Table 1 The evolution of diagnostic yield; 31 novel genetic diagnoses after 5Â years of systematic follow-up
Patient IDa | Gender | Â | Variant in VCF 2015 | Gene in panel 2015 | Â | This study | Initial analysis 2015a | ||
|---|---|---|---|---|---|---|---|---|---|
Gene | Step | Identified by | Note | Result | Gene | ||||
6 | F | HNRNPK | Yes | No | 1 | Variant reclassification (new disease-gene) | OMIM: 616580 | Possible | HNRNPK |
32 | F | CSNK2A1 | Yes | No | 1 | Variant reclassification (new disease-gene) | OMIM: 617062 | Possible | CSNK2A1 |
40 | F | ADPRHL2 | Yes | No | 1 | Variant reclassification (new disease-gene) | OMIM: 618170 | Possible | ADPRHL2 |
46 | M | DHX30 | Yes | No | 1 | Variant reclassification (new disease-gene) | OMIM: 617804 | Possible | DHX30 |
48 | M | CSNK2B | Yes | No | 3 | Variant reclassification (new disease-gene) | OMIM: 618732 | Possible | CSNK2B |
84 | M | c19orf12 | Yes | No | 1 | Variant reclassification (new disease-gene) | OMIM: 614298 | Possible | C19orf12 |
104 | F | PPP2CA | Yes | No | 1 | Variant reclassification (new disease-gene) | OMIM: 618354 | Possible | PPP2CA |
109 | M | KAT8 | Yes | No | 3 | Variant reclassification (new disease-gene) | OMIM: 618974 | Possible | KAT8 |
112 | M | SNORD118 | Yes | No | 1 | Variant reclassification (new disease-gene) | OMIM: 614561 | Possible | SNORD118 |
93 | M | TBC1D24 | Yes | Yes | 3 | Variant reclassification (additional disease-gene) | PMID: 31257402 | Possible | TBC1D24 |
34 | M | HSD17B10 | Yes | Yes | 1 | Variant reclassification (additional testing) | Metabolic investigation | Possible | HSD17B1 |
103 | M | ACSL4 | Yes | Yes | 1 | Variant reclassification (additional testing) | Mother de novo | Possible | ACSL4 |
147 | F | PIK3R2 | Yes | Yes | 1 | Reanalysis (additional testing) | Segregation in affected brother | Possible (other) | DHCR24 |
138 | M | NAA15 | Yes | No | 1 | Update pipeline (gene panel-new) | OMIM: 617787 | No cause | – |
129 | F | SRCAP | Yes | Yes | 3 | Update pipeline (gene panel-additional); variant reclassification (additional disease-gene) | PMID: 33909990 | No cause | – |
113 | M | NALCN | Yes | Yes | 2 | Update pipeline (gene panel-additional) | OMIM: 616266 | Possible (other) | PRPF40B |
58 | F | SLC6A1 | Yes | Yes | 1 | Update pipeline (CNV) | - | Possible (other) | HOXD3 |
143 | M | FOXP1 | Yes | Yes | 2 | Update pipeline (SNV); reanalysis (additional testing) | Intronic (+ 26) loss of branchpoint; splicedefect confirmed on RNA | No cause | – |
53 | F | ANKRD11 | No | Yes | 2 | Update pipeline (quality parameters) | 3/7 reads (<# reads)b | No cause | – |
105 | M | ANKRD11 | Yes | Yes | 2 | Update pipeline (quality parameters) | 16/31 reads (low quality) | No cause | – |
140 | F | TSC1 | No | Yes | 1 | Update pipeline (quality parameters) | 21/123 (<%variant reads)b | No cause | – |
26 | M | EP300 | Yes | Yes | 3 | Update pipeline (quality parameters) | 10/78 reads (<%variant reads) | Possible (other) | ZNF41 |
3 | M | PRPS1 | No | No | 1 | Resequencing; variant reclassification (HGMD) | PMID: 31434166 | No cause | – |
7 | F | LAMA1 | No; yes | No | 1 | Resequencing | - | No cause | – |
9 | F | ARX | No | Yes | 1 | Resequencing | - | No cause | – |
24 | M | PAK1 | No | No | 3 | Resequencing | - | No cause | – |
36 | F | SATB2 | No | Yes | 1 | Resequencing | - | No cause | – |
79 | F | NUS1 | No | No | 3 | Resequencing | - | No cause | – |
14 | F | NSUN2 | No | No | 3 | Resequencing | - | Possible (other) | several |
28 | F | KMT2B | No | No | 1 | Resequencing | - | Possible (other) | PNPLA6 |
47 | M | KMT2D | No | Yes | 3 | Resequencing | - | Possible (other) | ZNF711 |