Table 1.
Mutations in and Clinical Findings for Individuals with DA8
|
Family A |
Family B |
Family C |
Family D |
|||||||
|---|---|---|---|---|---|---|---|---|---|---|
| III-1 | III-2 | II-2 | III-2 | II-1 | III-5a | IV-3 | V-2 | II-1 | I-1 | |
| Mutation Information | ||||||||||
| MYH3 exon | 25 | 25 | 25 | 25 | 25 | 8 | 8 | 8 | no mutation identified | no mutation identified |
| cDNA change | c.3214_3216dup | c.3214_3216dup | c.3214_3216dup | c.3224A>C | c.3224A>C | c.727_729del | c.727_729del | c.727_729del | NA | NA |
| Predicted protein alteration | p.Asn1072dup | p.Asn1072dup | p.Asn1072dup | p.Gln1075Pro | p.Gln1075Pro | p.Ser243del | p.Ser243del | p.Ser243del | NA | NA |
| GERP score | 5.64 | 5.64 | 5.64 | 5.64 | 5.64 | 4.94 | 4.94 | 4.94 | NA | NA |
| CADD score v.1.1 (phred-like) | 17.62 | 17.62 | 17.62 | 20.8 | 20.8 | 18.47 | 18.47 | 18.47 | NA | NA |
| PolyPhen-2 score (HumVar) | NA | NA | NA | 0.931 | 0.931 | NA | NA | NA | NA | NA |
| Clinical Features: Face | ||||||||||
| Downslanting palpebral fissures | + | + | + | + | + | ND | − | − | + | + |
| Ptosis | − | + | − | + | + | ND | − | − | + | + |
| Long nasal bridge | + | + | + | + | + | ND | − | − | + | + |
| Low-set, posteriorly rotated ears | − | − | − | + | + | ND | + | + | + | + |
| Clinical Features: Limbs | ||||||||||
| Hypoplastic flexion creases | + | + | + | + | + | ND | + | + | + | + |
| Camptodactyly | + | + | + | + | + | ND | + | + | + | + |
| Antecubital webbing | − | − | − | − | + | ND | − | + | − | − |
| Elbow contractures | + | + | + | + | + | ND | − | + | − | − |
| Limited forearm supination | + | + | + | ND | + | ND | ND | ND | + | + |
| Hip contractures | ND | ND | ND | ND | + | ND | − | ND | + | − |
| Knee contractures | − | + | + | + | + | + | + | + | − | − |
| Popliteal webbing | − | + | + | ND | + | ND | + | + | − | − |
| Foot contractures | − | − | − | − | metatarsus adductus | ND | limited ankle dorsiflexion | − | clubfeet | − |
| Other Clinical Features | ||||||||||
| Scoliosis | + | + | − | + | + | + | + | + | + | − |
| Short neck | + | + | + | + | + | + | + | + | + | + |
| Neck webbing | − | + | + | + | + | ND | + | + | + | + |
| Short stature | + | + | − | + (<3rd percentile) | + (<5th percentile) | + | + | ND | + | + |
| Vertebral fusion | C1–C2 | T10–L3 | − | ND | ND | C1-C2 | multiple | multiple | − | − |
| Other | webbing of fingers | NA | NA | NA | mild cervical spinal stenosis | craniosynostosis | cleft palate, craniosynostosis |
bilateral inguinal hernia, spondylolisthesis |
VSD | VSD |
This table provides a summary of clinical features of affected individuals from families in whom MYH3 mutations causing DA8 were identified and one family in whom no mutation was identified. Clinical characteristics listed in the table are primarily features that delineate DA8. cDNA positions in MYH3 (GenBank: NM_002470.3) are provided as named by the HGVS MutNomen web tool. Abbreviations are as follows: +, presence of a finding; −, absence of a finding; ND, no data; NA, not applicable; GERP, genomic evolutionary rate profiling; CADD, combined annotation-dependent depletion; VSD, ventricular septal defect.
a
Described on the basis of a clinician’s report.