Research & Literature

RNF216 mutations as a novel cause of autosomal recessive Huntington-like disorder.

Santens P, Van Damme T, Steyaert W, et al.

Neurology 2015; (84(17)):1760-6 doi:10.1212/WNL.0000000000001521.

Decreasing fall risk in spinocerebellar ataxia.

Santos de Oliveira LA, Martins CP, Horsczaruk CH, et al.

Journal of physical therapy science 2015; (27(4)):1223-5 doi:10.1589/jpts.27.1223.

Psychiatric disorders, spinocerebellar ataxia type 3 and CAG expansion.

Silva UC, Marques W, Lourenço CM, et al.

Journal of neurology 2015; (262(7)):1777-9 doi:10.1007/s00415-015-7807-3.

Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism--pathogenesis, diagnosis and treatment.

Boehm U, Bouloux PM, Dattani MT, et al.

Nature reviews. Endocrinology 2015; (11(9)):547-64 doi:10.1038/nrendo.2015.112.

Bone involvement in males with Kallmann disease.

Iolascon G, Frizzi L, Bianco M, et al.

Aging clinical and experimental research 2015; (27 Suppl 1()):S31-6 doi:10.1007/s40520-015-0421-5.

Recessive Mutations in POLR3B Encoding RNA Polymerase III Subunit Causing Diffuse Hypomyelination in Patients with 4H Leukodystrophy with Polymicrogyria and Cataracts.

Jurkiewicz E, Dunin-Wąsowicz D, Gieruszczak-Białek D, et al.

Clinical neuroradiology 2017; (27(2)):213-220 doi:10.1007/s00062-015-0472-1.

Guidelines for treatment of immune-mediated cerebellar ataxias.

Mitoma H, Hadjivassiliou M, Honnorat J

Cerebellum & ataxias 2015; (2()):14 doi:10.1186/s40673-015-0034-y.

Ataxia and Hypogonadotropic Hypogonadism with Intrafamilial Variability Caused by RNF216 Mutation.

Alqwaifly M, Bohlega S

Neurology international 2016; (8(2)):6444 doi:10.4081/ni.2016.6444.

Ataxia.

Ashizawa T, Xia G

Continuum (Minneapolis, Minn.) 2016; (22(4 Movement Disorders)):1208-26 doi:10.1212/CON.0000000000000362.

Endocrine Society of Australia position statement on male hypogonadism (part 1): assessment and indications for testosterone therapy.

Yeap BB, Grossmann M, McLachlan RI, et al.

The Medical journal of Australia 2016; (205(4)):173-8 doi:10.5694/mja16.00393.

Boucher Neuhäuser Syndrome - A rare cause of inherited hypogonadotropic hypogonadism. A case of two adult siblings with two novel mutations in PNPLA6.

Langdahl JH, Frederiksen AL, Nguyen N, et al.

European journal of medical genetics 2017; (60(2)):105-109 doi:10.1016/j.ejmg.2016.11.003.

GAD65 neurological autoimmunity.

McKeon A, Tracy JA

Muscle & nerve 2017; (56(1)):15-27 doi:10.1002/mus.25565.

STUB1/CHIP mutations cause Gordon Holmes syndrome as part of a widespread multisystemic neurodegeneration: evidence from four novel mutations.

Hayer SN, Deconinck T, Bender B, et al.

Orphanet journal of rare diseases 2017; (12(1)):31 doi:10.1186/s13023-017-0580-x.

Complicated acute cerebellitis with obstructive hydrocephalus and tonsillar herniation in a child.

Venkatesh M, Chakkalakkoombil SV, Duraipandi MB, Gulati R

BMJ case reports 2017; (2017()) doi:10.1136/bcr-2017-219337.

Hypomorphic mutations in POLR3A are a frequent cause of sporadic and recessive spastic ataxia.

Minnerop M, Kurzwelly D, Wagner H, et al.

Brain : a journal of neurology 2017; (140(6)):1561-1578 doi:10.1093/brain/awx095.

Cerebellar disease associated with anti-glutamic acid decarboxylase antibodies: review.

Baizabal-Carvallo JF, Alonso-Juarez M

Journal of neural transmission (Vienna, Austria : 1996) 2017; (124(10)):1171-1182 doi:10.1007/s00702-017-1754-3.

4H Leukodystrophy: Lessons from 3T Imaging.

Cayami FK, Bugiani M, Pouwels PJW, et al.

