Epidemiology and Outcome of CKD in Omani Children

Riyami, Mohamed S Al; Shehhi, Maryam Al; Sulaimi, Thuraiya Al; Mamary, Latifa Al; Maskari, Anisa Al; Ghaithi, Badria Al; Riyami, Marwa Al; Kalbani, Naifain Al; Saidi, Sulaiman Al

doi:10.1016/j.ekir.2019.02.014

Cited by 13 publications

(10 citation statements)

References 21 publications

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“…Inherited kidney diseases, including ARPKD are leading causes of CKD and ESKD in children in Oman, leading to signi cant morbidity and mortality. Previous studies from Oman have provided ARPKD-associated morbidity data but lacked molecular genetic data [10,14]. In this study we have provided a clinical and molecular genetic analysis of PKHD1 in a cohort of 40 patients, obtaining a molecular genetic diagnosis in 38 patients with clinically suspected ARPKD.…”

Section: Discussionmentioning

confidence: 99%

“…However, this number was from a selected hospital population and there are no population-based studies evaluating the incidence of ARPKD in the Omani population as a whole. A recent study from Oman showed that hereditary kidney disease accounts for 32% of etiologies causing chronic kidney disease (CKD) in children and ARPKD is the leading cause, accounting for of 12% of CKD [10]. The objective of this study was to investigate the clinical features and the molecular genetic diagnosis in patients with suspected ARPKD in an Omani population.…”

Section: Introductionmentioning

confidence: 99%

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Clinical and Genetic Characteristics of Autosomal Recessive Polycystic Kidney Disease in Oman

Alawi

Molinari

Salmi³

et al. 2020

Preprint

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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. 24 patients had documented chronic kidney disease (median age 3 years). 24 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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical and Genetic Characteristics of Autosomal Recessive Polycystic Kidney Disease in Oman

Alawi

Molinari

Salmi³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Inherited kidney diseases, including ARPKD are leading causes of CKD and ESKD in children in Oman, leading to significant morbidity and mortality. Previous studies from Oman have provided ARPKDassociated morbidity data but lacked molecular genetic data [10,14]. In this study we have provided a clinical and molecular genetic analysis of PKHD1 in a cohort of 40 patients, obtaining a molecular genetic diagnosis in 38 patients.…”

Section: Discussionmentioning

confidence: 99%

“…However, there are no population-based studies evaluating the incidence of ARPKD in the Omani population as a whole. A recent study from Oman showed that hereditary kidney disease accounts for 32% of etiologies causing chronic kidney disease (CKD) in children and ARPKD is the leading cause, accounting for of 12% of CKD [10]. The objective of this study was to demonstrate the utility of molecular genetic testing in patients with suspected ARPKD in an Omani population.…”

Section: Pathogenic Variants Have Been Identified In Multiple Unrelatmentioning

confidence: 98%

Clinical and Genetic Characteristics of Autosomal Recessive Polycystic Kidney Disease in Oman

Alawi

Molinari

Salmi³

et al. 2020

Preprint

View full text Add to dashboard Cite

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 was performed through next generation sequencing (NGS) 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. 24 patients had documented chronic kidney disease. 24 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 confirmed in 38 patients from 30 different families, giving a detection rate of 94%. Two unrelated patients remained genetically unsolved. In all of the solved cases, only four different PKHD1 missense pathogenic variants were identified: 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.Conclusion Molecular genetic screening of PKHD1 in clinically suspected ARPKD cases produced a high diagnostic rate. The four PKHD1 missense variants identified suggest there 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.

show abstract

“…However, this number was from a selected hospital population and there are no population-based studies evaluating the incidence of ARPKD in the Omani population as a whole. A recent study from Oman showed that hereditary kidney disease accounts for 32% of etiologies causing chronic kidney disease (CKD) in children and ARPKD is the leading cause, accounting for 12% of CKD [10]. The objective of this study was to investigate the clinical features and the molecular genetic diagnosis in patients with suspected ARPKD in an Omani population.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

Epidemiology and Outcome of CKD in Omani Children

Cited by 13 publications

References 21 publications

Clinical and Genetic Characteristics of Autosomal Recessive Polycystic Kidney Disease in Oman

Clinical and Genetic Characteristics of Autosomal Recessive Polycystic Kidney Disease in Oman

Clinical and Genetic Characteristics of Autosomal Recessive Polycystic Kidney Disease in Oman

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

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