TY - JOUR
T1 - Identification and Functional Characterization of Mutation in FYCO1 in Families with Congenital Cataract
AU - Ullah, Muhammad Ikram
AU - Rehman, Zaira
AU - Dad, Rubina
AU - Alsrhani, Abdullah
AU - Shakil, Muhammad
AU - Ghanem, Heba Bassiony
AU - Alameen, Ayman Ali Mohammed
AU - Elsadek, Mohamed Farouk
AU - Eltayeb, Lienda Bashier
AU - Ullah, Sajjad
AU - Atif, Muhammad
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/8
Y1 - 2023/8
N2 - 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.
AB - 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.
KW - FYCO1
KW - congenital cataract
KW - consanguineous families
KW - in silico analysis
KW - mutations
UR - http://www.scopus.com/inward/record.url?scp=85169067709&partnerID=8YFLogxK
U2 - 10.3390/life13081788
DO - 10.3390/life13081788
M3 - Article
AN - SCOPUS:85169067709
SN - 2075-1729
VL - 13
JO - Life
JF - Life
IS - 8
M1 - 1788
ER -