Table 2.
Molecular and clinical summaries of subjects carrying putatively damaging compound and double heterozygous changes in FREM2 and FRAS1 inherited from different parents
| Subject | Subject 1 | Subject 2 (DECIPHER 259497) | Subject 3 | Subject 4 | Subject 5 |
|---|---|---|---|---|---|
| Maternal allelea | FREM2 c.4031G>A, p.Arg1344His | FREM2 c.5938_5940delCTT, p.Leu1980del | FRAS1 c.2389G>A, p.Glu797Lys | FRAS1 c.9806G>A, p.Arg3269Gln | FREM2 c.4994C>T, p.Ser1665Phe |
| Paternal allelea | FREM2 c.4558C>T, p.Arg1520Trp | FREM2 c.5938_5940delCTT, p.Leu1980del | FREM2 c.4031G>A, p.Arg1344His | FREM2 c.4031G>A, p.Arg1344His | FRAS1 c.6323A>T, p.Asp2108Val |
| Other putatively-damaging alleles in CDH-related genesa | None | None reported | GLI3 c.2726C>G, p.Ala909Gly (maternal) | None | ROBO4 c.569G>C, p.Gly190Ala (maternal) |
| Age, sex and ethnicity | 6-month-old male, European descent | 3-year-old female | 6-month-old female, European descent | 8-year–9-month-old male, European descent | 7-year–2-month-old male, Filipino descent |
| Family history of CDH | None | None reported | None | None | Sister died of CDH |
| Diaphragm defect | Large, left-sided CDH | CDH | Right-sided diaphragmatic eventration, left-sided Bochdalek-type sac hernia | Left-sided sac hernia | Large, left-sided posterolateral CDH |
| Non CDH-related defects | Bilateral hydronephrosis | Global developmental delay, microcephaly, malformation of the heart and great vessels, PDA | Small umbilical hernia. congenital scoliosisb, bilateral hip dislocationb and joint contracturesb | Muscular VSD, PDA, mild pectus excavatum, bilateral hydronephrosis, cryptorchidism, inguinal hernia |
a
FREM2, NM_207361.5; FRAS1, NM_025074.6; GLI3, NM_000168.5; ROBO4, NM_019055.5; RYR1, NM_000540.
b
Likely secondary to central core disease caused by a de novo, known pathogenic RYR1 c.14581C>T, p.Arg4861Cys varianta (48).
PDA, patent ductus arteriosus; VSD, ventricular septal defect.