmetric structure of the active center of the enzyme [Takashima et al 2002]. The mutated TDP1 protein, which has decreased enzyme activity [El-Khamisy et al 2005, Interthal et al 2005b, Zhou et al 2005, El-Khamisy & Caldecott 2007], is also less efficient at repairing topo1-DNA complexes [Interthal et al 2005b, Miao et al 2006].

In the absence of wild type TDP1 for DNA repair, the p.His493Arg TDP1 variant becomes covalently trapped in the normally transient TDP1-DNA intermediate state causing a DNA break [Interthal et al 2005a, Hirano et al 2007]. TDP1 also participates in maintenance of the mitochondrial genome and mitochondrial function. Mitochondrial dysfunction likely contributes to the pathophysiology of SCAN1 [Fam et al 2018, Huang & Pommier 2019]. Identification of additional disease-causing variants could improve understanding of the mechanism for disease causation.

Mechanism of disease causation. Functional studies suggest a recessive neomorphic (gain-of-function) mechanism for the c.1478A>G; p.His493Arg variant.

Table 3.

Notable TDP1 Pathogenic Variants

Reference SequencesDNA Nucleotide
Change
Predicted
Protein Change
Comment [Reference]
NM_018319​.4
NP_060789​.2
c.1478A>Gp.His493ArgFounder variant reported in 2 apparently unrelated Omani families [Scott et al 2019]; also reported in an unrelated Saudi Arabian family [Takashima et al 2002].

Variants listed in the table have been provided by the authors. GeneReviews staff have not independently verified the classification of variants.

GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen​.hgvs.org). See Quick Reference for an explanation of nomenclature.

Chapter Notes

Author History

Cornelius Boerkoel, MD, PhD (2007-present)
Hok Khim Fam, BSc; University of British Columbia (2012-2022)
Ryuki Hirano, MD, PhD; Kagoshima University (2007-2012)
Mustafa AM Salih, MD, Dr Med Sci, FRCPCH (2007-present)
Hiroshi Takashima, MD, PhD (2007-present)

Revision History

  • 30 June 2022 (bp) Comprehensive update posted live
  • 20 December 2012 (cd) Revision: TDP1 sequence analysis available clinically
  • 26 April 2012 (me) Comprehensive update posted live
  • 22 October 2007 (me) Review posted live
  • 26 September 2007 (cfb) Original submission

