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Brain Dev. 2018 Apr;40(4):343-347. doi: 10.1016/j.braindev.2017.12.001. Epub 2017 Dec 19.

Novel BICD2 mutation in a Japanese family with autosomal dominant lower extremity-predominant spinal muscular atrophy-2.

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Department of Pediatric Neurology, Kobe City Pediatric and General Rehabilitation Center for the Challenged, Kobe, Japan. Electronic address:
Department of Clinical Genetics, Hyogo Prefectural Kobe Children's Hospital, Kobe, Japan; Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
Department of Neurology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Japan.
Department of Neurology, Kobe City Medical Center General Hospital, Kobe, Japan.
Department of Community Medicine and Social Healthcare Science, Kobe University Graduate School of Medicine, Kobe, Japan.
Department of Pediatrics, Hyogo College of Medicine, Nishinomiya, Japan.
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.



The most common form of spinal muscular atrophy (SMA) is a recessive disorder caused by SMN1 mutations in 5q13, whereas the genetic etiologies of non-5q SMA are very heterogenous and largely remain to be elucidated. We present a father and son with atrophy and weakness of the lower leg muscles since infancy. Genetic studies in this family revealed a novel BICD2 mutation causing autosomal dominant lower extremity-predominant SMA type 2.


The proband was the father, aged 30, and the son was aged 3. Both of them were born uneventfully to nonconsanguineous parents. While the father first walked at the age of 19 months, the son was unable to walk at age 3 years. In both, knee and ankle reflexes were absent and sensation was intact. Serum creatine kinase levels were normal. The son showed congenital arthrogryposis and underwent orthopedic corrections for talipes calcaneovalgus. Investigation of the father at the age of 5 years revealed normal results on nerve conduction studies and sural nerve biopsy. Electromyography showed chronic neurogenic change, and muscle biopsy showed features suggestive of denervation. The father was diagnosed clinically with a sporadic distal SMA. Follow-up studies showed very slow progression.


Next-generation and Sanger sequencing revealed a deleterious mutation in BICD2: c.1667A>G, p.Tyr556Cys, in this family.


BICD2 is a cytoplasmic conserved motor-adaptor protein involved in anterograde and retrograde transport along the microtubules. Next-generation sequencing will further clarify the genetic basis of non-5q SMA.


Autosomal dominant lower extremity-predominant spinal muscular atrophy type 2; BICD2 mutation; Motor-adaptor protein; Next-generation sequencing; Non-5q spinal muscular atrophy; SMN1 in 5q13; Spinal muscular atrophy

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