A novel homozygous ALMS1 protein truncation
mutation (c.2938dupA) revealed variable clinical
expression among Saudi Alström syndrome patients

Bdier, Amnah Y.; Alqahtani, Faten; Verma, Prashant Kumar; Alshoaibi, Naeem A.; Alrayes, Nuha; Shaik, Noor Ahmad; Foo, Roger; Bhuiyan, Zahurul A.; Al‐Aama, Jumana Y.

doi:10.5114/aoms.2020.100635

Cited by 6 publications

(6 citation statements)

References 18 publications

(28 reference statements)

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“…The estimated incidence of the syndrome ranges from 1 in 500 000 to 1 in 1 000 000 9 . Approximately 1200 cases of alstrom syndrome have been identified worldwide 10 . The condition is equally common in both males and females 11 .…”

Section: Discussionmentioning

confidence: 99%

Alstrom syndrome with classical findings: a rare case report of monogenic ciliopathy co-occurrence in twins

Ghimire,

Simkhada,

Thapa

et al. 2024

Annals of Medicine &Amp; Surgery

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Introduction and Importance: Alstrom syndrome is one of the rarest monogenic ciliopathy belonging to autosomal recessive disorder. The pathophysiology of Alstrom syndrome is not well understood but based upon the available medical literature its mechanism can be linked with recessive mutation in ALSM1 gene resulting in various multiple organ involvement and poor prognosis. Moreover the co-occurrence of such syndrome simultaneously in twins in same period of time is considered rare. Case Presentation: Monochorionic diamniotic twins male born to healthy parents with significant antenatal and natal history along with decreased vision in both eyes in both twins since neonatal period. Throughout the childhood the disease progressed without any confirmatory diagnosis during which the twins underwent simultaneous multiple systemic involvement such as legal blindness in both twins at the age of 11 years, insulin resistance and features of diabetes mellitus, sensorineural hearing loss, subclinical hypothyroidism and various deranged metabolic panels. Certain diagnosis of Alstrom syndrome was made at the age of 16 years in both twins after whole exome sequencing. Clinical Discussion: Based on genetic profile alstrom syndrome is a unique diagnosis. Along with its multi organ involvement features, its progression and prognosis should also be looked upon while diagnosis and management in such syndromic patients. The diagnostic delay in such cases is also a matter of concern which can result in further delay in halting adverse effects of the disease itself. The multidisciplinary approach with involvement of endocrionologist, ophthalmologist and audiologist can bring upon improvement in quality of life of the patients. Conclusion: With the prevalence of 1 in million cases Alstrom Hallgren syndrome is one of the rare genetic disorder with poor prognosis. In our case we present classical findings in twins who were diagnosed as Alstrom syndrome concurrently and further diseases progressed simultaneously.

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Section: Discussionmentioning

confidence: 99%

Alstrom syndrome with classical findings: a rare case report of monogenic ciliopathy co-occurrence in twins

Ghimire,

Simkhada,

Thapa

et al. 2024

Annals of Medicine &Amp; Surgery

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“…worldwide. (11) The condition is equally common on both male and female. ( 12) Alstrome syndrome is caused by mutation in ALMS 1 gene which is located on short arm of chromosome number 2.…”

Section: Discussionmentioning

confidence: 99%

Alstrom Hallgren Syndrome With Classical Findings: A Rare Case Report of Monogenic Ciliopathy Co-Occurrence in Twins.

Ghimire,

simkhada,

Thapa

et al. 2023

Preprint

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“…We have initially used Human Splicing Finder (HSF), a publicly available web server ( http://www.umd.be/HSF/ ) to predict the impact of mutations on the strength of 5'ss, 3'ss, and branch splicing points. For predicting the impact of the mutation on ALMS1 RNA secondary structure, we used RNAfold web server ( http://rna.tbi.univie.ac.at/cgi-bin/RNAWebSuite/RNAfold.cgi ) ( 29 ), which uses the loop-based energy model and the dynamic programming algorithm for prediction of the linear or circular single-stranded RNA structure ( 16 ). The minimum free energy (MFE) value differences were compared to measure mutation-induced stability differences between wild-type and mutant secondary structures of ALMS1 and RNA molecules.…”

Section: Methodsmentioning

confidence: 99%

Identification of a Rare Exon 19 Skipping Mutation in ALMS1 Gene in Alström Syndrome Patients From Two Unrelated Saudi Families

et al. 2021

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Background: Alström syndrome (AS) is a very rare childhood disorder characterized by cardiomyopathy, progressive hearing loss and blindness. Inherited genetic variants of ALMS1 gene are the known molecular cause of this disease. The objective of this study was to characterize the genetic basis and understand the genotype–phenotype relationship in Saudi AS patients.Methods: Clinical phenotyping and whole-exome sequencing (WES) analysis were performed on six AS patients belonging to two unrelated consanguineous Saudi families. Sanger sequencing was performed to determine the mode of inheritance of ALMS1 variant in first-degree family relatives and also to ensure its rare prevalence in 100 healthy population controls.Results: We identified that Alström patients from both the families were sharing a very rare ALMS1, 3′-splice site acceptor (c.11873−2 A>T) variant, which skips entire exon-19 and shortens the protein by 80 amino acids. This disease variant was inherited by AS patients in autosomal recessive mode and is not yet reported in any population-specific genetic databases. AS patients carrying this mutation showed heterogeneity in clinical presentations. Computational analysis of the mutant centroid structure of ALMS1 mRNA revealed that exon-19 skipping enlarges the hairpin loop and decreases the free energy, eventually affecting its folding pattern, stability, and function. Hence, we propose c.11873–2A as an AS causative potential founder mutation in Saudi Arabia because it is found in two families lacking a common lineage.Conclusions: We conclude that WES analysis potentially helps in clinical phenotyping, early diagnosis, and better clinical management of Alström patients showing variable clinical expressivity.

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A novel homozygous ALMS1 protein truncation mutation (c.2938dupA) revealed variable clinical expression among Saudi Alström syndrome patients

Cited by 6 publications

References 18 publications

Alstrom syndrome with classical findings: a rare case report of monogenic ciliopathy co-occurrence in twins

Alstrom syndrome with classical findings: a rare case report of monogenic ciliopathy co-occurrence in twins

Alstrom Hallgren Syndrome With Classical Findings: A Rare Case Report of Monogenic Ciliopathy Co-Occurrence in Twins.

Identification of a Rare Exon 19 Skipping Mutation in ALMS1 Gene in Alström Syndrome Patients From Two Unrelated Saudi Families

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