UNASSIGNED: Premarital screening (PMS) is an essential global measure that seeks to reduce the occurrence of specific genetic disorders and sexually transmitted diseases common in consanguineous marriages. Due to the lack of a nationwide study, this research was designed to comprehend how unmarried individuals perceive the risks and benefits of PMS.
UNASSIGNED: A cross-sectional study was conducted using an online questionnaire distributed through different social media platforms, responses from the native adult population (18-49 years) Saudi Arabia was only included in the study. The questionnaire was based on the Health Belief Model (HBM) to assessing seven different constructs including susceptibility, seriousness, benefits-, barriers-, & cues- to action, self-efficacy, and social acceptance. Data frequency was represented by mean and standard deviation; chi-square and t-tests were conducted for the comparison of independent and dependent variables. A multinomial logistic regression was used to predict factors influencing decisions related to PMS.
UNASSIGNED: 1,522 participants completed the survey, mostly 18-25 years old and most of them were women. The majority were single with 85 men and 1,370 women. Most participants (59.6%) believed their parents were related, while 40.5% did not. 122 respondents reported they had to marry within their tribe. Findings revealed significant correlations among all HBM themes, with varying strengths. Notably, a moderate positive relationship was found between the perception of benefits and cues to action, suggesting that enhancing the perceived benefits of PMS could facilitate safe marriage practices. Multinomial regression analysis revealed that demographic factors and health beliefs significantly influence individuals\' intentions and behaviors toward PMS and safe marriage.
UNASSIGNED: The study concludes that by identifying and addressing barriers, and promoting positive social acceptance, PMS can significantly contribute to preventing genetic diseases and promoting safe marriage practices, although the cross-sectional design limits the establishment of causal relationships and further research is needed.

BACKGROUND: Autosomal recessive non-syndromic hearing loss (NSHL) and cone dystrophies (CODs) are highly genetically and phenotypically heterogeneous disorders. In this study, we applied the whole exome sequencing (WES) to find the cause of HL and COD in an Iranian consanguineous family with three affected individuals.
METHODS: Three members from an Iranian consanguineous family who were suffering from NSHL and visual impairment were ascertained in this study. Comprehensive clinical evaluations and genetic analysis followed by bioinformatic and co-segregation studies were performed to diagnose the cause of these phenotypes. Data were collected from 2020 to 2022.
RESULTS: All cases showed congenital bilateral NSHL, decreased visual acuity, poor color discrimination, photophobia and macular atrophy. Moreover, cornea, iris and anterior vitreous were within normal limit in both eyes, decreased foveal sensitivity, central scotoma and generalized depression of visual field were seen in three cases. WES results showed two variants, a novel null variant (p.Trp548Ter) in the PDE6C gene causing COD type 4 (Achromatopsia) and a previously reported variant (p.Ile84Thr) in the PDZD7 gene causing NSHL. Both variants were found in the cis configuration on chromosome 10 with a genetic distance of about 8.3 cM, leading to their co-inheritance. However, two diseases could appear independently in subsequent generations due to crossover during meiosis.
CONCLUSIONS: Here, we could successfully determine the etiology of a seemingly complex phenotype in two adjacent genes. We identified a novel variant in the PDE6C gene, related to achromatopsia. Interestingly, this variant could cooperatively cause visual disorders: cone dystrophy and cone-rod dystrophy.

BACKGROUND This retrospective study aimed to evaluate the presentation, diagnosis, management, and outcomes of 27 patients diagnosed with osteogenesis imperfecta at a single center in Türkiye between January 2011 and January 2020. MATERIAL AND METHODS We analyzed data from the medical records of 27 patients with osteogenesis imperfecta admitted to Çukurova University Faculty of Medicine, Department of Orthopedics and Traumatology, between January 2011 and January 2020. The data included the clinical examination notes of the cases classified according to the Sillence and Shapiro systems, age, sex, parental consanguinity, genetic analysis (DNA isolation) results, the number and localization of past fractures, treatment methods, complications, hypermobility, and ambulation scoring. RESULTS The mean age of the patients (n=13 male, n=14 female) was 10.4±7.4 years, ranging from 3 to 39 years. Almost half (n=15, 55.6%) had consanguineous parents. The patients had 131 fractures during the 9 years between January 2011 and January 2020, with the femur being the most commonly fractured bone; 13 patients (48.15%) received surgical and conservative treatments, while the remaining 14 underwent only conservative treatments. The results revealed a strong association between the number of fractures and the types of genetic mutations (P=0.004). CONCLUSIONS Study findings indicate that the type of genetic mutation was not significantly correlated with the risk of treatment complications in osteogenesis imperfecta cases. Nevertheless, the study reveals a noteworthy association between the type of mutation and the number of surgeries required. Specifically, patients with the COL1A1 mutation needed more surgeries.

