Table 2.
Cohort phenotypes and genetic variants.
| Subject ID | Sex | Race | Key phenotypes | Clinical diagnosis | Spirometry/plethysmography | Identified gene | Variant classification |
|---|---|---|---|---|---|---|---|
| Subject 1 | F | White | Short ribs, hepatomegaly, increased kidney cortical echogenicity | Short-rib thoracic dysplasia 3 with or without polydactyly (OMIM #613091) |
% Predicted FVC: 0.44 % Predicted FEV1: 0.46 % Predicted FEV1/FVC: 1.04 % Predicted FEF25-75: 60 % Predicted TLC: 0.58 % Predicted RV: 0.96 % Predicted RV/TLC: 1.59 |
DYNC2H1 | Positive |
| Subject 11 | M | White | Short ribs, anemia, bilateral echogenic kidneys | Short-rib thoracic dysplasia 3 with or without polydactyly (OMIM #613091) | – | DYNC2H1 | Positive |
| Subject 14 | M | White | Short ribs, developmental delay | Short-rib thoracic dysplasia 3 with or without polydactyly (OMIM #613091) |
% Predicted FVC: 0.81 % Predicted FEV1: 0.85 % Predicted FEV1/FVC: 1.06 % Predicted FEF25–75: 1.23 % Predicted TLC: 0.8 % Predicted VC: 0.79 % Predicted RV: 0.83 % Predicted RV/TLC: 1.02 |
DYNC2H1 | Positive |
| Subject 21 | M | White | Short ribs, autism, chronic kidney disease | Short-rib thoracic dysplasia 3 with or without polydactyly (OMIM #613091) |
% Predicted FVC: 0.19 % Predicted FEV1: 0.15 % Predicted FEV1/FVC: 0.81 % Predicted FEF25–75: 0.08 % Predicted PEFR: 0.31 % Predicted TLC: 0.64 % Predicted VC: 0.33 % Predicted FRC: 0.8 % Predicted RV: 1.32 % Predicted RV/TLC: 2.06 |
DYNC2H1 | Positive |
| Subject 23 | F | White | Short ribs, hydrocephalus, hydronephrosis, coarse liver echotexture, liver cyst | Short-rib thoracic dysplasia 3 with or without polydactyly (OMIM #613091) | – | DYNC2H1 | Positive |
| Subject 29 | F | Black | Short ribs, ventriculomegaly | Short-rib thoracic dysplasia 3 with or without polydactyly (OMIM #613091) | – | DYNC2H1 | Positive |
| Subject 39 | M | White | Short ribs, elevated aminotransferases and GGT | Short-rib thoracic dysplasia 3 with or without polydactyly (OMIM #613091) | – | DYNC2H1 | Positive |
| Subject 37 | F | White | Thoracolumbar scoliosis, myopia, astigmatism | Congenital Contractural Arachnodactyly (OMIM #121050) | – | FBN2 | Strong candidate |
| Subject 2 | F | Hispanic White | Craniosynostosis, subglottic stenosis, macrocephaly, hydrocephalus, global developmental delay, thoracic scoliosis | Pfeiffer Syndrome (OMIM #101600) | – | FGFR2 | Positive |
| Subject 4 | F | White | Thoracic scoliosis | Larsen syndrome (OMIM #150250) | – | FLNB | Strong candidate |
| Subject 30 | M | White | Tethered cord, hip dysplasia, vertical talus, scoliosis | Larsen syndrome (OMIM #150250) |
% Predicted FVC: 0.77 % Predicted FEV1: 0.84 % Predicted FEV1/FVC: 1.09 % Predicted FEF25-75: 0.86 % Predicted PEFR: 0.71 |
FLNB | Positive |
| Subject 36 | F | Asian | Bilateral talipes equinovarus, bilateral elbow dislocation, left femoral head dislocation, joint contractures | Larsen syndrome (OMIM #150250) |
% Predicted FVC: 0.89 % Predicted FEV1: 0.844 % Predicted FEV1/FVC: 0.99 % Predicted FEF25-75: 1.19 % Predicted PEFR: 1.1 |
FLNB | Positive |
| Subject 16 | M | White | Thoracic scoliosis, global developmental delay, cryptorchidism, chordeic penis | X-linked syndromic mental retardation, turner type (OMIM #309590) | – | HUWE1 | Positive |
