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. 2021 Sep;29(9):1332-1336.
doi: 10.1038/s41431-021-00901-1. Epub 2021 May 10.

Solving unsolved rare neurological diseases-a Solve-RD viewpoint

Rebecca Schüle  1   2   3 , Dagmar Timmann  4 , Corrie E Erasmus  5 , Jennifer Reichbauer  6   7 , Melanie Wayand  6   7 ; Solve-RD-DITF-RND; Bart van de Warrenburg  8   9 , Ludger Schöls  6   7   8 , Carlo Wilke  6   7 , Andrea Bevot  10 , Stephan Zuchner  11 , Sergi Beltran  12   13   14 , Steven Laurie  12 , Leslie Matalonga  12 , Holm Graessner #  8   15 , Matthis Synofzik #  6   7   8 ; Solve-RD Consortium
Collaborators, Affiliations

Solving unsolved rare neurological diseases-a Solve-RD viewpoint

Rebecca Schüle et al. Eur J Hum Genet. 2021 Sep.

Erratum in

  • Correction: Solving unsolved rare neurological diseases-a Solve-RD viewpoint.
    Schüle R, Timmann D, Erasmus CE, Reichbauer J, Wayand M; Solve-RD-DITF-RND; van de Warrenburg B, Schöls L, Wilke C, Bevot A, Zuchner S, Beltran S, Laurie S, Matalonga L, Graessner H, Synofzik M; Solve-RD Consortium. Schüle R, et al. Eur J Hum Genet. 2021 Sep;29(9):1462-1465. doi: 10.1038/s41431-021-00935-5. Eur J Hum Genet. 2021. PMID: 34429526 Free PMC article. No abstract available.
No abstract available

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Conflict of interest statement

HG receives/has received research support from the Deutsche Forschungsgemeinschaft (DFG), the Bundesministerium für Bildung und Forschung (BMBF), the Bundesministerium für Gesundheit (BMG) and the European Union (EU). He has received consulting fees from Roche. He has received a speaker honorarium from Takeda. The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Clinical information and functional variant validation for families 1–3.
A Pedigrees and cranial MRI of patient 1 (NM_001168272.1(ITPR1):c.805C>T, p.(Arg269Trp)). Mid-sagital MRI (T2) shows marked cerebellar atrophy at age 7. B Pedigree and longitudinal MRIs taken from patient 2 (pontocerebellar atrophy—NM_016042.3(EXOSC3):c.395A>C, p.(Asp132Ala)). MRIs demonstrate marked cerebellar atrophy while brainstem volume is not affected. C Pedigree, segregation analysis and functional analysis in family 3. The index cases carries two intronic POLR3A variants. Variant c.1048+5G>T is located in intron 7; RT-PCR with primers binding to sequences in exon (forward) and exon 9 (reverse) demonstrate presence of an aberrant transcript that is absent in controls. Specific amplification of this additional band and sequencing revealed that all 177 bp of intron 7 are included in the transcript. A nonsense codon in intron 7 presumably leads to termination of translation (p.Phe352_Arg353ins(23)Ter). The variant c.1909+22C>T has previously been demonstrated to lead to inclusion of the first 19 nucleotides from intron 14 into the final transcript und consequently to shift of the reading frame [8].
See this image and copyright information in PMC

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