Clinical characteristics.

Phosphoribosylpyrophosphate synthetase (PRS) deficiency, an X-linked disorder, is a phenotypic continuum comprising three disorders previously thought to be clinically distinct: Arts syndrome, Charcot-Marie-Tooth neuropathy X type 5 (CMTX5), and X-linked nonsyndromic sensorineural hearing loss (DFNX1). In affected males, the PRS deficiency phenotypic spectrum ranges from severe congenital profound sensorineural hearing loss, intellectual disability, delayed motor development, and progressive ophthalmologic involvement (retinal dystrophy and optic atrophy) to normal cognitive abilities and relatively later-onset, somewhat milder manifestations, such as mild sensorineural hearing loss, peripheral neuropathy, and gait ataxia.

Heterozygous females can show isolated and/or milder manifestations in the PRS deficiency spectrum. To date, 40 families with PRS deficiency have been reported.

Diagnosis/testing.

The diagnosis of PRS deficiency is established in a male proband with suggestive findings and a hemizygous pathogenic variant in PRPS1 identified by molecular genetic testing. The diagnosis of PRS deficiency is usually established in a female proband with suggestive findings and a heterozygous pathogenic variant in PRPS1 identified by molecular genetic testing.

Management.

Treatment of manifestations: There is no cure for PRS deficiency. Supportive care to improve quality of life, maximize function, and reduce complications can include multidisciplinary care by specialists in neurology, physiatry, physical therapy, occupational therapy, audiology, otolaryngology, ophthalmology and low vision services, education, and medical genetics.

Surveillance: Monitoring existing manifestations, the individual's response to supportive care, and the emergence of new manifestations involves scheduled follow up with the treating specialists.

Genetic counseling.

PRS deficiency is inherited in an X-linked manner. If the mother of the proband has a PRPS1 pathogenic variant, the chance of transmitting it in each pregnancy is 50%; if the father of the proband has a PRPS1 pathogenic variant, he will transmit it to all his daughters and none of his sons. Males who inherit the pathogenic variant will be affected. Females who inherit the pathogenic variant will be heterozygotes and will be asymptomatic or show manifestations of PRS deficiency that are typically isolated and/or milder than manifestations in hemizygous males with the same pathogenic variant. The ratio of X-chromosome inactivation adds an additional variable in predicting clinical outcome in females who inherit a PRPS1 pathogenic variant. Once the PRPS1 pathogenic variant has been identified in an affected family member, heterozygote testing for at-risk female relatives and prenatal and preimplantation genetic testing are possible.

Suggestive Findings

PRS deficiency should be suspected in a male proband with the following clinical and supportive laboratory findings and family history.

Clinical findings in males

• Bilateral sensorineural hearing loss (SNHL) that is moderate to profound; prelingual or postlingual in onset; and progressive or non-progressive. Note: Hearing loss that is moderate to profound in a neonate will be detected by newborn hearing screening; however, hearing loss that is mild will not.
  Audiogram shapes are usually residual or flat [Liu et al 2013].
  Temporal bone imaging is normal [Liu et al 2013].
  Vestibular function is normal.
• Early-onset hypotonia and delayed motor development
• Peripheral motor neuropathy (axonal with later sensory involvement)
  • Motor nerve conduction velocities (NCVs) reveal delayed distal latencies and decreased amplitudes with relatively normal velocities (median motor NCV ≥38 m/s), consistent with an axonal neuropathy [Nishikura et al 2019, Shirakawa et al 2022].
  • Needle electromyography (EMG) revealed fibrillation potentials and neurogenic motor unit action potentials [Park et al 2013], positive sharp waves [Synofzik et al 2014], and chronic denervation [Robusto et al 2015].
• Intellectual disability (ID) ranging from nonexistent (DFNX1) to moderate ID (Arts syndrome)
• Liability to infections especially in the upper respiratory tract
• Ophthalmologic findings
  • Optic neuronopathy/atrophy
    • Fundoscopic examination shows bilateral optic disc pallor.
    • Visual evoked potentials demonstrate delayed latency and decreased amplitudes of P100.
  • Retinal dystrophy [Mercati et al 2020]
    • Fundoscopic examination can show patches of retinal atrophy.
    • Electroretinogram can show abnormal cone and rod responses.