OBJECTIVE: With the availability of Next Generation Sequencing (NGS) diagnosis of genetic disorders has improved significantly. Its use is also applicable to ascertain diagnosis and management in a perinatal setting. The study aims to detect the genetic aetiology of various congenital structural and functional defects using NGS technology in the reproductive cohort at a tertiary centre. The secondary objective is to address challenges in the interpretation of variants.
METHODS: This was a retrospective study of couples who underwent exome sequencing (Mono-testing proband only or Duo-testing parents only or Trio-testing proband and parents) for suspected single gene disorders between years 2020-2022 at a tertiary care perinatal center in the South India. American College of Medical Genetics (ACMG) guidelines were followed to classify the pathogenicity of the variants identified by exome sequencing.
RESULTS: The overall diagnostic yield as defined by pathogenic/likely pathogenic variants obtained was (23/43) 53.4 %. The individual subsets have the following diagnostic yield viz., Mono 5/6 (83 %); Carrier 16/32 (50 %); Trio 2/5 (40 %). Diagnostic yield was significantly higher in consanguineous couples. However, miscarriage history, and organ system involvement did not have a significant effect on the diagnostic yield. Prenatal diagnosis was offered for seven patients based on the exome result. One fetus was confirmed with a compound heterozygous pathogenic variant.
CONCLUSIONS: Diagnostic yield of exome sequencing in our cohort was 53 %. The detection of pathogenic variants was maximum in those cases undergoing Mono exome sequencing. In places where there is a high prevalence of consanguinity and endogamy, NGS may be offered as first line test in the context of prenatal diagnosis.

Leber congenital amaurosis (LCA) and early-onset retinal degeneration (EORD) are inherited retinal diseases (IRD) characterized by early-onset vision impairment. Herein, we studied 15 Saudi families by whole exome sequencing (WES) and run-of-homozygosity (ROH) detection via AutoMap in 12/15 consanguineous families. This revealed (likely) pathogenic variants in 11/15 families (73%). A potential founder variant was found in RPGRIP1. Homozygous pathogenic variants were identified in known IRD genes (ATF6, CRB1, CABP4, RDH12, RIMS2, RPGRIP1, SPATA7). We established genotype-driven clinical reclassifications for ATF6, CABP4, and RIMS2. Specifically, we observed isolated IRD in the individual with the novel RIMS2 variant, and we found a retina-enriched RIMS2 isoform conserved but not annotated in mouse. The latter illustrates potential different phenotypic consequences of pathogenic variants depending on the particular tissue/cell-type specific isoforms they affect. Lastly, a compound heterozygous genotype in GUCY2D in one non-consanguineous family was demonstrated, and homozygous variants in novel candidate genes ATG2B and RUFY3 were found in the two remaining consanguineous families. Reporting these genes will allow to validate them in other IRD cohorts. Finally, the missing heritability of the two unsolved IRD cases may be attributed to variants in non-coding regions or structural variants that remained undetected, warranting future WGS studies.

