Table 1 Presenting clinical features and details of variants identified
From: The role of exome sequencing in childhood interstitial or diffuse lung disease
Patient | 1 | 2 | 3 | 4 | 5 | 6 |
|---|---|---|---|---|---|---|
Gender | M | F | F | M | F | F |
Decimal age (years) | 0.33 | 1.50 | 0.15 | 0.13 | 0.16 | 0.61 |
Gestation (wks) | 41 | 37 | 34 + 1 | 38 | 40 + 6 | 39 |
Neonatal respiratory distress | − | − | + | + | + | − |
Gene | RFXANK (OMIM#603200) | CTCF (OMIM#604167) | RPL15 (OMIM#604174) | RARB (OMIM#180220) | TBX4 (OMIM#601719) | VIP (OMIM#192320) |
Condition | MHC class II deficiency, complementation group B (OMIM#209920) | Mental retardation, autosomal dominant 21 (OMIM#615502) | Diamond–Blackfan anaemia 12 (OMIM#615550) | Syndromic microphthalmia-12 (OMIM#615524) | Ischiocoxopodopatellar syndrome with or without pulmonary arterial hypertension (OMIM#147891) |  |
Variant | NM_003721.3 c.634C > T p.(Arg212*) Bi-parentally inherited SCV001763560.1 | NM_006565) c.1699C > T p.(Arg567Trp) De novo SCV001763559.1 | NM_002948.3 c.314G > T p.(Arg105Leu) De novo SCV001244976.1 | NM_000965.4 c.835 T > G p.(Phe279Val) De novo SCV001245030.1 | NM_018488.3 c.292C > G p.[(Pro98Ala)] Maternally inherited SUB10133140 | NM_003381.3 c[107 + 1G > C] [ =]p.[?]) De novo Novel gene |
Interpretation | Pathogenic | Pathogenic | Likely pathogenic | Likely pathogenic | Likely pathogenic | Variant of uncertain significance |
Inheritance | Autosomal recessive | Autosomal dominant | Autosomal dominant | Autosomal dominant | Autosomal dominant | Autosomal dominant |
Clinical | ||||||
Tachypnoea | + | − | + | + | + | + |
Dyspnoea at rest | + | − | + | + | + | + |
Cough | − | + | n/a | n/a | − | − |
Hypoxia | + | − | + | + | + | + |
Wheeze | − | + | n/a | n/a | − | − |
Crackles | − | + | n/a | n/a | − | − |
Recurrent infections | − | + | n/a | n/a | − | − |
Pulmonary arterial hypertension | − | − | + | + | + | − |
CT-chest | Ground glass changes | Air-trapping in bilateral posterior lower lobes. Posterior bilateral patchy collapse, minor bronchiectasis in bilateral lower zones | n/a | Interstitial changes | Ground glass changes | Ground glass changes |
Echocardio-gram | + | − | Pulmonary stenosis | n/a | Pulmonary arterial hypertension, patent ductus arteriosus, small atrial septal defect/patent foramen ovale | − |
Broncho-alveolar lavage | +Human rhinovirus | − | n/a | n/a | − | − |
Biopsy | + | − | n/a | n/a | − | − |
Other phenotypic features | Low IgA, IgM, IgG, T and B subsets Low pneumococcal, Haemophilus influenzae and diphtheria serology | Failure to thrive and gross motor delay | Intrauterine growth restriction, pulmonary stenosis, distinctive facial features (depressed nasal bridge, anteverted nares, long philtrum, narrow mouth, micrognathia), bilateral single transverse palmar crease | Diaphragmatic eventration, distinctive facial features, microphthalmia on MRI | Neonatal pneumothoraces CT angiogram demonstrated a large main pulmonary artery with hypoplastic pulmonary branch arteries consistent with PAH | Failure to thrive |