Supportive laboratory findings in males

• Serum uric acid concentration is lower than average (0.13-0.16 mmol/L), although still within the normal range (i.e., 0.12-0.35 mmol/L) [de Brouwer et al 2007].
  Note: (1) Serum uric acid concentration is not zero because the enzyme PRS-II, which has the same enzyme activity as the enzyme PRS-I, is active in tissues such as liver, resulting in purine nucleotide synthesis and uric acid production. (2) However, a low/normal serum uric acid concentration may be helpful in ruling out a diagnosis of PRS superactivity, in which serum uric acid concentration is usually high.
• Purine analysis in urine
  • Absent/low hypoxanthine concentration
  • Normal range of concentration of other purines
  • When individuals with PRS deficiency are on a low-purine diet, the uric acid-to-creatinine ratio in urine may tend to be at the lower end of normal but not zero.

Clinical findings in females. In the most severe phenotype, findings include ophthalmologic manifestations, ataxia, peripheral neuropathy, and hearing loss [Almoguera et al 2014].

Family history is consistent with X-linked inheritance (e.g., no male-to-male transmission). Note: (1) In families segregating a loss-of-function PRPS1 pathogenic variant, hemizygous males are affected and heterozygous females may be asymptomatic or have variable manifestations. (2) Absence of a known family history does not preclude the diagnosis.

Establishing the Diagnosis

Male proband. The diagnosis of PRS deficiency is established in a male proband with suggestive findings and a hemizygous pathogenic (or likely pathogenic) variant in PRPS1 identified by molecular genetic testing (see Table 1).

Female proband. The diagnosis of PRS deficiency is usually established in a female proband with suggestive findings and a heterozygous pathogenic (or likely pathogenic) variant in PRPS1 identified by molecular genetic testing (see Table 1).

Note: (1) Per ACMG/AMP 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 [Richards et al 2015]. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. (2) Identification of a hemizygous or heterozygous PRPS1 variant of uncertain significance does not establish or rule out the diagnosis.

Molecular genetic testing approaches can include a combination of gene-targeted testing (single gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing). Gene-targeted testing requires that the clinician determine which gene(s) are likely involved (see Option 1), whereas comprehensive genomic testing does not (see Option 2).

Note: Single-gene testing (sequence analysis of PRPS1, followed by gene-targeted deletion/duplication analysis) is rarely useful and typically NOT recommended.

Clinical Description

The phenotype of phosphoribosylpyrophosphate synthetase (PRS) deficiency is now known to be a continuum encompassing three previously clinically defined disorders – Arts syndrome, Charcot-Marie-Tooth neuropathy X type 5 (CMTX5), and X-linked nonsyndromic sensorineural hearing loss (DFNX1). Arts syndrome (characterized by intellectual disability, hypotonia, ataxia, sensorineural hearing impairment, and progressive optic atrophy and/or retinopathy), CMTX5 (characterized by peripheral neuropathy, sensorineural hearing loss, and optic neuropathy), and DFNX1 were initially thought to represent distinct phenotypes. However, following the observation in a single family of a male with features of CMTX5 and Arts syndrome and a female with prelingual DFNX1, Synofzik et al [2014] concluded that these disorders are not distinct entities, but rather clusters on a phenotypic continuum associated with PRS deficiency.

Subsequent reports confirmed this observation and further expanded the PRS deficiency phenotype:

• Detailed clinical and neurophysiologic examination of males diagnosed with PRPS1-related hearing loss revealed peripheral neuropathy ranging from subclinical axonal motor neuropathy to axonal sensorimotor neuropathy [Robusto et al 2015].
• Females heterozygous for a PRPS1 pathogenic missense variant were found to have optic atrophy and retinal dystrophy [Almoguera et al 2014].
• Mercati et al [2020] reported a male with profound developmental delay and multiorgan involvement.

Thus, the phenotypic spectrum of PRS deficiency can range from profound congenital sensorineural hearing impairment, intellectual disability, delayed motor development, and progressive optic atrophy [Arts et al 1993, de Brouwer et al 2007] to relatively later-onset, somewhat milder manifestations, such as mild sensorineural hearing loss, peripheral neuropathy, gait ataxia, and normal cognitive abilities.

To date, 40 families have been identified with PRS deficiency [Mercati et al 2020, Puusepp et al 2020, Rezende Filho et al 2021, Shirakawa et al 2022]. The following description of the phenotypic features associated with this condition is based on these reports.