Background: Congenital anomalies, representing structural or functional abnormalities present at birth, pose a substantial global health challenge, affecting 8 million newborns annually. With 3.3 million succumbing before age five and 3.2 million facing physical or mental disability, their diverse causes necessitate comprehensive understanding for effective healthcare planning. This study explores the prevalence of congenital anomalies among newborns in the Abha Maternity and Children Hospital (MCH) in Abha, Kingdom of Saudi Arabia. Methodology: A descriptive cross-sectional record-based study was conducted on newborns born between 2018 and 2022. Data were gathered in 4 months from September to December 2023. Purposive sampling was employed to select the case records of newborns with congenital anomalies after careful screening and considering inclusion and exclusion criteria. Data was acquired through a self-designed study tool, and the data were entered into Google Forms. Results: Congenital anomalies\' five-year prevalence was 3.21%, and one year, in 2022, the prevalence was 4.02%. Female neonates exhibited higher anomalies (59.3%), and preterm births accounted for 39.6%, emphasizing their vulnerability. The findings indicate that consanguineous marriages are linked to 63.3% of anomalies, notably neural tube defects (25%) and congenital heart diseases (19.7%). Anomalies are not significantly associated with consanguinity or birth order, but maternal age, education, employment, and antenatal maternal medical issues are associated considerably. Conclusions: These study insights contribute to health planners planning targeted interventions and awareness programs that are crucial to mitigate risks associated with preterm births and consanguineous marriages. The promotion of 100% antenatal screening and prophylactic medication for high-risk women and couples is necessary to prevent inherited deformities. In future the Ministry of Health must plan large-group prospective research to better understand the associated risk factors that will help public health initiatives minimize congenital-associated neonatal mortality and improve pregnancy outcomes.

UNASSIGNED: Infertility affects around 10-15% of couples worldwide and is both a social and medical problem. Parental consanguinity is considered to reduce fertility reserve. Consanguineous marriages, especially first cousin marriages, are very common in Oman according to the Oman National Health Survey data.
UNASSIGNED: This study aimed to determine whether women born to consanguineous parents have reduced ovarian reserve.
UNASSIGNED: This cohort study was conducted on 414 women aged ≤ 39, treated for infertility at Sultan Qaboos University hospital and Royal hospital, Muscat, Oman from January 2019-December 2020. Each participant was interviewed and a complete history, including parental consanguinity and physical examination, were recorded. On day 2 of the menstrual cycle, serum concentration of the following was performed: follicle-stimulating hormone (FSH), luteinizing hormone, estradiol, prolactin, thyroid stimulating hormone, and anti-Müllerian hormone (AMH). AMH was done, if necessary, on other days of the cycle. Antral follicle count (AFC) was done on day 2 and 3 of the menstrual cycle.
UNASSIGNED: Of the 414 women, parental consanguinity was present in 40.2% of couples. In women with low AFC, parental consanguinity was present in 15.3% compared to 13.0% in the non-consanguineous group. About 15% of women with low AMH had consanguineous parents, compared to 20.2% from the non-consanguineous group. High levels of FSH were present in 6.5% and 4.2% of the consanguineous and non-consanguineous groups, respectively. No significant difference was observed in AFC with reference to body mass index.
UNASSIGNED: The results from this study showed no statistically significant difference in low ovarian reserves (AFC, AMH, and FSH) in women whose parents had a consanguineous marriage.

BACKGROUND: Infantile-onset inflammatory bowel disease (IOIBD) is a gastrointestinal inflammatory condition often associated with monogenic disorders and is frequently caused by Interleukin-10 deficiencies. This study aimed to identify the mutation responsible for IBD in an 8-year-old patient from an Iranian family with consanguineous parents.
METHODS: Whole-exome sequencing (WES) was employed to identify disease-causing variations. Furthermore, we utilized integrated experimental data of HADDOCK molecular docking platform, including NMR spectroscopy, to characterize the mutant protein and elucidate the underlying functional mechanism of the identified mutation\'s pathogenicity.
RESULTS: Our findings revealed a novel 19-bp deletion mutation (c.25_43del, p.Leu9CysfsTer15) in the IL10RB gene. Sanger sequencing confirmed that this variant was inherited in homozygous state within this family, marking the first mutation identified in exon 1 of this gene. Molecular docking simulation demonstrated that the mutant form of IL10RB exhibited reduced affinity for binding to the Interleukin-10 ligand, leading to disruptions in downstream cellular signaling pathways.
CONCLUSIONS: The identification of this novel genetic variant as a causative factor for IOIBD highlights the clinical value of utilizing genetic testing, such as WES, as a reliable diagnostic approach for patients affected by this condition.

