A novel homozygous nonsense mutation in CCDC88A gene cause PEHO-like syndrome in consanguineous Saudi family

Abdulkareem, Angham Abdulrahman; Abulnaja, Khalid O.; Jan, Mohammad M.; Karim, Sajjad; Rasool, Mahmood; Ansari, Shakeel Ahmed; Chaudhary, Adeel G.; Al-Qahtani, Mohammad H.; Naseer, Muhammad Imran

doi:10.1007/s10072-018-3626-5

Cited by 13 publications

(15 citation statements)

References 13 publications

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“…During last few years, five other genes (KIF1A, CCDC88A, GNAO1, CDKL5 and PRUNE1) has been described to cause PEHO or PEHO-like syndrome (Abdulkareem et al, 2019;Gawlinski et al, 2016;Langlois et al, 2016;Nahorski et al, 2016;Zollo et al, 2017). De novo disease-causing variants in KIF1A were first described as causing PEHO syndrome, but with large phenotypic variability even in patients with the same variants (Langlois et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Soon after that, Nahorski et al described a consanguineous family of British origin with three children born with features of PEHO syndrome and a homozygous frameshift mutation in CCDC88A gene (Nahorski et al, 2016). Quite recently, another consanguineous family with a novel homozygous nonsense mutation of the CCDC88A gene causing PEHO-like syndrome was published (Abdulkareem et al, 2019). It has also recently been hypothesized that PEHO and PEHO-like syndrome may represent a severe end of the spectrum of the early-onset encephalopathies (Gawlinski et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

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PEHO syndrome caused by compound heterozygote variants in ZNHIT3 gene

Õunap

Muru

Õiglane-Shlik

et al. 2020

European Journal of Medical Genetics

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PEHO syndrome is characterized by Progressive Encephalopathy with Edema, Hypsarrhythmia, and Optic atrophy, which was first described in Finnish patients. A homozygous missense substitution p.Ser31Leu in ZNHIT3 was recently identified as the primary cause of PEHO syndrome in Finland. Variants in ZNHIT3 have not been identified in patients with PEHO or PEHO-like syndrome in other populations. It has therefore been suggested that PEHO syndrome caused by ZNHIT3 variants does not occur outside of the Finnish population. We describe the first patient outside Finland who carries compound heterozygous variants in ZNHIT3 gene causing PEHO syndrome. Trio genome sequencing was carried out and the identified variants were confirmed by Sanger sequencing. The patient filled all diagnostic clinical criteria of PEHO syndrome. We identified biallelic missense variants in ZNHIT3 gene: the c.92C>T p.( Ser31Leu) variant (NM_004773.3), which is described previously as causing PEHO syndrome and the second novel variant c.41G>T p.(Cys14Phe). There are only eight heterozygous carriers of c.41G>T

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

PEHO syndrome caused by compound heterozygote variants in ZNHIT3 gene

Õunap

Muru

Õiglane-Shlik

et al. 2020

European Journal of Medical Genetics

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“…Blood from the patients recruited for this study was collected in the center after having the informed written consent signed by the patient or guardians in case children were involved in the study. DNA was extracted from blood stored in the EDTA tubes (Roche Life Science), as previously described ( 19 ) until further use for DNA extraction. The concentration of DNA was measured by using Nanodrop TM 2000/2000c spectrophotometers (Thermo Fisher Scientific Waltham, Massachusetts, USA).…”

Section: Methodsmentioning

confidence: 99%

Whole-Exome Sequencing Identifies Novel SCN1A and CACNB4 Genes Mutations in the Cohort of Saudi Patients With Epilepsy

Naseer

Abdulkareem²,

Rasool³

et al. 2022

Front. Pediatr.

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Epilepsy is a neurological disorder described as recurrent seizures mild to severe convulsions along with conscious loss. There are many different genetic anomalies or non-genetic conditions that affect the brain and cause epilepsy. The exact cause of epilepsy is unknown so far. In this study, whole-exome sequencing showed a family having novel missense variant c.1603C>T, p. Arg535Cys in exon 10 of Sodium Voltage-Gated Channel Alpha Subunit 1 (SCN1A) gene. Moreover, targeted Sanger sequencing analysis showed c.1212A>G p.Val404Ile in SCN1A gene in 10 unrelated patients and a mutation in Calcium Voltage-Gated Channel Auxiliary Subunit Beta 4 gene where one base pair insertion of “G” c.78_79insG, p.Asp27Glyfs*26 in the exon 3 in three different patients were observed from the cohort of 25 epileptic sporadic cases. The insertion changes the amino acid sequence leading to a frameshift mutation. Here, we have described, for the first time, three novel mutations that may be associated with epilepsy in the Saudi population. The study not only help us to identify the exact cause of genetic variations causing epilepsy whereas but it would also eventually enable us to establish a database to provide a foundation for understanding the critical genomic regions to control epilepsy in Saudi patients.

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“…This study was approved by the local ethical committee of CEGMR, King Abdulaziz University (ethical approval number:013-CEGMR-02-ETH) and followed all the guidelines according to the Declaration of Helsinki 2013. DNA was extracted from the blood samples (Roche Life Science), as previously described ( 13 ). A detailed family pedigree was drawn after obtaining information from the family members, as shown in Figure 1 .…”

Section: Methodsmentioning

confidence: 99%

Next-Generation Sequencing Reveals Novel Homozygous Missense Variant c.934T > C in POLR1C Gene Causing Leukodystrophy and Hypomyelinating Disease

et al. 2022

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Leukodystrophies are a diverse group of genetically established disorders categorized by unusual white matter changes on brain imaging. Hypomyelinating leukodystrophies (HLDs) are a group of neurodevelopmental disorders that affect myelin sheath development in the brain. These disorders are categorized as developmental delay, spasticity, hypotonia, and intellectual disabilities. We describe a patient with developmental delay, cerebellar ataxia, spasticity, hypotonia, and intellectual disability from a healthy family member. Whole exome sequencing (WES) was performed to identify causative variants, which were further analyzed by bioinformatic analysis. WES was performed, and Sanger sequencing-based segregation analysis confirmed the presence of the homozygous missense variants of NM_203290.3 c.934T > C p.Ser312Pro of RNA polymerase I and III subunit C (POLR1C) gene in this patient and heterozygous variant in the unaffected carrier father and mother, supporting the pathogenicity and inheritance pattern of this variant. Furthermore, the variant identified by WES was validated in healthy controls (n = 100) using Sanger sequencing analysis. Finally, our study explained the important use of WES in disease diagnosis and provided further evidence that the variant in the POLR1C gene may play an important role in the development of hypomyelinating leukodystrophy in Saudi families.

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A novel homozygous nonsense mutation in CCDC88A gene cause PEHO-like syndrome in consanguineous Saudi family

Cited by 13 publications

References 13 publications

PEHO syndrome caused by compound heterozygote variants in ZNHIT3 gene

PEHO syndrome caused by compound heterozygote variants in ZNHIT3 gene

Whole-Exome Sequencing Identifies Novel SCN1A and CACNB4 Genes Mutations in the Cohort of Saudi Patients With Epilepsy

Next-Generation Sequencing Reveals Novel Homozygous Missense Variant c.934T > C in POLR1C Gene Causing Leukodystrophy and Hypomyelinating Disease

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