Genotype-Phenotype Correlations

In the wide and continuous spectrum of clinical manifestations associated with PRPS1 missense variants that result in a loss of function, a relationship between the type (location) of disruption of the PRS-I enzyme and phenotype has been suggested. The most severe phenotypes are caused by variants that are predicted to affect allosteric and active sites, and the milder phenotypes are caused by variants that are predicted to disrupt the structure locally [de Brouwer et al 2010].

In females, who predictably have less severe manifestations, the ratio of X-chromosome inactivation adds an additional variable in predicting clinical outcome [Synofzik et al 2014].

Prevalence

To date, 40 families with PRS deficiency have been identified worldwide deficiency [Rosenberg & Chutorian 1967, Arts et al 1993, Glick 2006, de Brouwer et al 2007, Kim et al 2007, Liu et al 2010, Liu et al 2013, Almoguera et al 2014, Synofzik et al 2014, Kim et al 2016, Maruyama et al 2016, Mercati et al 2020, Puusepp et al 2020, Lenherr et al 2021, Rezende Filho et al 2021, Shirakawa et al 2022].

Nomenclature

Charcot-Marie-Tooth neuropathy X type 5 (CMTX5) was previously referred to as Rosenberg-Chutorian syndrome [Kim et al 2007].

DFNX1 nonsyndromic hearing loss and deafness was previously referred to as DFN2 (OMIM 304500).

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with PRS deficiency, the evaluations summarized in Table 2 (if not performed as part of the evaluation that led to diagnosis) are recommended.

Treatment of Manifestations

There is no cure for PRS deficiency.

Supportive care to improve quality of life, maximize function, and reduce complications is recommended. This can include multidisciplinary care by specialists in neurology, physiatry, physical therapy, occupational therapy, audiology, otolaryngology, ophthalmology and low vision services, education, and medical genetics (see Table 3).

Surveillance

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations listed in Table 4 are recommended.

Evaluation of Relatives at Risk

It is appropriate to clarify the genetic status of apparently asymptomatic older and younger male and female sibs of a proband in order to identify sibs at risk for hearing loss who may benefit from appropriate early support and management.

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

Therapies Under Investigation

Dietary supplementation with S-adenosylmethionine (SAM) has been investigated in individuals with PRPS1-related disorders [Authors, personal observation].

An anecdotal study suggested that co-therapy of SAM and nicotinamide riboside may be of additional clinical benefit [Lenherr et al 2021].

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.

Mode of Inheritance

Phosphoribosylpyrophosphate synthetase (PRS) deficiency is inherited in an X-linked manner.

Risk to Family Members

Parents of a male proband

• The father of an affected male will not have the disorder nor will he be hemizygous for the PRPS1 pathogenic variant; therefore, he does not require further evaluation/testing.
• In a family with more than one affected individual, the mother of an affected male is an obligate heterozygote. Note: If a woman has more than one affected child and no other affected relatives and if the PRPS1 pathogenic variant cannot be detected in her leukocyte DNA, she most likely has germline mosaicism.
• If a male is the only affected family member (i.e., a simplex case), the mother may be a heterozygote, the affected male may have a de novo PRPS1 pathogenic variant (in which case the mother is not a heterozygote), or the mother may have somatic/germline mosaicism.
  • The frequency of de novo pathogenic variants is not known.
  • Maternal germline mosaicism has not been reported to date but remains a possibility.
• Molecular genetic testing of the mother is recommended to confirm her genetic status and to allow reliable recurrence risk assessment.

Parents of a female proband

• A female proband may have inherited the PRPS1 pathogenic variant from either her mother or her father, or the pathogenic variant may be de novo.
• Detailed evaluation of the parents and review of the extended family history may help distinguish probands with a de novo pathogenic variant from those with an inherited pathogenic variant. Molecular genetic testing of the mother (and possibly the father, or subsequently the father) can determine if the pathogenic variant was inherited.

