Yonsei Med J.  2018 Jul;59(5):698-701. 10.3349/ymj.2018.59.5.698.

Two Korean Families with Limb-Girdle Muscular Dystrophy Type 1D Associated with DNAJB6 Mutations

• Kim K
• Park HJ
• Lee JH
• Hong J
• Ahn SW
• Choi YC

• KMID: 2412662
• DOI: http://doi.org/10.3349/ymj.2018.59.5.698

Abstract

Limb-girdle muscular dystrophies (LGMD) are heterogeneous disorders with autosomal inheritance. Autosomal dominant LGMD mapped to 7q36.3 has been classified as LGMD type 1D (LGMD1D) in the Human Gene Nomenclature Committee Database. LGMD1D is characterized predominantly by limb-girdle weakness and may also show a bulbar symptom in some cases. In the past, the frequency of this disease was uncommon, and this disorder was mainly found in Europe and the United States. However, recently, this disorder has been reported in Asia, including Japan, Korea, and Taiwan. Here, we report on three LGMD1D patients, including one with a novel mutation in DNAJB6, c.298T>A. While two patients complained of limb-girdle weakness, as would be expected, one patient had distal weakness. They had various serum creatine kinase levels. Radiologic findings in one patient showed fatty degeneration and atrophy in the posterior part of distal muscles. Pathologic findings in one of the patients showed rimmed vacuoles. Although LGMD1D is still uncommon in Korea, we discovered three Korean patients with LGMD1D, including one novel mutation in DNAJB6, p.Phe100Ile (c.298T>A).

Keyword

LGMD1D; DNAJB6; myopathy

MeSH Terms

Asia
Atrophy
Creatine Kinase
Europe
Humans
Japan
Korea
Muscles
Muscular Diseases
Muscular Dystrophies, Limb-Girdle*
Taiwan
United States
Vacuoles
Wills
Creatine Kinase

Figure

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  Fig. 1 Radiologic and pathologic findings of muscular dystrophy patients. (A) Radiologic finding of patient 1. T2-weighted MRI shows moderate fatty change in the tibialis posterior (arrowhead) and gastrocnemius (arrow). (B) Muscle biopsy in patient 3 shows rimmed vacuole findings (arrow) (hematoxylin and eosin stain, ×200), scale bar, 50 µm.

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  Fig. 2 Pedigree and electropherogram findings of three limb-girdle muscular dystrophy type 1D patients. (A) Pedigree of patient 1. (B) Electropherogram presents a mutation in DNAJB6 genomic DNA (c.265T>A; p.Phe89Ile). (C) Novel mutation in patient 2 and his father (his mother's sequencing showed no variant in DNAJB6).

Reference

1. Iyadurai SJ, Kissel JT. The limb-girdle muscular dystrophies and the dystrophinopathies. Continuum (Minneap Minn). 2016; 22:1954–1977.

2. 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; 71:407–416.

3. Ruggieri A, Brancati F, Zanotti S, Maggi L, Pasanisi MB, Saredi S, et al. Complete loss of the DNAJB6 G/F domain and novel missense mutations cause distal-onset DNAJB6 myopathy. Acta Neuropathol Commun. 2015; 3:44.

4. 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; 24:431–435.

5. 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; 44:450–455.

6. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, 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; 17:405–424.

7. Palmio J, Jonson PH, Evilä A, Auranen M, Straub V, Bushby K, et al. Novel mutations in DNAJB6 gene cause a very severe early-onset limb-girdle muscular dystrophy 1D disease. Neuromuscul Disord. 2015; 25:835–842.

8. Sato T, Hayashi YK, Oya Y, Kondo T, Sugie K, Kaneda D, et al. DNAJB6 myopathy in an Asian cohort and cytoplasmic/nuclear inclusions. Neuromuscul Disord. 2013; 23:269–276.

9. Nam TS, Li W, Heo SH, Lee KH, Cho A, Shin JH, et al. A novel mutation in DNAJB6, p.(Phe91Leu), in childhood-onset LGMD1D with a severe phenotype. Neuromuscul Disord. 2015; 25:843–851.

10. Tsai PC, Tsai YS, Soong BW, Huang YH, Wu HT, Chen YH, et al. A novel DNAJB6 mutation causes dominantly inherited distal-onset myopathy and compromises DNAJB6 function. Clin Genet. 2017; 92:150–157.