Two Japanese Patients With SMA Type 1 Suggest that Axonal-SMN May Not Modify the Disease Severity.

Abstract

BACKGROUND:

Spinal muscular atrophy is caused by survival motor neuron gene SMN1 mutations. SMN1 produces a full-length SMN1 protein isoform encoded by exons 1-7, and an axonal-SMN protein isoform encoded by exons 1-3 and intron 3. The axonal-SMN protein is expressed only in the embryonic period and plays a significant role in axonal growth. However, there has been no report on contribution of axonal-SMN to spinal muscular atrophy severity until now.

PATIENTS:

Two Japanese boys with spinal muscular atrophy type 1 in our study presented with generalized muscle weakness and respiratory insufficiency soon after birth and required an artificial ventilator from early infancy. Patient 1 was compound heterozygous for two SMN1 mutations, whole-gene deletion, and an intragenic mutation (c.819_820insT). He retained one copy of SMN1 producing the N-terminal part of SMN1 including axonal-SMN. On the other hand, patient 2 was homozygous for SMN1 deletion. Both of them showed the same copy number of spinal muscular atrophy-modifying genes, NAIP and SMN2. These findings suggested that the C-terminal domain of full-length SMN1 determined the severity, irrespective of presence or absence of axonal-SMN expression.

CONCLUSION:

In patient 1, the C-terminal domain of full-length SMN1 determined spinal muscular atrophy severity, rather than the axonal-SMN, one copy of which could be present and intact. The presence or absence of axonal-SMN may not impact disease severity in spinal muscular atrophy type 1 patients.

• Authors: Hiroyuki Yamada, Yoshinobu Nishida, Toshiro Maihara, Nihayatus Sa'adah, Nur Imma Fatimah Harahap, Dian Kesumapramudya Nurputra, Mawaddah Ar Rochmah, Noriyuki Nishimura, Toshio Saito, Yuji Kubo, Kayoko Saito, Hisahide Nishio
• Journal: Pediatric neurology (Pediatr Neurol) Vol. 52 Issue 6 Pg. 638-41 (Jun 2015) ISSN: 1873-5150 [Electronic] United States
• PMID: 25838041 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• SMN1 protein, human
• Survival of Motor Neuron 1 Protein

Topics

• Axons (metabolism)
• Child
• DNA Mutational Analysis
• Exons
• Humans
• Infant
• Male
• Mutation
• Severity of Illness Index
• Spinal Muscular Atrophies of Childhood (diagnosis, genetics, metabolism)
• Survival of Motor Neuron 1 Protein (genetics)