Family ID | Consanguinity | Phenotype in the deceased child and DD | Number/gender/age of lost child/miscarriage | Gene (OMIM) | Variant identified in the couples | Variant confirmed in deceased child | CADD/Classification of variant | Disease (OMIM) Increased risk for autosomal recessive disorder | spontaneous pregnancy with prenatal diagnosis | PGD |
---|---|---|---|---|---|---|---|---|---|---|
1 | yes | intrauterine epilepsy, severe brain malformation DD: early epileptic encephalopathy | 3 m + f neonatal | CTSD (*116840) FTCD (*606806) | NM_001909: c.268_269insC p.(Gln90Profs*50) mat and pat het NM_001320412: c.530G > A p.(Gly177Glu) mat and pat het | CTSD: hom | CADD: n.a./Class 4 CADD: 25.8/Class 4 | Ceroid lipofuscinosis, type 10 (#610127) Glutamate formiminotransferase deficiency (#229100) | two, CVS: CTSD: het FTCD: wt and het | planned |
2 | no | severe congenital lactic acidosis DD: pyruvate dehydrogenase deficiency | 1 f neonatal | COQ2 (*609825) | mother: NM_015697: c.1197delT p.(Asn401Ilefs*15) father: c.764C > T p.(P255L) | no | CADD: 23.7/Class 5 CADD: 29/ Class 4 | Coenzyme Q10 deficiency, primary, type 1 (#607426) | yes, AC: COQ2: comp het | in progress |
3 | yes | SIDS, severe hypertrophic cardiomyopathy DD: FAOD, primary carnitine deficiency | 1 m 5 months 1 MC | ACADVL (*609575) | NM_001033859: c.1274 T > C, p.(L425P) mat and pat het | ACADVL : hom | CADD: 27.4/Class 4 | VLCAD deficiency, (#201475) | no | planned |
4 | yes | hyperinflammatory syndrome with hepatosplenomegaly, suspicion of hemophagocytic lymphohistiocytosis DD: PID | 1f neonatal 3 MC | UNC13D (*608897) | NM_199242: c.2447 + 1G, p.? donor site change) mat and pat het | no | CADD: 27.4/Class 4 | Familial hemophagocytic lymphohistiocytosis type 3 (#608898) | no | planned |
5 | yes | spasticity, muscular hypotonia, epileptic encephalopathy, optic atrophy DD: Leigh syndrome, Pelizeus-Merzbacher syndrome | 1 m 11 months | BRAT1 (*614506) | NM_152743: c. 1280G > A p.(Arg427Gln) mat and pat het | no | CADD: 32/ Class 4 | Rigidity and multifocal seizure syndrome (#614498) | prenatal diagnostics declined | planned |
6 | no | severe muscular hypotonia, respiratory insufficiency, seizures DD: mitochondriopathy | 1 f 16Â months 1 MC | Â | none | Â | Â | Â | yes: no prenatal diagnostics, healthy child | no |
7 | yes | severe lissencephaly type 2 | 1 f, 2Â m neonatal | PALLD (*608092) | NM_001166108: Exon 1 deletion mat and pat het | PALLD : hom | CADD: n.a./ Class 3 | No OMIM disease entry mouse: migration defect [17] | no | planned |
8 | yes | dilated cardiomyopathy, congenital myopathy DD: mitochondriopathy | 1 f 5Â months 1 MC | none | none | no | Â | Â | yes: no prenatal diagnostics: healthy child | no |
9 | no | 1: meningocele, hydrocephalus 2: intracerebral hemorrhage, respiratory insufficiency DD: exogenous factors | 1Â m neonatal 1 f neonatal 1 MC | none | none | no | Â | Â | no | no |
10 | yes | 3 miscarriages with ascites, cardiomegaly, skeletal deformity, biochemical suspicion of mucolipidosis type II | 4 MC (f + m) | none | none | no |  |  | no | no |
11 | no | early-onset severe epilepsy DD: infantile epileptic encephalopathies | 1 f, 2 m 16–21 months | none | none | no |  |  | no | no |
12 | yes | microcephaly, IUGR, cerebellar hypoplasia, rockerbottom feet, hydronephrosis | 1 f 6Â months 3 MC | none | none | no | Â | Â | no | no |
13 | no | anencephaly, iu lethal DD: folate deficiency | 2 MC 11th week of gestation | APAF1 (*602233) | mother: NM_181861: c.1350C > G p.(Cys450Trp) father: c.3127C > G p.(His1043Asp) | APAF1 : comp het | CADD: 23.1/Class 3 CADD: 25.7/ Class 3 | No OMIM disease entry mouse model: anencephaly, neurogenesis defect [20] | no | planned |