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Open Access 01-09-2020 | Original Communication

A novel frameshift deletion in autosomal recessive SBF1-related syndromic neuropathy with necklace fibres

Authors: Qiang Gang, Conceição Bettencourt, Janice Holton, Christopher Lovejoy, Viorica Chelban, Emer Oconnor, Yun Yuan, Mary M. Reilly, Michael Hanna, Henry Houlden

Published in: Journal of Neurology | Issue 9/2020

Abstract

Objective

To identify the genetic cause of complex neuropathy in two siblings from a consanguineous family.

Methods

The patients were recruited from our clinic. Muscle biopsy and whole-exome sequencing (WES) were performed. Fibroblasts cell lines from the index patient, unaffected parents, and three normal controls were used for cDNA analysis and western blot.

Results

The index patient was a 29-year-old male with clinical phenotype of syndactyly, pes cavus, swallowing difficulties, vision problem, imbalance, and muscle weakness. The sibling had similar, but milder symptoms. Nerve conduction studies and electromyography of both patients suggested sensory-motor axonal neuropathy. Muscle biopsy showed a feature of necklace fibres. WES identified a novel homozygous frameshift deletion (c.5477-5478del; p.1826-1826del) in exon 40 of the SBF1 gene in the two siblings, while both parents and the unaffected sibling were heterozygous carriers. Functional analysis showed a markedly reduced level of MTMR5 protein encoded by SBF1 in the index case. The levels of MTMR5 protein in unaffected parents were similar to those found in controls.

Conclusion

A novel homozygous frameshift deletion in SBF1 was identified in this family. Sensory-motor axonal neuropathy and necklace fibres in biopsy were the major features expanding the phenotypic spectrum of SBF1-related recessive syndromic neuropathy.

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Title: A novel frameshift deletion in autosomal recessive SBF1-related syndromic neuropathy with necklace fibres
Authors: Qiang Gang
Conceição Bettencourt
Janice Holton
Christopher Lovejoy
Viorica Chelban
Emer Oconnor
Yun Yuan
Mary M. Reilly
Michael Hanna
Henry Houlden
Publication date: 01-09-2020
Publisher: Springer Berlin Heidelberg
Published in: Journal of Neurology / Issue 9/2020
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-020-09827-y

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

A novel frameshift deletion in autosomal recessive SBF1-related syndromic neuropathy with necklace fibres

Abstract

Objective

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Objective

Methods

Results

Conclusion

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