| Subject 38 | M | White | Short ribs, retinopathy, bilateral increased kidney echogenicity, decreased corticomedullary differentiation, kidney dysplasia, cortical cyst, dialysis dependence, hydrocephalus | Short-rib thoracic dysplasia 9 with or without polydactyly (OMIM #266920) | – | IFT140 | Positive |
| Subject 27 | F | Black | Short ribs, hypertension, chronic kidney disease, coarse liver, cerebellar volume loss | Joubert syndrome/acrocallosal syndrome (OMIM #200990) | – | KIF7 | Strong candidate |
| Subject 34 | F | Asian | Thoracic scoliosis, rib fusions, vertebral fusions and segmentation defects | Spondylocostal dysostosis 2 (OMIM #608681) |
% Predicted FVC: 0.52 % Predicted FEV1: 0.66 % Predicted FEF25–75: 2.12 % Predicted TLC: 0.6 % Predicted FRC: 0.53 % Predicted RV: 0.4 % Predicted RV/TLC: 0.75 |
MESP2 | Positive |
| Subject 17 | F | Black | Thoracolumbar scoliosis, myopia, pes planus | Freeman–Sheldon syndrome (OMIM #193700) |
% Predicted FVC: 0.66 % Predicted FEV1: 0.63 % Predicted FEV1/FVC: 0.96 % Predicted FEF25–75: 0.83 % Predicted PEFR: 0.69 % Predicted TLC: 0.68 % Predicted VC: 0.7 % Predicted FRC: 0.67 % Predicted RV: 0.63 % Predicted RV/TLC: 0.93 |
MYH3 | Strong candidate |
| Subject 15 | F | Black | Short ribs, retinopathy, lumbar scoliosis, short stature, chronic kidney disease | Short-rib thoracic dysplasia 6 with or without polydactyly (OMIM #263520) |
% Predicted FVC: 0.4 % Predicted FEV1: 0.28 % Predicted FEV1/FVC: 0.72 % Predicted FEF25–75: 0.11 % Predicted PEFR: 0.31 |
NEK1 | Positive |
| Subject 19 | M | White | Thoracolumbar scoliosis, developmental delay, autism | Sotos syndrome (OMIM #117550) | – | NSD1 | Positive |
| Subject 10 | M | Other | Abnormal thoracic cavity, lung hypoplasia, pancreatic insufficiency, failure to thrive, speech delay | Shwachman-Diamond syndrome (OMIM #260400) | – | SBDS | Positive |
| Subject 26 | M | White | Hemivertebrae, scoliosis, ambiguous genitalia, lobar holoprosencephaly, global developmental delay, micropenis, imperforate anus, seizures | Intellectual development disorder X-linked 99 (OMIM #300919) | – | USP9X | Strong candidate |
| Subject 9 | F | White | Short ribs, micromelia, brachydactyly, hemolytic uremic syndrome, kidney failure, kidney transplant, vision loss | Short-rib thoracic dysplasia 5 with or without polydactyly (OMIM #614376) |
% Predicted FVC: 0.97 % Predicted FEV1: 0.67 % Predicted FEV1/FVC: 0.83 % Predicted FEF25–75: 0.24 % Predicted PEFR: 0.71 % Predicted TLC: 0.71 % Predicted VC: 0.77 % Predicted RV: 0.15 |
WDR19 | Strong candidate |
| Subject 7 | M | Black Hispanic | Short ribs, failure to thrive, global developmental delay | Short-rib thoracic dysplasia 11 with or without polydactyly (OMIM #613363) | – | WDR34 | Positive |
| Subject 41 | F | Asian | Short ribs, thoracolumbar kyphosis | Short-rib thoracic dysplasia 11 with or without polydactyly (OMIM #613363) |
% Predicted FVC: 0.36 % Predicted FEV1: 0.32 % Predicted FEF25–75: 0.2 % Predicted TLC: 0.68 % Predicted FRC: 0.68 % Predicted RV: 0.52 % Predicted RV/TLC: 135 |
WDR34 | Positive |
FEF forced expiratory flow, FEV1 forced expiratory volume, FRC functional residual capacity, FVC forced vital capacity, PEFR peak expiratory flow rate, RV residual volume, TLC total lung capacity, VC vital capacity.