Neuropediatrics 2018; (49(2)):112-117 doi:10.1055/s-0037-1608780.

[Cerebellar Ataxia and Autoantibodies].

Nanri K, Yoshikura N, Kimura A, et al.

Brain and nerve = Shinkei kenkyu no shinpo 2018; (70(4)):371-382 doi:10.11477/mf.1416201010.

Transition in Pediatric and Adolescent Hypogonadal Girls: Gynecological Aspects, Estrogen Replacement Therapy, and Contraception.

Tønnes Pedersen A, Cleemann L, Main KM, Juul A

Endocrine development 2018; (33()):113-127 doi:10.1159/000487529.

Gordon Holmes syndrome due to compound heterozygosity of two new PNPLA6 variants - A diagnostic challenge.

Salgado P, Carvalho R, Brandão AF, et al.

eNeurologicalSci 2019; (14()):9-12 doi:10.1016/j.ensci.2018.11.022.

Clinical Management of Congenital Hypogonadotropic Hypogonadism.

Young J, Xu C, Papadakis GE, et al.

Endocrine reviews 2019; (40(2)):669-710 doi:10.1210/er.2018-00116.

RNF216 Regulates the Migration of Immortalized GnRH Neurons by Suppressing Beclin1-Mediated Autophagy.

Li F, Li D, Liu H, et al.

Frontiers in endocrinology 2019; (10()):12 doi:10.3389/fendo.2019.00012.

Guidelines on the diagnosis and management of the progressive ataxias.

de Silva R, Greenfield J, Cook A, et al.

Orphanet journal of rare diseases 2019; (14(1)):51 doi:10.1186/s13023-019-1013-9.

Testosterone replacement in congenital hypogonadotropic hypogonadism maintains bone density but has only limited osteoanabolic effects.

Antonio L, Caerels S, Jardi F, et al.

Andrology 2019; (7(3)):302-306 doi:10.1111/andr.12604.

Degenerative and acquired sporadic adult onset ataxia.

Lieto M, Roca A, Santorelli FM, et al.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 2019; (40(7)):1335-1342 doi:10.1007/s10072-019-03856-w.

Ataxia.

Kuo SH

Continuum (Minneapolis, Minn.) 2019; (25(4)):1036-1054 doi:10.1212/CON.0000000000000753.

Epilepsy in spinocerebellar ataxia type 8: a case report.

Swaminathan A

Journal of medical case reports 2019; (13(1)):333 doi:10.1186/s13256-019-2270-x.

European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males: Endorsing organization: European Society of Endocrinology.

Corona G, Goulis DG, Huhtaniemi I, et al.

Andrology 2020; (8(5)):970-987 doi:10.1111/andr.12770.

Clinical and Genetic Characterization of Autosomal Recessive Spinocerebellar Ataxia Type 16 (SCAR16) in Taiwan.

Chiu HH, Hsaio CT, Tsai YS, et al.

Cerebellum (London, England) 2020; (19(4)):544-549 doi:10.1007/s12311-020-01136-4.

Features of speech and swallowing dysfunction in pre-ataxic spinocerebellar ataxia type 2.

Vogel AP, Magee M, Torres-Vega R, et al.

Neurology 2020; (95(2)):e194-e205 doi:10.1212/WNL.0000000000009776.

Delayed puberty.

Butler G, Purushothaman P

Minerva pediatrica 2020; (72(6)):484-490 doi:10.23736/S0026-4946.20.05968-X.

Expanding the clinical spectrum of STIP1 homology and U-box containing protein 1-associated ataxia.

Ravel JM, Benkirane M, Calmels N, et al.

Journal of neurology 2021; (268(5)):1927-1937 doi:10.1007/s00415-020-10348-x.

The cerebellar cognitive affective syndrome scale reveals early neuropsychological deficits in SCA3 patients.

Maas RPPWM, Killaars S, van de Warrenburg BPC, Schutter DJLG

Journal of neurology 2021; (268(9)):3456-3466 doi:10.1007/s00415-021-10516-7.

A de novo STUB1 variant associated with an early adult-onset multisystemic ataxia phenotype.

Mengel D, Traschütz A, Reich S, et al.

Journal of neurology 2021; (268(10)):3845-3851 doi:10.1007/s00415-021-10524-7.

Respiratory dysfunction in a mouse model of spinocerebellar ataxia type 7.

Fusco AF, Pucci LA, Switonski PM, et al.

