Genome sequencing uncovers phenocopies in primary progressive multiple sclerosis

Abstract

This study provides evidence to support the hypothesis that rare Mendelian genetic variants contribute to the risk for developing progressive forms of MS. Ann Neurol 2018;83:51-63.

Familial multiple sclerosis patients have a shorter delay in diagnosis than sporadic cases

“…To compensate for this, several symptoms/signs are reported as "red flags" for when to consider differential diagnoses 21 . Based on the fact that MS families occasionally are found to have an inherited neurological disorder mimicking MS 24,27,34 and the present findings in this study of familial MS cases being diagnosed faster than sporadic cases, we suggest that "family history" might be a "red flag" for considering genetic differential diagnosis. The above factors all add to our knowledge on the question of benefits from a fast diagnosis compared to consequences of a misdiagnosis 35…”

“…Inherited disorders do also contribute to the misdiagnoses. Based on numerous case reports of simplex MS families [24][25][26] and studies on sporadic and familial MS populations 27 there are several examples of MS cases found to have a genetic disorder mimicking MS.…”

Multiple sclerosis – a review

“…Recent work has uncovered genetic differences between relapsing–remitting MS (RRMS) and primary progressive MS (PPMS) not previously detected in genome‐wide association studies, most probably due to the under‐representation of PPMS in these cohorts. Genetic variants associated with other progressive neurological disorders are relatively over‐represented in progressive MS . Similar genetic risk exists when all MS‐associated alleles are taken into account, indicating additional risk for progressive disease superimposed on underlying genetic susceptibility.…”

A gene expression signature‐based nomogram model in prediction of breast cancer bone metastases

“…32,33 REEP1 protein, which is preferentially expressed in neuronal and neuronal-like exocytotic tissues like brain, spinal cord, and testes and localized to endoplasmic reticulum (ER) and plasma membranes, is a member of a family of ER shaping proteins. 34,35 It has been found that REEP1 could facilitate mitochondrial-ER interactions, which may result in intracellular Ca 2+ overload and axonal damage, 36 and REEP1 variants were recognized as causes of Neurological Disease like hereditary spastic paraplegia (HSP) and distal hereditary motor neuropathy (dHMN). 37 The third gene SPIB, encoding an ETS-domain transcription factor, was believed to be associated with cancers especially in lymphomas.…”