| Literature DB >> 35179721 |
Salwa Al Ubaidani1, Khalsa Al Kharusi2, Zandré Bruwer3, Fathiya Al Murshedi2, Almundher Al-Maawali2, Abeer Al Sayegh2, Adila Al Kindy2, Nihal Al Riyami4, Tamima Al Dughaishi4, Mouza Al Salmani1, Nadia Al Hashmi5, Maryam Al Shehhi5, Badriya Al Fahdi1, Sumaya Al Amri1, Khalid Al-Thihli2.
Abstract
Studies on the acceptance of prenatal diagnosis and termination of pregnancy for single gene disorders within Islamic societies in the Middle East are limited. A few have examined the attitudes toward pregnancy termination for fetal indications, but a dearth of published data exists on actual behavior and uptake. This study reports on all prenatal diagnosis requests for single gene disorders, from the Sultanate of Oman, over 9 years. A retrospective study was conducted during which the medical records of all women who performed prenatal diagnoses for single gene disorders were reviewed. A total of 148 invasive procedures were performed for 114 families. The total number of yearly requests for prenatal diagnosis increased exponentially from three in 2012 to 21 in 2020. Sixty-four different diagnoses were tested for with the majority being autosomal recessive in nature. Seventy-one percent (28/39) of cases where an affected pregnancy was identified were terminated. Fifty-two of the 114 women (45.6%) repeated prenatal diagnosis in a future pregnancy. Seventy-two couples (63%) were consanguineous parents related as second cousins or closer. The majority of tests performed were for couples from Muscat (27%), Albatinah (27%), and Alsharqiya (20.3%) governorates in Oman. The findings of this study provide evidence that prenatal diagnosis is an acceptable reproductive option to prevent the occurrence of genetic disorders that meet termination eligibility criteria as outlined by the Islamic Jurisprudence (Fiqh) Council Fatwa, among Omani Muslim couples.Entities:
Keywords: Genetic disorders; Muslim; Oman; Prenatal genetic diagnosis; Termination of pregnancy
Year: 2022 PMID: 35179721 PMCID: PMC8854480 DOI: 10.1007/s12687-022-00584-1
Source DB: PubMed Journal: J Community Genet ISSN: 1868-310X
Criteria to guide termination of pregnancy-related decisions for genetic disorders in Oman
| Guidelines defining eligibility for termination of pregnancy of genetic disorders* | |
|---|---|
| Criteria pertaining to the condition | Criteria pertaining to diagnostic confirmation |
1. The condition results in severe and debilitating congenital malformations or developmental outcomes or severe organ system dysfunction 2. The condition is congenital or of infantile onset 3. The natural history of the condition is established. For ultra-rare conditions with poorly established natural history, the condition should have consistently followed the same clinical course among affected relatives in the same families or in families known to the genetic clinic 4. The condition does not show significant variability in severity of the phenotype or in penetrance in a way that impedes reliable prediction of the outcomes | 5. The condition is genetically confirmed2 (molecular confirmation or chromosomal where appropriate) 6. Only pathogenic (P) or likely pathogenic (LP) variants (Harrison et al 7. Variants reported in clinical laboratories to be of uncertain significance maybe entertained |
1Families with conditions that have ongoing phase III/IV therapeutic trials may only be considered for termination if they are of congenital, infantile, or of early childhood onset
2Certain conditions may be exempt from molecular confirmation. Examples would include conditions where the phenotype is well known to be lethal and obvious during prenatal diagnostic imagining such as anencephaly, pentalogy of Cantrell, and lethal skeletal dysplasias like achondrogenesis
*Both condition and diagnostic criteria should be met before termination of pregnancy can be offered as an option
Fig. 1Number of prenatal genetic diagnostic tests performed for single gene disorders between 2012 and 2020 (n = 148). Data includes repeat tests performed due to analysis failure. Repeat testing included one case in 2013, 2016, 2017, and 2020 and two cases in 2018
Number of invasive procedures performed in successive pregnancies within the cohort
| Number of PND’s undertaken | Number per category | Percentage |
|---|---|---|
| Single request for PND | 90 | 60.80% |
| Repeated PND twice | 42 | 28.40% |
| Repeated PND three times | 6 | 4.05% |
| Repeated PND four times | 4 | 2.70% |
| Repeated PND due to analysis failure | 6 | 4.05% |
| Total | 148 | 100% |
PND, prenatal genetic diagnosis
Genetic disease in cohort of patients undertaking prenatal genetic diagnosis (PND)
| Gene | Condition (OMIM) | Inheritance | Number of tests performed for each conditiona | |
