Table 1 Diagnoses from genomic autopsy. All ACMG-classified likely pathogenic (LP) and pathogenic (P) variants identified in the cohort, including follow-up investigations to confirm causality of eight VUS and two GUS. AR, autosomal recessive; AD, autosomal dominant; XLR, X-linked recessive; hom, homozygous; ch, compound heterozygous; dn, de novo; mat, maternal; pat, paternal; (2), two variants with the same inheritance model
From: Genomic autopsy to identify underlying causes of pregnancy loss and perinatal death
PED ID | Proband, major organ system | Inheritance | Gene symbol, amino acid or cDNA change(s) (ACMG classification) and follow-up to reclassify VUS |
|---|---|---|---|
001 | Skeletal | AR-hom | FGFR2 p.R255Q (LP) in vitro |
002 | Urogenital | AR-hom | DNAJB11 c.853-10 G > A (LP) RNA |
005 | Neurological, urogenital | AR-ch | MKS1 c.1024 + 1 G > T (P)/c.1408-34_6del29 (P) RNA |
007 | Lymphatic | AR-ch | MDFIC p.M131fs* (P)/p.F244L (LP) RNA, in vitro, in vivo, kindreds |
008 | Metabolic, endocrine | AD-pat | ABCC8 p.L1543P (P) |
012 | Skeletal | AR-ch | B3GAT3 p.R169W (P)/p.R225*(P) in vitro |
013 | Neurological | AR-ch | PIBF1 c.954 G > A (LP)/p.K353fs* (P) RNA |
014 | Lymphatic, skeletal | AD-dn | RIT1 p.A57G (P) |
017 | Hematopoietic, immune | AR-ch | TPI1 p.E105D (P)/c.544-1 G > C (P) RNA |
018 | Neurological | AD-dn | ARID1B p.W1499* (P) |
023 | Neurological | AR-ch | NDE1 p.T243Pfs* (P)/p.L245Pfs* (P) |
024 | Neurological | AR-ch | EIF2B2 c.284 + 5 G > T (P)/p.R172* (P) RNA |
031 | (Neuro-)Muscular | AR-ch | NEB p.M4377Kfs* (P)/p.H6907Ifs* (P) |
033 | (Neuro-)Muscular | AD-dn | NALCN p.L1324F (LP) |
042 | Skeletal | AR-hom | CANT1 p.E215K (LP) in vitro |
043 | Urogenital | AD-pat10–20% | PBX1 p.R107W (LP) |
044 | Cardiovascular | AD-dn | GNB2 p.K89E (P) kindreds |
046 | Cardiovascular | AD-dn (2) | KMT2D p.L2331* (P); SOS2 p.T295A (LP) |
053 | Urogenital | AD-dn | HNF1B c.344 + 2_5delTAGG (P) |
054 | Global | AD-dn | ARID1A p.A1136S (LP) |
056 | No abnormality detected | XLR | ARSL p.R403* (LP) |
057 | Skeletal | AD-dn | NIPBL p.Y2430C (P) |
063 | Metabolic, endocrine | AD-dn | SAMD9 p.R824Q (P) |
069 | Skeletal | XLR-dn | HUWE1 p.L2176R (LP) |
074 | Global | AD-dn | SMARCB1 p.R377H (P) |
084 | Neurological | AD-pat2–3% | TUBA1A p.R64W (P) |
085 | Global | AD-dn | RAF1 p.L613V (P) |
086 | Urogenital | AD-dn | GREB1L p.T1872Nfs* (P) |
091 | Respiratory | AD-dn | MAP2K2 p.E207A (LP) |
093 | Hematopoietic, immune | AD-dn | PTPN11 p.T73I (P) |
098 | Global | AR-ch | POLG p.R309H (P)/p.A467T (P) |
103 | Neurological | AD-dn | DDX3X p.P568L (P) |
104 | Hematopoietic, immune | AD-mat (2) | MECOM c.2208 + 4 A > T (LP) RNA; RYR2 p.V4176M (LP) |
116 | Skeletal, cardiovascular | AR-ch | ADAMTSL2 p.R113H (P)/p.G354Afs* (P) |
119 | Skeletal, lymphatic | AD-dn | LZTR1 p.G301V (LP) |
121 | Pulmonary, cardiovascular | AD-mat | FOXF1 p.G302Pfs* (P) |
138 | Urogenital | AR-hom | PKHD1 p.R564* (P) |
156 | (Neuro-)Muscular | AD-dn | ACTA1 p.E272K (LP) |
157 | Neurological | AD-dn | USP9X p.F208Cfs* (P) |
158 | Neurological | AD-dn | ACTA1 p.G199D (LP) |
165 | Urogenital | AD-dn | USP9X p.Q2246* (P) |
169 | Neurological | AR-hom | TRAPPC12 p.Q149* (P) |
176 | Urogenital | AD-dn | GATA3 p.C285Y (LP) |
178 | Urogenital | AD-dn | ARCN1 p.R170* (P) |
187 | Neurological | AD-dn | TUBA1A p.R79C[P] |
189 | Skeletal | AD-dn | NIPBL p.D1991N (LP) |
199 | Cardiovascular | AD-dn | PRKACB p.H135L (LP) |
200 | Neurological | XLR | ARSL p.E407* (LP) |
207 | Global | AD-dn | KMT2D p.Q2014* (P) |
226 | Cardiovascular | AD-dn | FGFR2 p.P253R (P) |
231 | Neurological | AR-ch | OSGEP p.R186* (LP)/p.R247Q (P) |
233 | Other | AD-mat | COL2A1 p.C1289Pfs* (LP) |
