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

Fig. 1. Clinical information and functional variant validation for families 1–3.

Fig. 1

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].