Identification of a Novel ARSA Gene Mutation Through High-Throughput Molecular Diagnosis Method in Two Girls with Late Infantile Metachromatic Leukodystrophy

Yari, Abolfazl; Vafaeie, Farzane; Karam, Zahra Miri; Hosseini, Mahya; Hashemzade, Hassan; Rahimi, Maryam Sadat; Ehsanbakhsh, Alireza; Miri-Moghaddam, Ebrahim

doi:10.1007/s12017-023-08757-y

Cited by 1 publication

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“…An increasing array of in silico tools has proven valuable in detecting disease‐associated deleterious mutations [ 20 , 21 , 22 , 23 ]. The potential impact of the variant on the protein was predicted using the Protein Variation Effect Analyzer (PROVEAN; https://jcvi.org/research/provean ) and MutationTaster 2021 ( https://genecascade.org/MutationTaster2021/ ).…”

Section: Methodsmentioning

confidence: 99%

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Identification of a Novel Deletion Variant (c.2999_3005delTGTGTGT/p.Asn1000SerfsTer4) in NPHP4 Associated With Nephronophthisis‐4

Miri Karam,

Gohari,

Khabaz

et al. 2024

Clinical Laboratory Analysis

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BackgroundNephronophthisis‐4 (NPHP4) is an inherited renal ciliopathy described by renal fibrosis and progressive impairment of kidney function. This study aimed to investigate the genetic basis and clinical manifestations of NPHP4 in two Iranian siblings.MethodsThe proband was a 27‐year‐old male with features of end‐stage renal disease, including anemia, uremia, polyuria, and polydipsia. It is worth mentioning that he has a 22‐year‐old sister with a similar presentation. Clinical diagnosis procedures, such as renal biopsy, brain imaging, blood and urine tests, cardiac evaluation, ophthalmic inspection, and auditory function assessment, were carried out to evaluate organ involvement and potential comorbidities. Whole‐exome sequencing (WES) and segregation analysis were performed to identify and confirm genetic variants associated with the condition. Computational variant analysis was conducted to evaluate the pathogenicity of the candidate variant. Furthermore, the SWISS‐MODEL server was utilized for protein modeling.ResultsThe brain, cardiac, ocular, and auditory functions were normal. Renal biopsy of the proband showed chronic interstitial inflammation and fibrosis. We found a novel homozygous 7‐base pair deletion (c.2999_3005delTGTGTGT/ p.Asn1000SerfsTer4) in exon 21 of NPHP4 by WES. Segregation analysis confirmed homozygosity for the NPHP4 variant in affected individuals and heterozygous carrier status in parents, supporting autosomal recessive inheritance. 3D protein modeling indicated significant structural changes due to the variant.ConclusionThis study expands the genetic causes and phenotypic spectrum of nephronophthisis‐4 and reveals the importance of genetic analysis in diagnosing and managing rare inherited kidney disorders, particularly those involving consanguinity.

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Section: Methodsmentioning

confidence: 99%

“…An increasing array of in silico tools has proven valuable in detecting disease-associated deleterious mutations [20][21][22][23].…”

Section: Evolutionary Conservation and In-silico Analysismentioning

confidence: 99%

Identification of a Novel Deletion Variant (c.2999_3005delTGTGTGT/p.Asn1000SerfsTer4) in NPHP4 Associated With Nephronophthisis‐4

Miri Karam,

Gohari,

Khabaz

et al. 2024

Clinical Laboratory Analysis

Self Cite

View full text Add to dashboard Cite

show abstract

Identification of a Novel ARSA Gene Mutation Through High-Throughput Molecular Diagnosis Method in Two Girls with Late Infantile Metachromatic Leukodystrophy

Cited by 1 publication

References 20 publications

Identification of a Novel Deletion Variant (c.2999_3005delTGTGTGT/p.Asn1000SerfsTer4) in NPHP4 Associated With Nephronophthisis‐4

Identification of a Novel Deletion Variant (c.2999_3005delTGTGTGT/p.Asn1000SerfsTer4) in NPHP4 Associated With Nephronophthisis‐4

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