Repository of mutations from Oman: The entry point to a national mutation database

Rajab, Anna; Hamza, Nishath; Harasi, Salma Al; Lawati, Fatma Al; Gibbons, Una; Alawi, Intesar Al; Kobus, Karoline; Hassan, Shermarke; Mahir, Ghariba; Salmi, Q. Al; Mons, Barend; Robinson, Peter N.

doi:10.12688/f1000research.6938.1

Cited by 11 publications

(10 citation statements)

References 19 publications

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“…National and ethnic specific mutation databases that may be used, for example, to facilitate the provision of genetic services, have been developed for a number of populations worldwide. Some examples include the Mediterranean Founder Mutation Database ( 28 ), the Omani National Genetic Database ( 29 ), the Israeli National Genetic Database ( 30 ), the Moroccan Genetic Disorders Database ( 31 ), and the Amish, Mennonite, and Hutterite Genetic Disorder Database ( 32 ).…”

Section: Introductionmentioning

confidence: 99%

Barriers and Considerations for Diagnosing Rare Diseases in Indigenous Populations

D’Angelo¹,

Hermes

McMaster

et al. 2020

Front. Pediatr.

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Advances in omics and specifically genomic technologies are increasingly transforming rare disease diagnosis. However, the benefits of these advances are disproportionately experienced within and between populations, with Indigenous populations frequently experiencing diagnostic and therapeutic inequities. The International Rare Disease Research Consortium (IRDiRC) multi-stakeholder partnership has been advancing toward the vision of all people living with a rare disease receiving an accurate diagnosis, care, and available therapy within 1 year of coming to medical attention. In order to further progress toward this vision, IRDiRC has created a taskforce to explore the access barriers to diagnosis of rare genetic diseases faced by Indigenous peoples, with a view of developing recommendations to overcome them. Herein, we provide an overview of the state of play of current barriers and considerations identified by the taskforce, to further stimulate awareness of these issues and the passage toward solutions. We focus on analyzing barriers to accessing genetic services, participating in genomic research, and other aspects such as concerns about data sharing, the handling of biospecimens, and the importance of capacity building.

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Section: Introductionmentioning

confidence: 99%

Barriers and Considerations for Diagnosing Rare Diseases in Indigenous Populations

D’Angelo¹,

Hermes

McMaster

et al. 2020

Front. Pediatr.

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“…Given that more than 50% of marriages in Oman are reported to be consanguineous unions, the prospect of this being a founder mutation cannot be ignored. 12 Hence, the detection of novel variants in rare disorders such as NS facilitates a targeted screening approach for quicker diagnosis in future cases.…”

Section: Discussionmentioning

confidence: 99%

A Novel SPINK5 Gene Mutation Associated with Netherton Syndrome in an Omani Patient

Hamza

Sukaiti

Ahmed

et al. 2021

Sultan Qaboos Univ Med J

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Netherton syndrome (NS) is an autosomal recessive primary immunodeficiency which is characterized by substantial skin barrier defects and is often misdiagnosed as severe atopic dermatitis or Hyper IgE syndrome. Although, over 80 pathogenic mutations in the SPINK5 gene have been reported worldwide in association with NS, only one NS-associated mutation has been reported in Arab populations to-date. This case report presents a novel association between the c.1887+1G>A mutation in the SPINK5 gene and NS in an Omani-Arab patient born in 2014. Accurate genetic diagnosis facilitated tailored clinical management of the index patient and enabled the provision of genetic counseling and offering of future reproductive options to the related individuals of the index patient. Keywords: Netherton syndrome, autosomal recessive, Serine Peptidase Inhibitor Kazal-Type 5, Congenital Ichthyosiform Erythroderma, genetics

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“…The custom of consanguineous marriages as well as within-tribe (endogamous) marriages are extremely conserved in Oman, accounting for 56.3% [ 38 ] and 20.4% of total marriages, respectively [ 39 ]. Over 300 genetic diseases have been identified in the Omani population [ 40 ]. The high frequency of recessive disorders in this population is probably related to a combination of genetic drift, consanguinity, and geographical isolation.…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic characteristics of autosomal recessive polycystic kidney disease in Oman

et al. 2020

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Background: There is a high prevalence of rare genetic disorders in the Middle East, and their study provides unique clinical and genetic insights. Autosomal recessive polycystic kidney disease (ARPKD) is one of the leading causes of kidney and liver-associated morbidity and mortality in Oman. We describe the clinical and genetic profile of cohort of ARPKD patients. Methods: We studied patients with a clinical diagnosis of ARPKD (n = 40) and their relatives (parents (n = 24) and unaffected siblings (n = 10)) from 32 apparently unrelated families, who were referred to the National Genetic Centre in Oman between January 2015 and December 2018. Genetic analysis of PKHD1 if not previously known was performed using targeted exon PCR of known disease alleles and Sanger sequencing. Results: A clinical diagnosis of ARPKD was made prenatally in 8 patients, 21 were diagnosed during infancy (0-1 year), 9 during early childhood (2-8 years) and 2 at later ages (9-13 years). Clinical phenotypes included polycystic kidneys, hypertension, hepatic fibrosis and splenomegaly. Twenty-four patients had documented chronic kidney disease (median age 3 years). Twenty-four out of the 32 families had a family history suggesting an autosomal recessive pattern of inherited kidney disease, and there was known consanguinity in 21 families (66%). A molecular genetic diagnosis with biallelic PKHD1 mutations was known in 18 patients and newly identified in 20 other patients, totalling 38 patients from 30 different families. Two unrelated patients remained genetically unsolved. The different PKHD1 missense pathogenic variants were: c.107C > T, p.(Thr36Met); c.406A > G, p.(Thr136Ala); c.4870C > T, p.(Arg1624Trp) and c.9370C > T, p.(His3124Tyr) located in exons 3, 6, 32 and 58, respectively. The c.406A > G, p.(Thr136Ala) missense mutation was detected homozygously in one family and heterozygously with a c.107C > T, p.(Thr36Met) allele in 5 other families. Overall, the most commonly detected pathogenic allele was c.107C > T; (Thr36Met), which was seen in 24 families. Conclusions: Molecular genetic screening of PKHD1 in clinically suspected ARPKD cases produced a high diagnostic rate. The limited number of PKHD1 missense variants identified in ARPKD cases suggests these may be common founder alleles in the Omani population. Cost effective targeted PCR analysis of these specific alleles can be a useful diagnostic tool for future cases of suspected ARPKD in Oman.

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Repository of mutations from Oman: The entry point to a national mutation database

Cited by 11 publications

References 19 publications

Barriers and Considerations for Diagnosing Rare Diseases in Indigenous Populations

Barriers and Considerations for Diagnosing Rare Diseases in Indigenous Populations

A Novel SPINK5 Gene Mutation Associated with Netherton Syndrome in an Omani Patient

Clinical and genetic characteristics of autosomal recessive polycystic kidney disease in Oman

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