Table 1.
Individuals with CDH+ for whom a definitive, probable or provisional diagnosis was made by exome sequencing.
| Gene† | Variant(s) | Inheritance | Variant Type |
Diagnosis |
|---|---|---|---|---|
| Definitive 19/76 = 25% | ||||
| ABL1*[19] | c.1066G>A, p.(A356T) | De Novo | Pathogenic | Congenital heart defects and skeletal malformations syndrome (MIM #617602) |
| ABL1*[19] | c.734A>G, p.(Y245C) | De Novo | Pathogenic | ” |
| ADAT3*[20] | c.[586_587delinsTT];[587C>T], p.[(A196L)];[(A196V)] | Inherited in Trans | VUS, VUS | Mental retardation, autosomal recessive 36; (MIM #615286) |
| ALG12 | c.[165C>A];[437G>A], p.[(Y55*)];[(R146Q)] | Inherited in Trans | Pathogenic, Pathogenic | ALG12-CDG (MIM #607143) |
| ANKRD11 | c.1372C>T, p.(R458*) | Paternal | Pathogenic | KBG syndrome (MIM #148050) |
| BRCA2 | c.[4965C>G];[7007G>C], p.[(Y1655*)];[(R2336P)] | Inherited in Trans | Pathogenic, Pathogenic | Fanconi anemia, complementation group D1 (MIM #605724) |
|
FBN1*[21] TRPS1 |
c.4786C>T, p.(R1596*); c.1630C>T, p.(R544*) | De Novo De Novo |
Pathogenic Pathogenic |
Marfan syndrome (MIM #154700); Trichorhinophalangeal syndrome type I (MIM #190350) |
| FOXC2 § | c.563_573del, p.(P188fs) | De Novo | Pathogenic | Lymphedema-distichiasis syndrome (MIM #153400) |
| FOXP1 | c.1718_1722+8del, p.? | De Novo | Pathogenic | Mental retardation with language impairment and with or without autistic features (MIM #613670) |
| KMT2D | c.10258dupA, p.(I3420fs) | De Novo | Pathogenic | Kabuki syndrome 1 (MIM #147920) |
| KMT2D | c.13543dupA, p.(R4515fs) | De Novo | Pathogenic | “ |
| KMT2D | c.7613dupT, p.(Q2540Sfs) | De Novo | Pathogenic | ” |
| MCPH1 | c.[586delC];[586delC], p.[(Q196fs)];[(Q196fs)] | Inherited in Trans | Pathogenic, Pathogenic | Microcephaly 1, primary, autosomal recessive (MIM #251200) |
| MYRF*[8] | c.3239dupA, p.(E1081Gfs) | De Novo | Likely Pathogenic | Cardiac-urogenital syndrome (MIM #618280) |
| MYRF*[8] | c.350_366delinsT, p.(G117Vfs) | Not Maternal | Likely Pathogenic | ” |
| PDHA1 | c.1035_1036dupGA, p.(I346Rfs) (Het in female) | Not Maternal | Pathogenic | Pyruvate dehydrogenase E1-alpha deficiency (MIM #312170) |
| RASA1 | c.1103-1G>T, p.? | Paternal | Pathogenic | Capillary malformation-arteriovenous malformation 1(MIM #608354); Partially solved |
| SMARCA4 | c.2936G>A, p.(R979Q) | De Novo | Pathogenic | Coffin-Siris syndrome 4 (MIM #614609) |
| ZFPM2 | c.757_761dup, p.(C255fs) | ? | Pathogenic | Diaphragmatic hernia 3 (MIM #610187) |
| Probable 9/76 = 12% | ||||
| ABL1 | c.352T>C, p.(W118R) | De Novo | Likely Pathogenic | Congenital heart defects and skeletal malformations syndrome (MIM #617602) |
| ALG12 | c.[437G>A];[930_931delAC], p.[(R146Q)];[(R311fs)] | Inherited in Trans | Pathogenic, Likely Pathogenic | ALG12-congenital disorder of glycosylation (MIM #607143) |
| DDX3X | c.1304T>C, p.(L435P) (Sex not indicated); | De Novo | Likely Pathognic | Intellectual developmental disorder, X-linked, syndrome, Snijders Blok type (MIM #300958) |
| EP300 | c.2660C>T Mosaic 12%, p.(T887I) Mosaic | De Novo | Likely Pathogenic | Rubinstein-Taybi syndrome 2 (MIM #613684) |
| HCCS | c.308_309insAGT, p.(V103dup) (Sex not indicated) | De Novo | Likely Pathogenic | Linear skin defects with multiple congenital anomalies 1 (MIM #309801) |
| KMT2D | c.1967delT, p.(L656fs) | ? | Likely Pathogenic | Kabuki syndrome 1 (MIM #147920) |
| POGZ | c.2849dupC, p.(V951Sfs) | ? | Likely Pathogenic | White-Sutton syndrome (MIM #616364) |
| TCF12 | c.1808G>A, p.(R603Q) | De Novo | Likely Pathogenic | Craniosynostosis 3 (MIM #615314) |
| TRAF7 | c.1886G>A, p.(S629N) | De Novo | Likely Pathogenic | Cardiac, facial, and digital anomalies with developmental delay (MIM #618164) |
| Provisional 7/76 = 9% | ||||
|
B3GALT6
IDS |
c.[929A>G];[795A>C], p.[(Y310C)];[(E265D)] c.1144G>C, p.(D382H) (Hemi in male) |
Inherited in Trans Maternal |
VUS, VUS VUS |
Ehlers-Danlos syndrome, spondylodysplastic type, 2 (MIM #615349) Mucopolysaccharidosis II (MIM #309900) |
|
EP300
DKC1 SOS1 |
c.3592T>C, p.(Y1198H) c.−142C>G, p.? (Het in female) c.3298G>T, p.(D1100Y) |
? ? ? |
VUS Pathogenic VUS |
Rubinstein-Taybi syndrome 2 (MIM #613684) Dyskeratosis congenita, X-linked (MIM #305000) Noonan syndrome 4 (MIM #610733) |
| FANCI | c.2422A>T, p.(K808*) | Maternal | Pathogenic | Fanconi anemia, complementation group I (MIM #609053) |
| LRP2 | c.[3667+1G>A];[5390A>G], p.[?];[(N1797S)] | Inherited in Trans | Likely Pathogenic, VUS | Donnai-Barrow syndrome (MIM #222448) |
| MED12 | c.5691_5692delGT, p.(Y1898fs) (Het in female) | De Novo | Pathogenic | MED12-related disorder (MIM #300895, #305450, #309520) |
| SLC2A10 | c.[67G>A];[67G>A], p.[(G23S)];[(G23S)] | ? | VUS, VUS | Arterial tortuosity syndrome (MIM #208050); Partially solved |
|
SMARCC2
LMX1B |
c.1651-2A>G, p.? c.904C>T, p.(Q302*) |
Not Maternal Not Maternal |
VUS VUS |
Coffin-Siris syndrome 8 (MIM #618362) Nail-patella syndrome (MIM #161200) |
†
Genes clearly associated with an increased risk of developing CDH are shown in bold.
‡
Originally reported as VUS/VUS prior to publication.
*
Subject was previously published.
§
Molecular diagnosis made by exome sequencing on identical twin. “ = same as above. ? = unknown. LP = Likely Pathogenic, P = Pathogenic, VUS = variant of unknown significance.