References

Literature Cited

  • Biesecker LG, Adam MP, Alkuraya FS, Amemiya AR, Bamshad MJ, Beck AE, Bennett JT, Bird LM, Carey JC, Chung B, Clark RD, Cox TC, Curry C, Dinulos MBP, Dobyns WB, Giampietro PF, Girisha KM, Glass IA, Graham JM Jr, Gripp KW, Haldeman-Englert CR, Hall BD, Innes AM, Kalish JM, Keppler-Noreuil KM, Kosaki K, Kozel BA, Mirzaa GM, Mulvihill JJ, Nowaczyk MJM, Pagon RA, Retterer K, Rope AF, Sanchez-Lara PA, Seaver LH, Shieh JT, Slavotinek AM, Sobering AK, Stevens CA, Stevenson DA, Tan TY, Tan WH, Tsai AC, Weaver DD, Williams MS, Zackai E, Zarate YA. A dyadic approach to the delineation of diagnostic entities in clinical genomics. Am J Hum Genet. 2021;108:8–15. [PMC free article: PMC7820621] [PubMed: 33417889]
  • Chiang SC, Carroll J, El-Khamisy SF. TDP1 serine 81 promotes interaction with DNA ligase IIIalpha and facilitates cell survival following DNA damage. Cell Cycle. 2010;9:588–95. [PubMed: 20009512]
  • Das BB, Antony S, Gupta S, Dexheimer TS, Redon CE, Garfield S, Shiloh Y, Pommier Y. Optimal function of the DNA repair enzyme TDP1 requires its phosphorylation by ATM and/or DNA-PK. EMBO J. 2009;28:3667–80. [PMC free article: PMC2790489] [PubMed: 19851285]
  • El-Khamisy SF, Caldecott KW. DNA single-strand break repair and spinocerebellar ataxia with axonal neuropathy-1. Neuroscience. 2007;145:1260–6. [PubMed: 17045754]
  • El-Khamisy SF, Hartsuiker E, Caldecott KW. TDP1 facilitates repair of ionizing radiation-induced DNA single-strand breaks. DNA Repair (Amst). 2007;6:1485–95. [PubMed: 17600775]
  • El-Khamisy SF, Saifi GM, Weinfeld M, Johansson F, Helleday T, Lupski JR, Caldecott KW. Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1. Nature. 2005;434:108–13. [PubMed: 15744309]
  • Fam HK, Choi K, Fougner L, Lim CJ, Boerkoel CF. Reactive oxygen species stress increases accumulation of tyrosyl-DNA phsosphodiesterase 1 within mitochondria. Sci Rep. 2018;8:4304. [PMC free article: PMC5844879] [PubMed: 29523818]
  • Hirano R, Interthal H, Huang C, Nakamura T, Deguchi K, Choi K, Bhattacharjee MB, Arimura K, Umehara F, Izumo S, Northrop JL, Salih MA, Inoue K, Armstrong DL, Champoux JJ, Takashima H, Boerkoel CF. Spinocerebellar ataxia with axonal neuropathy: consequence of a Tdp1 recessive neomorphic mutation? EMBO J. 2007;26:4732–43. [PMC free article: PMC2080798] [PubMed: 17948061]
  • Huang SN, Pommier Y. Mammalian tyrosyl-DNA phosphodiesterases in the context of mitochondrial DNA repair. Int J Mol Sci. 2019;20:3015. [PMC free article: PMC6628236] [PubMed: 31226795]
  • Interthal H, Chen HJ, Champoux JJ. Human Tdp1 cleaves a broad spectrum of substrates, including phosphoamide linkages. J Biol Chem. 2005a;280:36518–28. [PMC free article: PMC1351008] [PubMed: 16141202]
  • Interthal H, Chen HJ, Kehl-Fie TE, Zotzmann J, Leppard JB, Champoux JJ. SCAN1 mutant Tdp1 accumulates the enzyme--DNA intermediate and causes camptothecin hypersensitivity. EMBO J. 2005b;24:2224–33. [PMC free article: PMC1150888] [PubMed: 15920477]
  • Interthal H, Pouliot JJ, Champoux JJ. The tyrosyl-DNA phosphodiesterase Tdp1 is a member of the phospholipase D superfamily. Proc Natl Acad Sci U S A. 2001;98:12009–14. [PMC free article: PMC59758] [PubMed: 11572945]
  • Jónsson H, Sulem P, Kehr B, Kristmundsdottir S, Zink F, Hjartarson E, Hardarson MT, Hjorleifsson KE, Eggertsson HP, Gudjonsson SA, Ward LD, Arnadottir GA, Helgason EA, Helgason H, Gylfason A, Jonasdottir A, Jonasdottir A, Rafnar T, Frigge M, Stacey SN, Th Magnusson O, Thorsteinsdottir U, Masson G, Kong A, Halldorsson BV, Helgason A, Gudbjartsson DF, Stefansson K. Parental influence on human germline de novo mutations in 1,548 trios from Iceland. Nature. 2017;549:519–22. [PubMed: 28959963]
  • Miao ZH, Agama K, Sordet O, Povirk L, Kohn KW, Pommier Y. Hereditary ataxia SCAN1 cells are defective for the repair of transcription-dependent topoisomerase I cleavage complexes. DNA Repair (Amst). 2006;5:1489–94. [PubMed: 16935573]
  • Scott P, Al Kindi A, Al Fahdi A, Al Yarubi N, Bruwer Z, Al Adawi S, Nandhagopal R. Spinocerebellar ataxia with axonal neuropathy type 1 revisited. J Clin Neurosci. 2019;67:139–44. [PubMed: 31182267]
  • Stenson PD, Mort M, Ball EV, Chapman M, Evans K, Azevedo L, Hayden M, Heywood S, Millar DS, Phillips AD, Cooper DN. The Human Gene Mutation Database (HGMD®): optimizing its use in a clinical diagnostic or research setting. Hum Genet. 2020;139:1197–207. [PMC free article: PMC7497289] [PubMed: 32596782]
  • Takashima H, Boerkoel CF, John J, Saifi GM, Salih MA, Armstrong D, Mao Y, Quiocho FA, Roa BB, Nakagawa M, Stockton DW, Lupski JR. Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy. Nat Genet. 2002;32:267–72. [PubMed: 12244316]
  • Zhou T, Lee JW, Tatavarthi H, Lupski JR, Valerie K, Povirk LF. Deficiency in 3'-phosphoglycolate processing in human cells with a hereditary mutation in tyrosyl-DNA phosphodiesterase (TDP1). Nucleic Acids Res. 2005;33:289–97. [PMC free article: PMC546157] [PubMed: 15647511]
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