Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

A female carrier of spinal and bulbar muscular atrophy diagnosed with DNAJB6-related distal myopathy


Mutations in the DNAJB6 gene cause limb girdle muscular dystrophy D1 (LGMD D1) and distal myopathy with rimmed vacuoles. With the discovery of new mutations, the phenotypic spectrum of DNAJB6-related myopathy has been extended, making the diagnosis more complicated. In this study, we describe a female carrier of spinal and bulbar muscular atrophy (SBMA) diagnosed with DNAJB6-related distal myopathy. The c.292_294delGAT (p. Asp98del) mutation in the DNAJB6 gene and a 49 CAG repeat expansion in the androgen receptor (AR) gene were identified. According to the clinical manifestations of distal-dominant lower limb involvement, a myogenic pattern in the electrophysiological study, and rimmed vacuoles on muscle pathology, the patient was ultimately diagnosed with DNAJB6-related distal myopathy. A functional study in a zebrafish model indicated that the c.292_294delGAT (p. Asp98del) mutation contributed to muscle structure defects. This study offers useful insights for the differential diagnosis of a condition in which patients carry pathogenic variants in different genes.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1
Fig. 2


  1. Sarparanta J, Jonson PH, Kawan S, Udd B. Neuromuscular diseases due to chaperone mutations: a review and some new results. Int J Mol Sci. 2020;21:1409.

  2. Sandell S, Huovinen S, Palmio J, Raheem O, Lindfors M, Zhao F, et al. Diagnostically important muscle pathology in DNAJB6 mutated LGMD1D. Acta Neuropathol Commun. 2016;4:9.

    Article  Google Scholar 

  3. Harms MB, Sommerville RB, Allred P, Bell S, Ma D, Cooper P, et al. Exome sequencing reveals DNAJB6 mutations in dominantly-inherited myopathy. Ann Neurol. 2012;71:407–16.

    Article  CAS  Google Scholar 

  4. Qian FY, Guo YD, Zu J, Zhang JH, Zheng YM, Abdoulaye IA, et al. A novel recessive mutation affecting DNAJB6a causes myofibrillar myopathy. Acta Neuropathol Commun. 2021;9:23.

    Article  CAS  Google Scholar 

  5. Ruggieri A, Saredi S, Zanotti S, Pasanisi MB, Maggi L, Mora M. DNAJB6 myopathies: focused review on an emerging and expanding group of myopathies. Front Mol Biosci. 2016;3:63.

    Article  Google Scholar 

  6. Jonson PH, Palmio J, Johari M, Penttila S, Evila A, Nelson I, et al. Novel mutations in DNAJB6 cause LGMD1D and distal myopathy in French families. Eur J Neurol. 2018;25:790–4.

    Article  CAS  Google Scholar 

  7. Ishihara H, Kanda F, Nishio H, Sumino K, Chihara K. Clinical features and skewed X-chromosome inactivation in female carriers of X-linked recessive spinal and bulbar muscular atrophy. J Neurol. 2001;248:856–60.

    Article  CAS  Google Scholar 

  8. Paradas C, Solano F, Carrillo F, Fernandez C, Bautista J, Pintado E, et al. Highly skewed inactivation of the wild-type X-chromosome in asymptomatic female carriers of spinal and bulbar muscular atrophy (Kennedy’s disease). J Neurol. 2008;255:853–7.

    Article  CAS  Google Scholar 

  9. Pellerin D, Aykanat A, Ellezam B, Troiano EC, Karamchandani J, Dicaire MJ, et al. Novel recessive TNNT1 congenital core-rod myopathy in French Canadians. Ann Neurol. 2020;87:568–83.

    Article  CAS  Google Scholar 

  10. Couthouis J, Raphael AR, Siskind C, Findlay AR, Buenrostro JD, Greenleaf WJ, et al. Exome sequencing identifies a DNAJB6 mutation in a family with dominantly-inherited limb-girdle muscular dystrophy. Neuromuscul Disord. 2014;24:431–5.

    Article  Google Scholar 

  11. Liu X, Zhu M, Li X, Tang J. Clinical manifestations and AR gene mutations in Kennedy’s disease. Funct Integr Genomics. 2019;19:533–9.

    Article  Google Scholar 

  12. Viggiano E, Ergoli M, Picillo E, Politano L. Determining the role of skewed X-chromosome inactivation in developing muscle symptoms in carriers of Duchenne muscular dystrophy. Hum Genet. 2016;135:685–98.

    Article  CAS  Google Scholar 

  13. Sarparanta J, Jonson PH, Golzio C, Sandell S, Luque H, Screen M, et al. Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy. Nat Genet. 2012;44:450–5. S1-2

    Article  CAS  Google Scholar 

  14. Hashizume A, Fischbeck KH, Pennuto M, Fratta P, Katsuno M. Disease mechanism, biomarker and therapeutics for spinal and bulbar muscular atrophy (SBMA). J Neurol Neurosurg Psychiatry. 2020;91:1085–91.

    Article  Google Scholar 

  15. Chivet M, Marchioretti C, Pirazzini M, Piol D, Scaramuzzino C, Polanco MJ, et al. Polyglutamine-expanded androgen receptor alteration of skeletal muscle homeostasis and myonuclear aggregation are affected by sex, age and muscle metabolism. Cells. 2020;9:325.

  16. Migeon BR. X-linked diseases: susceptible females. Genet Med. 2020;22:1156–74.

    Article  CAS  Google Scholar 

  17. Soraru G, D’Ascenzo C, Polo A, Palmieri A, Baggio L, Vergani L, et al. Spinal and bulbar muscular atrophy: skeletal muscle pathology in male patients and heterozygous females. J Neurol Sci. 2008;264:100–5.

    Article  CAS  Google Scholar 

Download references


The authors would like to express sincere gratitude to the patient and family for their cooperation in this study. Furthermore, this work was supported by Youth Innovation Fund in Neurology.

Author information

Authors and Affiliations


Corresponding authors

Correspondence to Dong Zhang or Pengfei Lin.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

This study was conducted according to the Declaration of Helsinki and was approved by the Ethics Committee of the Cheeloo College of Medicine, Shandong University. The patient and her family members provided written informed consent for genetic analysis, muscle biopsy, and publication of this report.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Xu, L., Geng, H., Lv, X. et al. A female carrier of spinal and bulbar muscular atrophy diagnosed with DNAJB6-related distal myopathy. J Hum Genet 67, 441–444 (2022).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


Quick links