Sibs of a male proband. The risk to sibs depends on the genetic status of the mother:

• If the mother of the proband has a PRPS1 pathogenic variant, the chance of transmitting it in each pregnancy is 50%.
  • Males who inherit the pathogenic variant will be affected.
  • Females who inherit the pathogenic variant will be heterozygotes and will be asymptomatic or show manifestations of PRS deficiency that are typically isolated and/or milder than manifestations in hemizygous males with the same pathogenic variant. The ratio of X-chromosome inactivation adds an additional variable in predicting clinical outcome in females who inherit a PRPS1 pathogenic variant. See Clinical Description, Heterozygous Females.
• If the proband represents a simplex case and if the PRPS1 pathogenic variant cannot be detected in the leukocyte DNA of the mother, the risk to sibs is presumed to be low but greater than that of the general population because of the possibility of maternal germline mosaicism.

Sibs of a female proband. The risk to sibs depends on the genetic status of the parents:

• If the mother of the proband has a PRPS1 pathogenic variant, the chance of transmitting it in each pregnancy is 50%.
• If the father of the proband has a PRPS1 pathogenic variant, he will transmit it to all his daughters and none of his sons.
• If the proband represents a simplex case and if the PRPS1 pathogenic variant cannot be detected in the leukocyte DNA of the mother, the risk to sibs is presumed to be low but greater than that of the general population because of the possibility of parental germline mosaicism.

Offspring of a male proband. Males with PRS deficiency transmit the PRPS1 pathogenic variant to:

• All of their daughters, who will be heterozygotes and will be asymptomatic or show manifestations of PRS deficiency that are typically isolated and/or milder than manifestations in hemizygous males with the same pathogenic variant (see Clinical Description, Heterozygous Females);
• None of their sons.

Offspring of a female proband. Women with a PRPS1 pathogenic variant have a 50% chance of transmitting the pathogenic variant to each child.

Other family members. If a parent of the proband also has a pathogenic variant, relatives of the heterozygous/hemizygous parent may be at risk of having a PRPS1 pathogenic variant and manifestations of PRS deficiency.

Note: Molecular genetic testing may be able to identify the family member in whom a de novo pathogenic variant arose, information that could help determine genetic risk status of the extended family.

Heterozygote Detection

Identification of female heterozygotes requires either prior identification of the PRPS1 pathogenic variant in the family or, if an affected male is not available for testing, molecular genetic testing first by sequence analysis, and if no pathogenic variant is identified, by gene-targeted deletion/duplication analysis.

Note: Females who are heterozygous for this X-linked disorder may develop clinical findings related to the disorder (see Clinical Description, Heterozygous Females).

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 or at risk of having a PRPS1 pathogenic variant.

Prenatal Testing and Preimplantation Genetic Testing

Once the PRPS1 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing 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.

Molecular Pathogenesis

PRPS1 encodes the enzyme phosphoribosyl pyrophosphate synthetase I (PRS-I), which catalyzes the phosphoribosylation of ribose 5-phosphate to 5-phosphoribosyl-1-pyrophosphate, which is necessary for the de novo and salvage pathways of purine and pyrimidine biosynthesis.

Mechanism of disease causation. Missense variants that cause a loss of function of PRPS1

PRPS1-specific laboratory technical considerations. For PRPS1 missense variants of uncertain significance, PRS-I enzyme analysis can be performed. PRS deficiency is confirmed if:

• PRS-I enzyme activity is absent in erythrocytes (because PRS-I is the only isoform present);
• PRS-I enzyme activity is significantly lower in fibroblasts than in controls [de Brouwer et al 2007].

Author Notes

Contact Dr Arjan de Brouwer or Prof John Christodoulou to inquire about review of PRPS1 variants of uncertain significance.

Acknowledgments

The authors are grateful to the families of the Dutch and Australian patients for providing samples used for biochemical and molecular analyses over a number of years. The research conducted at the Murdoch Children's Research Institute (MCRI) was supported by the Victorian Government's Operational Infrastructure Support Program. The Chair in Genomic Medicine awarded to JC is generously supported by The Royal Children's Hospital Foundation.