UNASSIGNED: Consanguinity represents a biological relationship between two individuals. In clinical genetics, it specifically refers to the marriage between individuals who are second cousins or closer. The aim of the study is to assess perceptions and their predictors among the Palestinian population towards consanguinity.
UNASSIGNED: A survey-based cross-sectional study was conducted. The sample was collected using convenience and snowball sampling methods, yielding a sample of 1008 participants. The perceptions towards consanguinity and its predictors were assessed using Chi-square test.
UNASSIGNED: The prevalence of consanguinity among married participants was 18.7% (N = 81/432), while it was 28.8% among their parents. Consanguinity rate was significantly low among the young age group (ie, <47 years old) and among participants whose mothers have undergraduate educational levels (P < 0.05). Other factors like parental consanguinity, educational level of participants, their father\'s educational level, and residency place showed no significant associations (P > 0.05). Rejection of consanguinity was significantly noted among young age participants, absence of parental consanguinity, the presence of children or family members with genetic disorders and female gender (P < 0.001). Furthermore, participants who indicated that they are governmental employees, those with 2000-5000 ILS monthly income, those who are married (P < 0.01), and those who indicated that their mothers are holders of postgraduate degree were significantly more likely to reject the idea of consanguinity (P < 0.05). Also, medical and/or scientific reasons were significantly associated with rejecting the idea of consanguinity (P < 0.001).
UNASSIGNED: Consanguinity prevalence has decreased among recent generations in Palestine, but it remains a significant challenge in Palestine. Therefore, educational and awareness programs about consanguinity and its health effects are effective strategies for reducing the consanguinity rate, especially for persons who are at the age of marriage.

OBJECTIVE: Monogenic diabetes is estimated to account for 1-6% of paediatric diabetes cases in primarily non-consanguineous populations, while the incidence and genetic spectrum in consanguineous regions are insufficiently defined. In this single-centre study we aimed to evaluate diabetes subtypes, obtain the consanguinity rate and study the genetic background of individuals with syndromic and neonatal diabetes in a population with a high rate of consanguinity.
METHODS: Data collection was carried out cross-sectionally in November 2021 at the paediatric diabetic clinic, Dr Jamal Ahmad Rashed Hospital, in Sulaimani, Kurdistan, Iraq. At the time of data collection, 754 individuals with diabetes (381 boys) aged up to 16 years were registered. Relevant participant data was obtained from patient files. Consanguinity status was known in 735 (97.5%) participants. Furthermore, 12 families of children with neonatal diabetes and seven families of children with syndromic diabetes consented to genetic testing by next-generation sequencing. Prioritised variants were evaluated using the American College of Medical Genetics and Genomics guidelines and confirmed by Sanger sequencing.
RESULTS: A total of 269 of 735 participants (36.5%) with known consanguinity status were offspring of consanguineous families. An overwhelming majority of participants (714/754, 94.7%) had clinically defined type 1 diabetes (35% of them were born to consanguineous parents), whereas only eight (1.1%) had type 2 diabetes (38% consanguineous). Fourteen (1.9%) had neonatal diabetes (50% consanguineous), seven (0.9%) had syndromic diabetes (100% consanguineous) and 11 (1.5%) had clinically defined MODY (18% consanguineous). We found that consanguinity was significantly associated with syndromic diabetes (p=0.0023) but not with any other diabetes subtype. The genetic cause was elucidated in ten of 12 participants with neonatal diabetes who consented to genetic testing (homozygous variants in GLIS3 [sibling pair], PTF1A and ZNF808 and heterozygous variants in ABCC8 and INS) and four of seven participants with syndromic diabetes (homozygous variants in INSR, SLC29A3 and WFS1 [sibling pair]). In addition, a participant referred as syndromic diabetes was diagnosed with mucolipidosis gamma and probably has type 2 diabetes.
CONCLUSIONS: This unique single-centre study confirms that, even in a highly consanguineous population, clinically defined type 1 diabetes is the prevailing paediatric diabetes subtype. Furthermore, a pathogenic cause of monogenic diabetes was identified in 83% of tested participants with neonatal diabetes and 57% of participants with syndromic diabetes, with most variants being homozygous. Causative genes in our consanguineous participants were markedly different from genes reported from non-consanguineous populations and also from those reported in other consanguineous populations. To correctly diagnose syndromic diabetes in consanguineous populations, it may be necessary to re-evaluate diagnostic criteria and include additional phenotypic features such as short stature and hepatosplenomegaly.