TABLE 1.
Pathogenic/likely pathogenic variants with the reported phenotype
| Phenotype | Indications | Gene | Variants | Classification | Serial no. | |
|---|---|---|---|---|---|---|
| 1 | Hx of second‐ and third‐degree relative died with GDD, hypotonia, and cardiac condition. | ND | POLR3A | c.1909 + 22G > A | Pathogenic | 1 |
| 2 | Parent of two children deceased with lactic acidosis and severe hypotonia. | ND | ECHS1 | c.88þ5G | Pathogenic | 2 |
| NEB | c.17358T > A:p.N5786K | Likely pathogenic | 3 | |||
| 3 | VSD, kidney malformation abnormal limb posture, cerebellar hypoplasia, hypertelorism and severe IUGR. | IUFD | CTU2 | c.1086 + 5G > A | Pathogenic | 4 |
| 4 | Persistent lactic acidosis, hypertrophic cardiomyopathy, high‐liver enzyme level. | ND | ACAD9 | c.1240C > T (p.Arg414Cys) | Pathogenic | 5 |
| CYP21A2 | c.92C > T | Pathogenic | 6 | |||
| 5 | Fetal hydrops fetalis, pleural effusion, pericardial effusion, ascites ended by fetal demise. | ND | GUSB | c.1429C > T (p.Arg477Trp) | Pathogenic | 7 |
| 6 | Second‐ or third‐degree nephews/nieces who died early in life (2nd or 3rd day of life). | ND | MMUT | c.329A > G (p.Tyr110Cys) | Pathogenic | 8 |
| 7 | Recurrent neonatal deaths. | ND | IBA57 | c.316A > G (p.Thr106Ala) | Pathogenic | 9 |
| 8 | Recurrent neonatal deaths. | ND | BCS1L | c.385G > A (p.Gly129Arg) | Pathogenic | 10 |
| 9 | Recurrent neonatal deaths | ND | STXBP2 | c.1485 + 1G > A | Pathogenic | 11 |
| 10 | Recurrent neonatal deaths. | ND | HSPG2 | c.790C > T (p.Arg264*) | Likely pathogenic | 12 |
| 11 | Recurrent neonatal deaths. | ND | CANT1 | c.902_906dup (p.Ser303Alafs*21 | Pathogenic | 13 |
| 12 | Recurrent neonatal deaths. | ND | MMAB | c.197‐1G > T | Pathogenic | 14 |
| 13 | Recurrent neonatal deaths. | ND | MALT1 | c.1240G > A (p.Gly414Arg) | Likely pathogenic | 15 |
| 14 | Dysmorphic, short neck, narrow restricted chest, faint heart sound, short four limbs with polydactyly of the upper limb. | ND | EVC2 | c.2017_2021del (p.Thr673Glufs*14) | Likely pathogenic | 16 |
| 15 | Early neonatal death with bilateral renal agenesis. | ND | FRAS1 | c.1226dup (p.Gln411Thrfs*26) | Likely pathogenic | 17 |
| 16 | Early death, microcephaly, Potter‐like facies, sloping head, microphthalmia, low‐set ears, short webbed neck, occipital encephalocele, polycystic kidneys, ambiguous genitalia, polydactyly (suspected diagnosis ‐ Meckel‐Gruber syndrome). | ND | CEP290 | c.613C > T (p.Arg205*) | Pathogenic | 18 |
| 17 | Microcephaly, Potter‐like facies, sloping head, microphthalmia, low‐set ears, hypertelorism, occipital encephalocele, polycystic kidneys, oligohydramnios, talipes, polydactyly. | ND | TCTN2 | c.1506‐2A > G | Pathogenic | 19 |
| 18 | Recurrent neonatal death due to polycystic kidney disease. | ND | NPHS1 | c.2540_2543delCTAA (p.Thr847ArgfsTer57) | Likely pathogenic | 20 |
| 19 | Severe hydrocephalus, encephalocele and lissencephaly in two pregnancies; mother is healthy apart from hypothyroidism with no other medical issues. | ND | ISPD | c.1186G > T (p.Glu396*) | Pathogenic | 21 |
| 20 | Characteristic facies, hypoplastic terminal phalanges, osteopenia, albinoid fundus, markedly impaired retinal function, recurrent infections, persistent anemia with anisopoikilocytosis. | ND | CRIPT | c.141delT (p.Phe47Leufs*84) | Pathogenic | 22 |
| 21 | Anencephaly, polydactyly, cystic kidney (suspected diagnosis Meckel syndrome). | ND | PEX26 | c.228C > T (p.Gly76Alafs*5) | Pathogenic | 23 |
| 22 | Microcephaly, agenesis of corpus callosum, occipital encephalocele, multicystic kidney, hypotonia, IUFR (suspected Meckel syndrome). | ND | MKS1 | c.261 + 2T > A | Pathogenic | 24 |
| 23 | Meckel syndrome‐affected fetuses. | IUFD | CC2D2A | c.3084delG (p.Lys1029Argfs*3) | Pathogenic | 25 |
| 24 | Four neonatal deaths with congenital hydrocephalus. | ND | CC2D2A | c.3084delG (p.Lys1029Argfs*3) | Pathogenic | 26 |