Author History

Arjan PM de Brouwer, PhD (2008-present)
John Christodoulou, MBBS, PhD (2008-present)
John A Duley, PhD; University of Queensland (2008-2018)

Revision History

• 8 June 2023 (bp) Comprehensive update posted live
• 22 March 2018 (sw) Comprehensive update posted live
• 29 March 2011 (cd) Revision: edits to Differential Diagnosis
• 4 January 2011 (cd) Revision: changes to Therapies Under Investigation
• 18 November 2010 (me) Comprehensive update posted live
• 21 October 2008 (me) Review posted live
• 3 June 2008 (apmb) Original submission

Literature Cited

• Almoguera B, He S, Corton M, Fernandez-San Jose P, Blanco-Kelly F, López-Molina MI, García-Sandoval B, Del Val J, Guo Y, Tian L, Liu X, Guan L, Torres RJ, Puig JG, Hakonarson H, Xu X, Keating B, Ayuso C. Expanding the phenotype of PRPS1 syndromes in females: neuropathy, hearing loss and retinopathy. Orphanet J Rare Dis. 2014;9:190. [PMC free article: PMC4272780] [PubMed: 25491489]
• Arts WF, Loonen MC, Sengers RC, Slooff JL. X-linked ataxia, weakness, deafness, and loss of vision in early childhood with a fatal course. Ann Neurol. 1993;33:535–9. [PubMed: 8498830]
• Caughey AB, Krist AH, Wolff TA, Barry MJ, Henderson JT, Owens DK, Davidson KW, Simon MA, Mangione CM. USPSTF approach to addressing sex and gender when making recommendations for clinical preventive services. JAMA. 2021;326:1953–61. [PubMed: 34694343]
• de Brouwer AP, van Bokhoven H, Nabuurs SB, Arts WF, Christodoulou J, Duley J. PRPS1 mutations: four distinct syndromes and potential treatment. Am J Hum Genet. 2010;86:506–18. [PMC free article: PMC2850427] [PubMed: 20380929]
• de Brouwer AP, Williams KL, Duley JA, van Kuilenburg AB, Nabuurs SB, Egmont-Petersen M, Lugtenberg D, Zoetekouw L, Banning MJ, Roeffen M, Hamel BC, Weaving L, Ouvrier RA, Donald JA, Wevers RA, Christodoulou J, van Bokhoven H. Arts syndrome is caused by loss-of-function mutations in PRPS1. Am J Hum Genet. 2007;81:507–18. [PMC free article: PMC1950830] [PubMed: 17701896]
• Glick N. Dramatic reduction in self-injury in Lesch-Nyhan disease following S-adenosylmethionine administration. J Inherit Metab Dis. 2006;29:687. [PubMed: 16906475]
• Kim HJ, Sohn KM, Shy ME, Krajewski KM, Hwang M, Park JH, Jang SY, Won HH, Choi BO, Hong SH, Kim BJ, Suh YL, Ki CS, Lee SY, Kim SH, Kim JW. Mutations in PRPS1, which encodes the phosphoribosyl pyrophosphate synthetase enzyme critical for nucleotide biosynthesis, cause hereditary peripheral neuropathy with hearing loss and optic neuropathy (CMTX5). Am J Hum Genet. 2007;81:552–8. [PMC free article: PMC1950833] [PubMed: 17701900]
• Kim SY, Kim AR, Kim NK, Lee C, Han JH, Kim MY, Jeon EH, Park WY, Mittal R, Yan D, Liu XZ, Choi BY. Functional characterization of a novel loss-of-function mutation of PRPS1 related to early-onset progressive nonsyndromic hearing loss in Koreans (DFNX1): potential implications on future therapeutic intervention. J Gene Med. 2016;18:353–8. [PMC free article: PMC5281059] [PubMed: 27886419]
• Lenherr N, Christodoulou J, Duley J, Dobritzsch D, Fairbanks L, Datta AN, Filges I, Gürtler N, Roelofsen J, van Kuilenburg ABP, Kemper C, West EE, Szinnai G, Huemer M. Co-therapy with S-adenosylmethionine and nicotinamide riboside improves t-cell survival and function in Arts Syndrome (PRPS1 deficiency). Mol Genet Metab Rep. 2021;26:100709. [PMC free article: PMC7823043] [PubMed: 33532242]