Disease models & mechanisms 2021; (14(7)) doi:10.1242/dmm.048893.

Diagnosis of Male Central Hypogonadism During Childhood.

Grinspon RP, Castro S, Brunello FG, et al.

Journal of the Endocrine Society 2021; (5(11)):bvab145 doi:10.1210/jendso/bvab145.

Multifaceted and Age-Dependent Phenotypes Associated With Biallelic PNPLA6 Gene Variants: Eight Novel Cases and Review of the Literature.

Nanetti L, Di Bella D, Magri S, et al.

Frontiers in neurology 2021; (12()):793547 doi:10.3389/fneur.2021.793547.

Functional Outcomes Associated With Independence in Walking Among People With Hereditary Ataxias: An Exploratory Cross-sectional Study.

Giangiardi VF, Perracini MR, da Silva ML, et al.

Physical therapy 2022; (102(4)) doi:10.1093/ptj/pzac006.

The inherited cerebellar ataxias: an update.

Coarelli G, Wirth T, Tranchant C, et al.

Journal of neurology 2023; (270(1)):208-222 doi:10.1007/s00415-022-11383-6.

Neurodegenerative Cerebellar Ataxia.

Rosenthal LS

Continuum (Minneapolis, Minn.) 2022; (28(5)):1409-1434 doi:10.1212/CON.0000000000001180.

Ataxias: Hereditary, Acquired, and Reversible Etiologies.

Lin CR, Kuo SH

Seminars in neurology 2023; (43(1)):48-64 doi:10.1055/s-0043-1763511.

Ataxia and Hypogonadism: a Review of the Associated Genes and Syndromes.

De Michele G, Maione L, Cocozza S, et al.

Cerebellum (London, England) 2024; (23(2)):688-701 doi:10.1007/s12311-023-01549-x.

A novel mutation in RNF216 gene in a Turkish case with Gordon Holmes syndrome.

Durmaz Çelik N, Erzurumluoğlu E, Özben S, et al.

BMC medical genomics 2023; (16(1)):98 doi:10.1186/s12920-023-01529-4.

Pulsatile gonadotropin-releasing hormone: clinical applications of a physiologic paradigm.

Filicori M

F&S reports 2023; (4(2 Suppl)):20-26 doi:10.1016/j.xfre.2023.01.007.

PNPLA6 disorders: what's in a name?

Liu J, Hufnagel RB

Ophthalmic genetics 2023; (44(6)):530-538 doi:10.1080/13816810.2023.2254830.

Inborn Errors of Metabolism with Ataxia: Current and Future Treatment Options.

Bremova-Ertl T, Hofmann J, Stucki J, et al.

Cells 2023; (12(18)) doi:10.3390/cells12182314.

Clinical and genetic spectrum of RNF216-related disorder: a new case and literature review.

Wu C, Zhang Z

Journal of medical genetics 2024; (61(5)):430-434 doi:10.1136/jmg-2023-109397.

Gonadotropins for pubertal induction in males with hypogonadotropic hypogonadism: systematic review and meta-analysis.

Alexander EC, Faruqi D, Farquhar R, et al.

European journal of endocrinology 2024; (190(1)):S1-S11 doi:10.1093/ejendo/lvad166.

Hypogonadotropic Hypogonadism.

Bangalore Krishna K, Fuqua JS, Witchel SF

Endocrinology and metabolism clinics of North America 2024; (53(2)):279-292 doi:10.1016/j.ecl.2024.01.008.

Hypogonadotropic Hypogonadism as First Presentation of the Severe Neuroendocrine Disorder Caused by RNF216.

Rochtus A, Asscherickx W, Timmers M, et al.

JCEM case reports 2024; (2(11)):luae195 doi:10.1210/jcemcr/luae195.

Efficacy of Gonadotropin Treatment for Induction of Spermatogenesis in Men With Pathologic Gonadotropin Deficiency: A Meta-Analysis.

Muir CA, Zhang T, Jayadev V, et al.

Clinical endocrinology 2025; (102(2)):167-177 doi:10.1111/cen.15151.

Goal-Directed Rehabilitation Versus Standard Care for Individuals with Hereditary Cerebellar Ataxia: A Multicenter, Single-Blind, Randomized Controlled Superiority Trial.

Milne SC, Roberts M, Williams S, et al.

Annals of neurology 2025; (97(3)):409-424 doi:10.1002/ana.27130.

Movement Disorders in Hereditary Cerebellar Ataxia.

