Page 140 - AN-3-3

Advanced Neurology Rare manifestation in nemaline myopathy

It is important to note that lower, but not upper, motor the same family. To account for the absence of clinical
10
neuron impairment has been documented in nemaline manifestations in the patient’s sister, we speculate that she
myopathy. The reason for the pyramidal tract impairment has not yet reached the age of onset. Genetic compensation
7
in our patient requires advanced research. The uncommon could be another plausible reason, potentially resulting in
clinical manifestations, previously unseen, represent a a milder disease phenotype. This process might explain
11
novel phenotype of nemaline myopathy. Similar cases why the patient’s sister was asymptomatic, as genetic
need to be distinguished from spinal and bulbar muscular compensatory responses could mask the phenotypic effect
atrophy, amyotrophic lateral sclerosis, and spinal muscular of deleterious alleles.
atrophy. For patients presenting with limb weakness since
childhood, delayed motor milestones, pyramidal tract 4. Conclusion
impairment, a long medical history, and normal creatine Nemaline myopathy has a broad spectrum of clinical
kinase levels, early completion of muscle biopsy and phenotypes but is rarely accompanied by abnormalities
genetic testing is essential to prevent misdiagnosis and such as pyramidal tract impairment, high arches, and
ineffective treatment. oligospermia. To achieve a clear diagnosis, muscle biopsies
Nemaline myopathy is associated with at least 12 genes, and genetic testing should be conducted.
including NEB, ACTA1, TPM3, TPM2, TNNT1, TNNT3,
and MYPN genes, which encode proteins involved in the Acknowledgments
structural organization and regulation of thin filaments. None.
2
The NEB gene mutation is the most prevalent in nemaline
myopathy. The NEB gene encodes the sarcomeric protein Funding
nebulin, which is important to thin-filament length None.
regulation and stability, force production, and alignment of
myofibrils. At present, the mechanism of muscle weakness Conflict of interest
8
and atrophy remains unclear. The patient harbors two
variants in the NEB gene: c.21522+3A>G and c.23455A>T. The authors declare that they have no competing interests.
The frequency of the c.21522+3A>G variant in the genome Author contributions
aggregation (gnomAD) database of normal individuals
from Eastern Asian populations is 0.002201. Function Conceptualization: Yuxin Liu, Sheng Yao, Yun Yuan,
experimental research has shown that this variant would Chenjing Sun
induce the aberrant splicing of mRNA. Other pathogenic Formal analysis: Yuxin Liu, Chenjing Sun
2
mutations in transpositions detected in at least four Investigation: Yuxin Liu, Shengyang Liu
probands manifesting similar clinical phenotypes have Methodology: Yuxin Liu, Xiaokun Qi
been reported in the literature. A pathogenic variant was Writing – original draft: Yuxin Liu
2,9
determined according to the latest edition of the standards Writing – review & editing: Yuxin Liu, Chenjing Sun
and guidelines for the interpretation of genetic variation
issued by the American College of Medical Genetics Ethics approval and consent to participate
(ACMG). The frequency of the c.23455A>T variant in the Not applicable.
gnomAD database of normal individuals from Eastern
Asian populations is 0, and it has never been reported. The Consent for publication
nonsense mutation in the NEB gene, which is associated The written informed consent of the patient for publication
with a loss-of-function pathogenic mechanism, may drive has been obtained.
the pathogenesis of nemaline myopathy. Our patient was
found to carry pathogenic variants in the transpositions. Availability of data
Therefore, the c.23455A>T variant was identified as a
pathogenic variant according to the ACMG guidelines. Not applicable.
The family verification results revealed that these two NEB References
heterozygous variants were inherited from the patient’s
parents, respectively, and his sisters also carried a similar 1. Shy GM, Engel WK, Somers JE, Wanko T. Nemaline
set of variants but presented with none of the clinical myopathy. A new congenital myopathy. Brain. 1963;
manifestations. 86(4):793-810.
A report has shown that the same mutation in the NEB doi: 10.1093/brain/86.4.793
gene could lead to different manifestations in members of 2. Yin X, Pu C, Wang Z, Li K, Wang H. Clinico-pathological

Volume 3 Issue 3 (2024) 4 doi: 10.36922/an.3171