|---|---|---|---|---|
| 1 | AARS2 | Combined oxidative phosphorylation deficiency 8 | AR | 1 |
| 2 | AGXT | Primary hyperoxaluria | AR | 2 |
| 3 | ALDH3A2 | Sjogren-Larsson syndrome | AR | 1 |
| 4 | ALG12 | Congenital disorder of glycosylation, type Ig | AR | 1 |
| 5 | AMPD2 | Pontocerebellar hypoplasia, type 9 | AR | 1 |
| 6 | ANTXR2 | Hyaline fibromatosis syndrome | AR | 2 |
| 7 | AP3B2 | Developmental and epileptic encephalopathy 48 | AR | 1 |
| 8 | AP3D1 | Hermansky-Pudlak syndrome 10 | AR | 1 |
| 9 | ARSA | Metachromatic leukodystrophy | AR | 3 |
| 10 | ASL | Argininosuccinic aciduria | AR | 1 |
| 11 | ASPA | Canavan disease | AR | 1 |
| 12 | ATP8A2 | Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 | AR | 1 |
| 13 | B3GALNT2 | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 11) | AR | 1 |
| 14 | CPS1 | Carbamoylphosphate synthetase I deficiency | AR | 2 |
| 15 | CTSA | Galactosialidosis | AR | 3 |
| 16 | DGUOK | Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) | AR | 2 |
| 17 | DLAT | Pyruvate dehydrogenase E2 deficiency | AR | 1 |
| 18 | DMD | Duchenne muscular dystrophy | XL | 1 |
| 19 | EIF2AK3 | Wolcott-Rallison syndrome | AR | 1 |
| 20 | EMC1 | Cerebellar atrophy, visual impairment, and psychomotor retardation | AR | 1 |
| 21 | ERCC5 | Xeroderma pigmentosum, group G/Cockayne syndrome | AR | 2 |
| 22 | ETFDH | Glutaric acidemia II | AR | 3 |
| 23 | FBXL4 | Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) | AR | 2 |
| 24 | FGFR3 | Thanatophoric dysplasia, type II | AD | 2 |
| 25 | FKTN | Muscular dystrophy-dystroglycanopathy (congenital without mental retardation) type 4B | AR | 1 |
| 26 | FRAS1 | Fraser syndrome | AR | 1 |
| 27 | GALC | Krabbe disease | AR | 1 |
| 28 | GAN | Giant axonal neuropathy | AR | 1 |
| 29 | GLB1 | GM1-gangliosidosis, type I | AR | 1 |
| 30 | HBB | Beta thalassemia | AR | 2 |
| 31 | HSD17B4 | Perrault syndrome 1 | AR | 1 |
| 32 | IBA57 | Multiple mitochondrial dysfunctions syndrome 3 | AR | 1 |
| 33 | IDUA | Mucopolysaccharidosis type I (Hurler) | AR | 1 |
| 34 | IFT172 | Short-rib thoracic dysplasia 10 with or without polydactyly | AR | 1 |
| 35 | ITGA8 | Renal hypoplasia/aplasia 1 | AR | 1 |
| 36 | LAMA3 | Epidermolysis bullosa, junctional, Herlitz type | AR | 1 |
| 37 | MPV17 | Mitochondrial DNA depletion syndrome type 6 | AR | 1 |
| 38 | NAGLU | Mucopolysaccharidosis type IIIB (Sanfilippo B) | AR | 1 |
| 39 | NFASC | Neurodevelopmental disorder with central and peripheral motor dysfunction | AR | 1 |
| 40 | OSTM1 | Osteopetrosis | AR | 2 |
| 41 | PC | Pyruvate carboxylase deficiency | AR | 1 |
| 42 | PCCB | Propionic acidemia | AR | 1 |
| 43 | PEX1 | Peroxisome biogenesis disorder 1A (Zellweger) | AR | 7 |
| 44 | PEX14 | Peroxisome biogenesis disorder 13A (Zellweger) | AR | 1 |
| 45 | PEX26 | Peroxisome biogenesis disorder 7A (Zellweger) | AR | 2 |
| 46 | PGAP3 | Hyperphosphatasia with mental retardation syndrome 4 | AR | 1 |
| 47 | PKHD1 | Polycystic kidney disease 4, with or without hepatic disease | AR | 1 |
| 48 | PLA2G6 | Neurodegeneration with brain iron accumulation 2B | AR | 1 |
| 49 | PRUNE1 | Prune-1 syndrome | AR | 3 |
| 50 | RAB3GAP1 | Warburg-Micro syndrome | AR | 2 |
| 51 | RARS | Hypomyelinating leukodystrophy type 9 | AR | 1 |
| 52 | RARS2 | Pontocerebellar hypoplasia, type 6 | AR | 1 |
| 53 | RECQL4 | RAPADILINO syndrome | AR | 1 |
| 54 | SMN1 | Spinal muscular atrophy-1 | AR | 17 |
| 55 | SPINK5 | Netherton syndrome | AR | 1 |
| 56 | STT3A | Congenital disorder of glycosylation, type Iw | AR | 2 |
| 57 | SUOX | Sulfite oxidase deficiency | AR | 3 |
| 58 | TBCE | Hypoparathyroidism-retardation-dysmorphism syndrome | AR | 3 |
| 59 | TINF2 | Dyskeratosis congenita | AD | 1 |
| 60 | TMEM138 | Joubert syndrome 16 | AR | 1 |
| 61 | TRIP11 | Achondrogenesis, type IA | AR | 1 |
| 62 | TRNT1 | Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay | AR | 1 |
| 63 | UGT1A1 | Crigler-Najjar syndrome, type I | AR | 1 |
| 64 | VPS33B | Arthrogryposis, renal dysfunction, and cholestasis 1 | AR | 5 |
aData includes repeat procedures. Individual TOP outcomes were not recorded to maintain the privacy of the families’ decisions. AR, autosomal recessive; AD, autosomal dominant; XL, X-linked
Fig. 2Geographic distribution of couples requesting prenatal genetic diagnosis (PND) in Oman. n = PND requests per governorates. P, population size as per 2010 Oman Census data (Governorates of Oman 2021). *Sultan Qaboos University Hospital and Royal Hospital are both located within the capital city of Muscat (Muscat governorate). Albatinah and Alsharqiya are made up of a North and South governorate. PND data for the entire region (North and South) are shown for these two governorates