• Liu X, Han D, Li J, Han B, Ouyang X, Cheng J, Li X, Jin Z, Wang Y, Bitner-Glindzicz M, Kong X, Xu H, Kantardzhieva A, Eavey RD, Seidman CE, Seidman JG, Du LL, Chen ZY, Dai P, Teng M, Yan D, Yuan H. Loss-of-function mutations in the PRPS1 gene cause a type of nonsyndromic X-linked sensorineural deafness, DFN2. Am J Hum Genet. 2010;86:65–71. [PMC free article: PMC2801751] [PubMed: 20021999]
• Liu XZ, Xie D, Yuan HJ, de Brouwer AP, Christodoulou J, Yan D. Hearing loss and PRPS1 mutations: wide spectrum of phenotypes and potential therapy. Int J Audiol. 2013;52:23–8. [PMC free article: PMC4511087] [PubMed: 23190330]
• Maruyama K, Ogaya S, Kurahashi N, Umemura A, Yamada K, Hashiguchi A, Takashima H, Torres RJ, Aso K. Arts syndrome with a novel missense mutation in the PRPS1 gene: a case report. Brain Dev. 2016;38:954–8. [PubMed: 27256512]
• Mercati O, Abi Warde MT, Lina-Granade G, Rio M, Heide S, de Lonlay P, Ceballos-Picot I, Robert MP, Couloigner V, Beltrand J, Boddaert N, Rodriguez D, Rubinato E, Lapierre JM, Merlette C, Sanquer S, Rötig A, Prokisch H, Lyonnet S, Loundon N, Kaplan J, Bonnefont JP, Munnich A, Besmond C, Jonard L, Marlin S. PRPS1 loss-of-function variants, from isolated hearing loss to severe congenital encephalopathy: new cases and literature review. Eur J Med Genet. 2020;63:104033. [PubMed: 32781272]
• Nishikura N, Yamagata T, Morimune T, Matsui J, Sokoda T, Sawai C, Sakaue Y, Higuchi Y, Hashiguchi A, Takashima H, Takeuchi Y, Maruo Y. X-linked Charcot-Marie-Tooth disease type 5 with recurrent weakness after febrile illness. Brain Dev. 2019;41:201–4. [PubMed: 30177296]
• Park J, Hyun YS, Kim YJ, Nam SH, Kim SH, Hong YB, Park JM, Chung KW, Choi BO. Exome sequencing reveals a novel PRPS1 mutation in a family with CMTX5 without optic atrophy. J Clin Neurol. 2013;9:283–8. [PMC free article: PMC3840141] [PubMed: 24285972]
• Puusepp S, Reinson K, Pajusalu S, van Kuilenburg ABP, Dobritzsch D, Roelofsen J, Stenzel W, Õunap K. Atypical presentation of Arts syndrome due to a novel hemizygous loss-of-function variant in the PRPS1 gene. Mol Genet Metab Rep. 2020;25:100677. [PMC free article: PMC7689168] [PubMed: 33294372]
• Rezende Filho FM, Palma MM, Pedroso JL, Barsottini OG, Sallum JM. PRPS1 gene mutation causes complex X-linked adult-onset cerebellar ataxia in women. Neurol Genet. 2021;7:e563. [PMC free article: PMC8063620] [PubMed: 33898739]
• Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405–24. [PMC free article: PMC4544753] [PubMed: 25741868]
• Robusto M, Fang M, Asselta R, Castorina P, Previtali SC, Caccia S, Benzoni E, De Cristofaro R, Yu C, Cesarani A, Liu X, Li W, Primignani P, Ambrosetti U, Xu X, Duga S, Soldà G. The expanding spectrum of PRPS1-associated phenotypes: three novel mutations segregating with X-linked hearing loss and mild peripheral neuropathy. Eur J Hum Genet. 2015;23:766–73. [PMC free article: PMC4270732] [PubMed: 25182139]
• Rosenberg RN, Chutorian A. Familial opticoacoustic nerve degeneration and polyneuropathy. Neurology. 1967;17:827–32. [PubMed: 6069085]
• Shirakawa S, Murakami T, Hashiguchi A, Takashima H, Hasegawa H, Ichida K, Sunada Y. A novel PRPS1 mutation in a Japanese patient with CMTX5. Intern Med. 2022;61:1749–51. [PMC free article: PMC9259300] [PubMed: 34803094]
• 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]
• Synofzik M, Müller vom Hagen J, Haack TB, Wilhelm C, Lindig T, Beck-Wödl S, Nabuurs SB, van Kuilenburg AB, de Brouwer AP, Schöls L. X-linked Charcot-Marie-Tooth disease, Arts syndrome, and prelingual non-syndromic deafness form a disease continuum: evidence from a family with a novel PRPS1 mutation. Orphanet J Rare Dis. 2014;9:24. [PMC free article: PMC3931488] [PubMed: 24528855]