| 25 | Bilateral genu recurvatum, narrow chest with mild to moderate inspiratory stridor, no organomegaly, generalized hypotonia, hyporeflexia, mild microcephaly, respiratory distress. | ND | PEX26 | c.228C > T (p.Gly76Alafs*5) | Pathogenic | 27 |
| 26 | Hypotonia, dysmorphic feature, low‐set ears, micrognathia, high‐arched palate, bilateral talipes, equinovarus, poor feeding. | ND | EML1 | c.2233G > A (p.Val745Ile) | Pathogenic | 28 |
| 27 | Recurrent miscarriage. | RPL | LGI4 | c.834del (p.Ser279Alafs*191) | Likely pathogenic | 29 |
| 28 | Recurrent spontaneous abortion. Abnormal facial shape; CHD, atrial septal defect; CNS abnormality; cerebellar hypoplasia; congenital onset; depressed nasal bridge; dilation of lateral ventricles; enlarged cisterna magna; hernia of the abdominal wall; high, narrow palate; hypertonia; low‐set ears; microcephaly; optic atrophy; optic disc hypoplasia; overlapping fingers; ventriculomegaly. | RPL+ IUFD | KLHL7 | c.807C > A | Likely pathogenic | 30 |
| 29 |
Abnormal vertebral morphology, renal abnormality, aplasia/hypoplasia of the cerebellar vermis, clinodactyly, hydrocephalus, low‐set ears, micrognathia, multiple renal cysts, oligohydramnios, polydactyly, rocker bottom foot and ventriculomegaly. Asymptomatic parents are consanguineous, and they lost two children at the ages 33 and 32 G.W. |
IUFD | TMEM231 | c. 930‐5_930‐2delinsTGTC | Likely pathogenic | 31 |
| 30 | Recurrent pregnancy loss. | RPL | CHRNG | c.1019C > T | Likely pathogenic | 32 |
| GAA | c.1430delT | Likely pathogenic | 33 | |||
| 31 | One child died with unilateral renal agenesis, recurrent spontaneous abortion. Hx of previous hydatidiform mole. | RPL | DNAH5 | c.5503C > T(p.Gln1835Ter) | Likely pathogenic | 34 |
| AMHR2 | c.994C > T | Pathogenic | 35 | |||
| PTPRQ | c.4155 + 1G > A | Pathogenic | 36 | |||
| PCDH15 | c.4604_4608dup | Pathogenic | 37 | |||
| 32 | Recurrent miscarriages and IUFD 3X skeletal phenotype in the aborted fetus. | RPL | TRIP11 | c.3082C > T (p.Arg1028*) | Pathogenic | 38 |
| 33 | Multiple malformations. | IUFD | CDT1 | c.1393dupT (p.V464fs) | Likely pathogenic | 39 |
| 34 | Recurrent neonatal deaths with renal phenotype. | ND | LAMB2 | c.4276dupG (p.Ala1426Glyfs*6) | Likely pathogenic | 40 |
| 35 | Second‐ or third‐degree cousin died with phenotype consistent with liver disease, and hypoglycemia | ND | MRAP | c.105_106 + DEL P.(His36Phefs*84) | Pathogenic | 41 |
| 36 | Recurrent failed implantation after IVF and 2 miscarriages, one died with recurrent infection | RPL | SLC26A3 | c.79G > C p.(Gly27Arg) | Pathogenic | 42 |
| AK2 | c.559G > T p.(Gly187*) | Likely pathogenic | 43 | |||
| 37 | Abnormal stomach, congenital arthrogryposis multiplex, talipes equinovarus. | ND | LGI4 | c.639G > A P.(Trp213*) | Likely pathogenic | 44 |
| 38 | Son 1: Intracranial cystic lesion, Neonatal death, Premature birth; Son 2: Abnormal heart morphology, Abnormality of the kidney, Neonatal death, Premature birth. | ND | NPHP3 | c.2694‐2_2694‐1del | Pathogenic | 45 |
| 39 | Two previous IUFD at 24 weeks and 27 weeks with scan showing skeletal changes | ND | TRIP11 | c.763C > T p.R255X | Pathogenic | 46 |
| 40 |
Two offspring passed away with 1‐ Coarctation of aorta; Hydrocephalus and brain anomalies 2‐ Atrial septal defect, Hydrocephalus; Severe, other anomalies + recurrent pregnancy loss. |
ND IUFD |
MPDZ | c.628C > T. p.(Gln210*) | Pathogenic | 47 |
| 41 | Hx of cousins with early death with cardiomyopathy. | ND | LZTR1 | c.639del P.(Cys214Alafs*38) | Likely pathogenic | 48 |
| 42 | Recurrent neonatal deaths. | ND | KIAA0586 | c.78dup (p.Lys27fs*) | Likely pathogenic | 49 |
| 43 | Neonatal death at 3 DOL with positive NBS VLCAD | ND | ACADVL | c.65C > A;p.Ser22X | Pathogenic | 50 |
Abbreviations: RPL: recurrent pregnancy loss including miscarriage and IUFD; ND: neonatal death; PCS: preconception screening in the presence of cousins with genetic condition.