Table 4.
Genetic testing results from 100,000 Genomes Project whole genome sequencing, clinical history and PCD diagnostic test results for each proband A-E in the Wessex non-CF bronchiectasis cohort found to have results consistent with a diagnosis of PCD
| Anonymised family ID | Genetics | Clinical information | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Gene | Allele 1 [Classification] | Allele 2 [Classification] | PCD Diagnosis | Clinical History | nNO (nL/min) | HSV-brushing | HSV-postALI | TEM | IF | |
| A | DNAH5 | DNAH5 GRCh38 5:13780960C > A,NM_001369.3:c.8821-1C > A [Pathogenic] | DNAH5 GRCh38 5:13753289GA > G, NM_001369.3:10815del, p.D3605fs1 [Pathogenic] | Confirmed | Normal situs, no NRDS, persistent wet cough since birth, lower lobectomy age 10y, bronchiectasis, rhinitis since birth, no ear issues | 30 | Static | Static | ODA | DNAH5 absent |
| B | DNAI1 | DNAI1 GrCh38 9:34514436G > A, NM_012144.4:c.1612G > A, p.A538T [Likely Pathogenic] | Homozygous | Confirmed | SI, NRDS, Rhinitis, bronchiectasis, glue ear | 2 | Mostly static | Not done | ODA | Not done |
| C | RPGR | RPGR GRCh38 X:38317333 T > C NM_000328.3:c.602A > G, p.H201R [VUS] | Hemizygous | Possible | Normal situs, NRDS, persistent wet since early infancy, persistent rhinitis since early, glue ear. NO EYE SYMPTOMS | 18 | mixed length shorter and longer than usual, dyskinetic throughout | Cilia short, dyskinetic throughout | Normal | RPGR absent |
| D | CFAP53 | CFAP53 GRCh38 18:50262051G > A, NM_145020.5:c.238C > T, p.R80X (no parental info) | CFAP53 GRCh38 18:50242969C > A, NM_145020.5:c.1144G > T, p.E382X (no parental info) | Candidate | SI, no NRDS, recurrent chest infections started in adulthood, no ear issues, daily rhinitis | 171 | normal 2014 | |||
| E | CEP164 | CEP164 GRCh38 11:117411859C > T, NM_014956.5:c.4228C > T, p.Q1410X. Paternal | CEP164 GRCh38 11:117387204C > T, NM_014956.5:c.1726C > T, p.R576X. Maternal | Candidate | Accompanied by father, BMI 28 103 kg, PICADAR 4; no NRDS but did have pnumonia as an infant; lifelong cough bronchiectasis, rhinitis | 164 | Reduced amplitude; some cilia long; | Within normal limits | ||
ACMG variant classification for each variant is given in bold
The table provides case ID, gene and variant details (with GRCh38 genomic coordinates) and classification (following ACMG guidelines) and final diagnosis. Clinical information provided includes clinical history, nasal nitric oxide levels (nNO (nL/min)), high-speed video (HSV) microscopy analysis from fresh nasal brushings and afterculture of these cells at air–liquid interface (ALI) transmission electron microscopy (TEM) and immunofluorescence (IF) microscopy findings. SI = Situs inversus, NRDS = neonatal respiratory distress syndrome, ODA = outer dynein arm defect