Detection of an FYCO1 nonsense mutation in an affected patient with autosomal recessive cataract (CTRCT18): a case report

Al-Badran, Raed Abdulelah; Al-Badran, Adnan Issa; Mabudi, Hadideh; Neissi, Mostafa; Mohammadi-Asl, Javad

doi:10.1186/s43042-022-00272-2

Cited by 3 publications

(4 citation statements)

References 11 publications

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“…It has been comprehended that nearly 15% of FYCO1 genetic variants contributed to overall rates of autosomal recessive CC [ 8 ]. In near recent reports, FYCO1 mutations detected in different ethnic groups include c.1387 G > T [ 13 ]; p.Gly463Ter; c.1621C > T [ 15 ]; p. Gln541Ter; and c.2365 C>T [ 14 ]. On the other hand, the largest exon 10 deletion and splice-site variant is c.3150 + 1G>T [ 14 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…In 50-63% of CC, the etiology is idiopathic, while 30% are monogenic with autosomal dominant pattern [ 12 ]. To date, more than 1400 etiologic variations have been described for this disease [ 11 , 13 , 14 , 15 , 16 ]. Non-syndromic cataract is linked to 39 causative genes or loci.…”

Section: Introductionmentioning

confidence: 99%

“…The mutations associated with FYCO1 are the most frequent in Pakistani families with cataracts and contribute about 14% to the total genetic load in this population. The common nonsense mutation p.Gln736Ter (Q736X) has been reported in Egyptian, Iranian, and Pakistani children with CC [ 13 , 16 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

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Identification and Functional Characterization of Mutation in FYCO1 in Families with Congenital Cataract

Ullah,

Rehman,

Dad

et al. 2023

Life

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Congenital cataract (CC) causes a third of the cases of treatable childhood blindness worldwide. CC is a disorder of the crystalline lens which is established as clinically divergent and has complex heterogeneity. This study aimed to determine the genetic basis of CC. Whole blood was obtained from four consanguineous families with CC. Genomic DNA was extracted from the blood, and the combination of targeted and Sanger sequencing was used to identify the causative gene. The mutations detected were analyzed in silico for structural and protein–protein interactions to predict their impact on protein activities. The sequencing found a known FYCO1 mutation (c.2206C>T; p.Gln736Term) in autosomal recessive mode in families with CC. Co-segregation analysis showed affected individuals as homozygous and carriers as heterozygous for the mutation and the unaffected as wild-type. Bioinformatics tools uncovered the loss of the Znf domain and structural compactness of the mutant protein. In conclusion, a previously reported nonsense mutation was identified in four consanguineous families with CC. Structural analysis predicted the protein as disordered and coordinated with other structural proteins. The autophagy process was found to be significant for the development of the lens and maintenance of its transparency. The identification of these markers expands the scientific knowledge of CC; the future goal should be to understand the mechanism of disease severity. Ascertaining the genetic etiology of CC in a family member facilitates establishing a molecular diagnosis, unlocks the prospect of prenatal diagnosis in pregnancies, and guides the successive generations by genetic counseling.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification and Functional Characterization of Mutation in FYCO1 in Families with Congenital Cataract

Ullah,

Rehman,

Dad

et al. 2023

Life

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“…Out of the 19 mutations reported so far in FYCO1 for congenital cataract mostly are responsible for the formation of truncated protein hampered with coiled–coil or GOLD domain of the protein (Iqbal et al, 2020 ). Recently reported mutations in FYCO1 include c.2365 C > T (Aprahamian et al, 2021 ), (c.1621C > T; p. Gln541* (Barashkov et al, 2021 ) and (c.1387 G > T; p.G463X) (Al‐Badran et al, 2022 ). Among all these, this is the first longest deletion reported so far in FYCO1 gene and 2nd reported splice site variant for Exon 10 in addition to previously reported splice site variant (c.3150 + 1G > T) (Chen et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Targeted gene sequencing of FYCO1 identified a novel mutation in a Pakistani family for autosomal recessive congenital cataract

Saleem

Siddiqui²,

Irshad

et al. 2022

Molec Gen & Gen Med

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Background Congenital cataract is causing one‐third of blindness worldwide. Congenital cataract is heterogeneous in its inheritance patterns. The current study is aimed to explore the unknown genetic causes underlying congenital cataracts. Methods Blood samples from affected and normal individuals of n = 25 Pakistani families identified with congenital cataracts were collected. Genomic DNA was extracted and Sanger sequencing was performed to identify novel pathogenic variants in the FYCO1 (MIM#607182) gene. Later structural bioinformatics tools and molecular dynamics simulations were performed to analyze the impact of these variants on protein structure and function. Results Sanger sequencing resulted in the identification of a novel splice site mutation (NM_024513.3: c.3151‐29_3151‐7del) segregating in an autosomal recessive manner. This novel variant was confirmed to be absent in the n = 300 population controls. Further, bioinformatics tools revealed the formation of a mutant protein with a loss of the Znf domain. In addition, we also found a previously known (c.4127 T > C; p.Leu1376Pro) mutation in four families. We also report a novel heterozygous variant (c.3419G > A; p.Arg1140Gln) in another family. Conclusions In conclusion, we report a novel deletion (NM_024513.3: c.3151‐29_3151‐7del) in one family and a frequent homozygous missense mutation (c.4127 T > C; p.Leu1376Pro) in four Pakistani families. The current research highlights the importance of autophagy in lens development and maintaining its transparency.

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Identification and characterization of NMNAT1 gene mutations in an Iranian patient with Leber congenital amaurosis 9

Neissi,

Sheikh‐Hosseini,

Mohammadi‐Asl

et al. 2024

Clinical Case Reports

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Key Clinical MessageThe discovery of compound heterozygous NMNAT1 mutations (c.245T>C; p.Val82Ala and c.575A>G; p.Asp192Gly) provides a genetic explanation for Leber congenital amaurosis 9 in an Iranian patient. The proband's symptoms—including severe visual impairment, nystagmus, night blindness, and retinal degeneration—align with Leber congenital amaurosis 9 clinical features. This case underscores the value of exome‐sequencing in diagnosing rare genetic disorders and highlights its role in guiding personalized genetic counseling and potential treatments.AbstractLeber congenital amaurosis is a severe early‐onset inherited retinal dystrophy. This study delves into the genetic basis of Leber congenital amaurosis, pinpointing compound heterozygous mutations in the NMNAT1 gene as significant causative factors. While one mutation validates previous findings (c.245T>C; p.Val82Ala), the second (c.575A>G; p.Asp192Gly) proves novel, expanding the genetic landscape of Leber congenital amaurosis 9. Both mutations, inherited independently from nonconsanguineous parents, contribute to the intricate genetic basis of light on Leber congenital amaurosis 9 in this case. The identified mutations shed light on Leber congenital amaurosis genetics in the Iranian population, showcasing the efficacy of exome‐sequencing for molecular diagnoses in hereditary retinal degeneration. These findings provide valuable insights for tailored genetic counseling and potential therapeutic interventions.

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Detection of an FYCO1 nonsense mutation in an affected patient with autosomal recessive cataract (CTRCT18): a case report

Cited by 3 publications

References 11 publications

Identification and Functional Characterization of Mutation in FYCO1 in Families with Congenital Cataract

Identification and Functional Characterization of Mutation in FYCO1 in Families with Congenital Cataract

Targeted gene sequencing of FYCO1 identified a novel mutation in a Pakistani family for autosomal recessive congenital cataract

Identification and characterization of NMNAT1 gene mutations in an Iranian patient with Leber congenital amaurosis 9

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