Table 1.
Identification of rare, pathogenic ASPH variants in four families with EHI/MHS.
| Variant name | V54A | K88T | D149H | K202R |
|---|---|---|---|---|
| Chr | 8 | 8 | 8 | 8 |
| Position (GRCh 37) | 62596603 | 62580807 | 62577998 | 62577838 |
| Ref | A | T | C | T |
| Allele | G | G | G | C |
| Consequence | missense_variant | missense_variant | missense_variant | missense_variant |
| SYMBOL | ASPH | ASPH | ASPH | ASPH |
| CDS_position | 161 | 263 | 445 | 605 |
| Exon | 2 | 4 | 5 | 5 |
| Protein_position | 54 | 88 | 149 | 202 |
| Amino_acids | V/A | K/T | D/H | K/R |
| Codons | gTt/gCt | aAa/aCa | Gac/Cac | aAg/aGg |
| Existing_variation | rs779765042 | – | rs1236122813 | rs145678786, COSV100727527 |
| gnomAD_AF | 0.0001076 | – | 0.00001924 | 0.0008436 |
| SIFT | deleterious(0.01) | tolerated(0.07) | deleterious(0.04) | deleterious_low_confidence(0) |
| PolyPhen | probably_damaging(0.996) | probably_damaging(0.976) | possibly_damaging(0.824) | benign(0.084) |
| CADD_PHRED | 27.9 | 22.5 | 16.1 | 9.921 |
| Clinical diagnosis | MHS/EHI | EHS | MHS/EHI | EHS |
| Contracture test | CHCT | IVCT | CHCT | IVCT |
| Caffeine | 0.4*(proband), 0.8*(sister) | 0 g | 0.6* | 0 g |
| Halothane | 1.4**(proband), 1.0**(sister) | 0.05 g | 4.0** | 0.1 g |
The threshold responses for a positive diagnosis in CHCT were *caffeine >0.3 and/or **halothane >0.7. The threshold for a positive diagnosis in IVCT were 0.2 g force produced at 2 mM caffeine and/or at 2%.