The neuronal ceroid lipofuscinoses type 8 (CLN8) gene mutations: A new compound heterozygous case and the protein's bioinformatic analyses
Muhammad Mahajnah, Rajech Sharkia, Abdelnaser Zalan, Hazar Zahalkah
Objective The neuronal ceroid lipofuscinoses diseases, manifested primarily by seizures, ataxia, progressive visual loss, and mental decline. Ten clinical subtypes with eight distinctive genes and heterogeneous clinical manifestations been observed. The vast majority of CLN8 patients caused by homozygotes recessive mutations of the CLN8 genes. Only Individual cases of CLN8 patients reported with compound heterozygous mutations. In the current study, we report two patients presenting with atypical protracted clinical course of CLN8 carrying a novel compound heterozygous mutation at the CLN8 gene. Bioinformatics' analyses of the CLN8 gene mutations was simulated, and their consequences on the protein structure discussed.
Methods DNA was extracted from peripheral blood lymphocytes of two patients and all family members using standard procedures. We predicted the structure of the protein using the state-of-the-art algorithm AlphaFold and obtained a model with very high prediction confidence. This model, as well as other bioinformatics tools, were then used to analyze the mutations.
Results Both girls are carriers to the missense known mutation (763C>G) they inherited maternally. Whole exome sequencing of CLN8 gene revealed the presence of an additional mutation (G; P Gln256Glu<NM_018941.3: c.766C), which was interpreted as " Likely pathogenic " and inherited paternally. Analysis our patients mutations reveled that these mutations cause of inactive protein production
Conclusions: Compound heterozygous mutations of the CLN8 gene may be an etiology of mild and protracted clinical course of CLN8. Gene structural and functional analysis is important in order to understand the basic pathophysiology of CLN8 disease.
Keywords: Neuronal ceroid lipofuscinoses, CLN8, compound heterozygous
Muhammad Mahajnah
Hillel Yaffe Medical Center
Israel
Rajech Sharkia
The Triangle Regional Research and Development Center, Kfar Qara, Israel.
Israel
Abdelnaser Zalan
The Triangle Regional Research and Development Center, Kfar Qara, Israel
Israel
Hazar Zahalkah
Hillel Yaffe Medical Center
Israel
Objective The neuronal ceroid lipofuscinoses diseases, manifested primarily by seizures, ataxia, progressive visual loss, and mental decline. Ten clinical subtypes with eight distinctive genes and heterogeneous clinical manifestations been observed. The vast majority of CLN8 patients caused by homozygotes recessive mutations of the CLN8 genes. Only Individual cases of CLN8 patients reported with compound heterozygous mutations. In the current study, we report two patients presenting with atypical protracted clinical course of CLN8 carrying a novel compound heterozygous mutation at the CLN8 gene. Bioinformatics' analyses of the CLN8 gene mutations was simulated, and their consequences on the protein structure discussed.
Methods DNA was extracted from peripheral blood lymphocytes of two patients and all family members using standard procedures. We predicted the structure of the protein using the state-of-the-art algorithm AlphaFold and obtained a model with very high prediction confidence. This model, as well as other bioinformatics tools, were then used to analyze the mutations.
Results Both girls are carriers to the missense known mutation (763C>G) they inherited maternally. Whole exome sequencing of CLN8 gene revealed the presence of an additional mutation (G; P Gln256Glu<NM_018941.3: c.766C), which was interpreted as " Likely pathogenic " and inherited paternally. Analysis our patients mutations reveled that these mutations cause of inactive protein production
Conclusions: Compound heterozygous mutations of the CLN8 gene may be an etiology of mild and protracted clinical course of CLN8. Gene structural and functional analysis is important in order to understand the basic pathophysiology of CLN8 disease.
Keywords: Neuronal ceroid lipofuscinoses, CLN8, compound heterozygous
Muhammad Mahajnah
Hillel Yaffe Medical Center
Israel
Rajech Sharkia
The Triangle Regional Research and Development Center, Kfar Qara, Israel.
Israel
Abdelnaser Zalan
The Triangle Regional Research and Development Center, Kfar Qara, Israel
Israel
Hazar Zahalkah
Hillel Yaffe Medical Center
Israel
Muhammad Mahajnah
Hillel Yaffe Medical Center Israel
Hillel Yaffe Medical Center Israel