Novel variants underlying autosomal recessive intellectual disability in Pakistani consanguineous families
Abstract Background Intellectual disability (ID) is both a clinically diverse and genetically heterogeneous group of disorder, with an onset of cognitive impairment before the age of 18 years. ID is characterized by significant limitations in intellectual functioning and adaptive behaviour. The iden...
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| Format: | Article |
| Language: | English |
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BMC
2020-03-01
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| Series: | BMC Medical Genetics |
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| Online Access: | http://link.springer.com/article/10.1186/s12881-020-00998-z |
| _version_ | 1819168766776311808 |
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| author | Muhammad Ilyas Stephanie Efthymiou Vincenzo Salpietro Nuzhat Noureen Faisal Zafar Sobiah Rauf Asif Mir Henry Houlden |
| author_facet | Muhammad Ilyas Stephanie Efthymiou Vincenzo Salpietro Nuzhat Noureen Faisal Zafar Sobiah Rauf Asif Mir Henry Houlden |
| author_sort | Muhammad Ilyas |
| collection | DOAJ |
| description | Abstract Background Intellectual disability (ID) is both a clinically diverse and genetically heterogeneous group of disorder, with an onset of cognitive impairment before the age of 18 years. ID is characterized by significant limitations in intellectual functioning and adaptive behaviour. The identification of genetic variants causing ID and neurodevelopmental disorders using whole-exome sequencing (WES) has proven to be successful. So far more than 1222 primary and 1127 candidate genes are associated with ID. Methods To determine pathogenic variants causative of ID in three unrelated consanguineous Pakistani families, we used a combination of WES, homozygosity-by-descent mapping, de-deoxy sequencing and bioinformatics analysis. Results Rare pathogenic single nucleotide variants identified by WES which passed our filtering strategy were confirmed by traditional Sanger sequencing and segregation analysis. Novel and deleterious variants in VPS53, GLB1, and MLC1, genes previously associated with variable neurodevelopmental anomalies, were found to segregate with the disease in the three families. Conclusions This study expands our knowledge on the molecular basis of ID as well as the clinical heterogeneity associated to different rare genetic causes of neurodevelopmental disorders. This genetic study could also provide additional knowledge to help genetic assessment as well as clinical and social management of ID in Pakistani families. |
| first_indexed | 2024-12-22T19:08:50Z |
| format | Article |
| id | doaj.art-e12db3ed56af4fa8b96452f503099b00 |
| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-22T19:08:50Z |
| publishDate | 2020-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genetics |
| spelling | doaj.art-e12db3ed56af4fa8b96452f503099b002022-12-21T18:15:44ZengBMCBMC Medical Genetics1471-23502020-03-012111810.1186/s12881-020-00998-zNovel variants underlying autosomal recessive intellectual disability in Pakistani consanguineous familiesMuhammad Ilyas0Stephanie Efthymiou1Vincenzo Salpietro2Nuzhat Noureen3Faisal Zafar4Sobiah Rauf5Asif Mir6Henry Houlden7Department of Biological Sciences, International Islamic University IslamabadDepartment of Neuromuscular Disorders, UCL Institute of NeurologyDepartment of Neuromuscular Disorders, UCL Institute of NeurologyDepartment of Pediatric Neurology, Children’s Hospital and Institute of Child HealthDepartment of Pediatric Neurology, Children’s Hospital and Institute of Child HealthNational Center for Bioinformatics, Quaid-i-Azam UniversityDepartment of Biological Sciences, International Islamic University IslamabadDepartment of Neuromuscular Disorders, UCL Institute of NeurologyAbstract Background Intellectual disability (ID) is both a clinically diverse and genetically heterogeneous group of disorder, with an onset of cognitive impairment before the age of 18 years. ID is characterized by significant limitations in intellectual functioning and adaptive behaviour. The identification of genetic variants causing ID and neurodevelopmental disorders using whole-exome sequencing (WES) has proven to be successful. So far more than 1222 primary and 1127 candidate genes are associated with ID. Methods To determine pathogenic variants causative of ID in three unrelated consanguineous Pakistani families, we used a combination of WES, homozygosity-by-descent mapping, de-deoxy sequencing and bioinformatics analysis. Results Rare pathogenic single nucleotide variants identified by WES which passed our filtering strategy were confirmed by traditional Sanger sequencing and segregation analysis. Novel and deleterious variants in VPS53, GLB1, and MLC1, genes previously associated with variable neurodevelopmental anomalies, were found to segregate with the disease in the three families. Conclusions This study expands our knowledge on the molecular basis of ID as well as the clinical heterogeneity associated to different rare genetic causes of neurodevelopmental disorders. This genetic study could also provide additional knowledge to help genetic assessment as well as clinical and social management of ID in Pakistani families.http://link.springer.com/article/10.1186/s12881-020-00998-zIntellectual disabilityVPS53 geneGLB1 geneMLC1 geneWhole exome sequencing |
| spellingShingle | Muhammad Ilyas Stephanie Efthymiou Vincenzo Salpietro Nuzhat Noureen Faisal Zafar Sobiah Rauf Asif Mir Henry Houlden Novel variants underlying autosomal recessive intellectual disability in Pakistani consanguineous families BMC Medical Genetics Intellectual disability VPS53 gene GLB1 gene MLC1 gene Whole exome sequencing |
| title | Novel variants underlying autosomal recessive intellectual disability in Pakistani consanguineous families |
| title_full | Novel variants underlying autosomal recessive intellectual disability in Pakistani consanguineous families |
| title_fullStr | Novel variants underlying autosomal recessive intellectual disability in Pakistani consanguineous families |
| title_full_unstemmed | Novel variants underlying autosomal recessive intellectual disability in Pakistani consanguineous families |
| title_short | Novel variants underlying autosomal recessive intellectual disability in Pakistani consanguineous families |
| title_sort | novel variants underlying autosomal recessive intellectual disability in pakistani consanguineous families |
| topic | Intellectual disability VPS53 gene GLB1 gene MLC1 gene Whole exome sequencing |
| url | http://link.springer.com/article/10.1186/s12881-020-00998-z |
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