Damásio J, Costa S, Moura J, et al.

Movement disorders clinical practice 2025; (12(6)):784-795 doi:10.1002/mdc3.14358.

Identification of a large homozygous RNF216 deletion in a Chinese patient with gordon holmes syndrome.

Wu B, Duan R, Pi Z, et al.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 2025; (46(8)):4001-4006 doi:10.1007/s10072-025-08169-9.

Etiologies and clinical characteristics of primary amenorrhea: A study from a quaternary care hospital in southern Thailand.

Peeyananjarassri K, Klangsin S, Bhumsiriwilai P, et al.

The journal of obstetrics and gynaecology research 2025; (51(7)):e70009 doi:10.1111/jog.70009.

Practice Recommendations for Genetic Testing of Ataxias.

Srinivasan SR, Mook AD, Rochman M, et al.

Annals of clinical and translational neurology 2025; (12(12)):2398-2409 doi:10.1002/acn3.70171.

Home Training for Cerebellar Ataxias: A Randomized Clinical Trial.

Barbuto S, Lee S, Stein J, et al.

JAMA neurology 2025; (82(11)):1162-1170 doi:10.1001/jamaneurol.2025.3421.

Article Title: Impact of Dysphagia on Quality of Life in Machado-Joseph Disease.

Mota JP, Rodrigues IT, Ferreira AF, et al.

Cerebellum (London, England) 2025; (24(6)):158 doi:10.1007/s12311-025-01911-1.

Incomplete Evidence of Bone Density Normalization Following Long-Term Reproductive Hormone Treatment in Men With Hypogonadotropic Hypogonadism.

de Silva NL, Hyams E, Grant B, et al.

The Journal of clinical endocrinology and metabolism 2025; (111(1)):280-290 doi:10.1210/clinem/dgaf488.

Novel PNPLA6 Variants: Hypogonadotropic Hypogonadism, Pituitary Hypoplasia, Anosmia, and Cerebellar Atrophy in Siblings.

Hussain MA, Kumar V, Chapla A, et al.

JCEM case reports 2026; (4(1)):luaf286 doi:10.1210/jcemcr/luaf286.

Changes in Gait After Training for Individuals With Cerebellar Ataxia.

Smani A, Lee S, Spinner M, Barbuto S

Archives of rehabilitation research and clinical translation 2025; (7(4)):100540 doi:10.1016/j.arrct.2025.100540.

Management of infertility in women with hypothalamic hypogonadotropic hypogonadism: an expert opinion.

Robin G, Maitrot-Mantelet L, Dubourdieu S, et al.

Reproductive biology and endocrinology : RB&E 2026; (24(1)).

Gonadal recovery in men with prolactinomas on cabergoline: 6-month testosterone levels as a predictor of testosterone replacement timing.

Fedai NK, Uzun N, Bostan H, et al.

Hormones (Athens, Greece) 2026; doi:10.1007/s42000-026-00766-3.

Boosting Male Fertility: The Impact of Gonadotropin Therapy on Hypogonadotropic Hypogonadism-A Systematic Review and Meta-Analysis.

Huijben M, Prinsen A, de Kort L, van Breda J

Andrology 2026; (14(7)):1971-1987 doi:10.1111/andr.70226.

Clinical and Genetic Profile of Gordon-Holmes Syndrome: A Review of Published Cases : Original Article.

Mahale RR, Mailankody P

Cerebellum (London, England) 2026; (25(3)).

Homozygous PNPLA6 Mutation (p.Arg1183Trp) Associated With Isolated Cerebellar Ataxia: A Familial Case Report.

Alawadhi A, Almarzooqi A, Khan M, Alrukn S

Cureus 2026; (18(4)):e107039 doi:10.7759/cureus.107039.

Adult Male Hypogonadism: A Review.

Anawalt BD, O'Connor KM, Grossmann M

JAMA 2026; (335(24)):2146-2159 doi:10.1001/jama.2026.8526.

Current perspectives on the pharmacologic treatment of boys and adolescents with congenital hypogonadotropic hypogonadism.

Rey RA, Grinspon RP

Expert opinion on pharmacotherapy 2026; 1-13 doi:10.1080/14656566.2026.2741490.

Substrate Profiling of RNF216 Uncovers a Translation-Linked OTUD4 Regulatory Axis.

Wei W, Liu R, Zhang J, et al.

bioRxiv : the preprint server for biology 2026; doi:10.64898/2026.08.26.747332.