Neurological and extra-neurological clinical spectrum observed in pediatric patients with EMC1 gene variants identified by whole exome sequencing
Background: The endoplasmic reticulum membrane protein complex 1 (EMC1) gene encodes a subunit of the EMC with multiple alternatively spliced transcripts encoding different isoforms. Monoallelic and biallelic mutations of the EMC1 gene have been reported for cerebellar atrophy, visual impairment, ps...
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| Format: | Article |
| Language: | English |
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Discover STM Publishing Ltd
2021-12-01
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| Series: | Journal of Biochemical and Clinical Genetics |
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| Online Access: | http://www.ejmanager.com/fulltextpdf.php?mno=22311 |
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| author | Abdul Ali Peer-Zada Osama A. Obaid Manar A. Samman Aqeela AlHashim Hajar AlAsmari Ali M. AlAsmari |
| author_facet | Abdul Ali Peer-Zada Osama A. Obaid Manar A. Samman Aqeela AlHashim Hajar AlAsmari Ali M. AlAsmari |
| author_sort | Abdul Ali Peer-Zada |
| collection | DOAJ |
| description | Background: The endoplasmic reticulum membrane protein complex 1 (EMC1) gene encodes a subunit of the EMC with multiple alternatively spliced transcripts encoding different isoforms. Monoallelic and biallelic mutations of the EMC1 gene have been reported for cerebellar atrophy, visual impairment, psychomotor retardation, lipoid proteinosis of Urbach and Wiethe, and Alkuraya-Kucinskas syndrome.
Objectives: Herein, we present whole exome sequencing results of eight Saudi pediatric patients with distinctive clinical features which revealed both monoallelic and biallelic variants in the EMC1 gene (CHR1 exon4:19568918, NM_001271429.2, c.364G>A; p.A122T), including two previously reported siblings (CHR1 exon21:19547328, NM_015047.3, c.2602G>A; p.G868R).
Results: The patients presented with the neurological and extra-neurological clinical spectrum that included seizures, spastic diplegia, cognitive impairment, axial and appendicular hypotonia, dysmorphic features, joint hyper-flexibility, attention deficit hyperactivity disorder, skeletal dysplasia in addition to generalized global developmental delay, failure to thrive, speech delay, intellectual disability, and visual impairments. Furthermore, brain Magnetic resonance imaging findings were consistent with variable clinical features and revealed brain atrophy, thinning of corpus callosum, semi-lobar holoprosencephaly, white matter abnormality, diffuse paucity of the myelin within the brain parenchyma, and reduction of white matter arborization in the temporal lobes.
Conclusion: In conclusion, these clinical cases highlight the importance of the EMC1 gene in disease phenotype and add up to the expanded EMC1-related phenotype. [JBCGenetics 2021; 4(2.000): 93-99] |
| first_indexed | 2024-03-13T08:41:36Z |
| format | Article |
| id | doaj.art-f9ca8474c87f4b7d87e897d5d69f7891 |
| institution | Directory Open Access Journal |
| issn | 1658-807X |
| language | English |
| last_indexed | 2024-03-13T08:41:36Z |
| publishDate | 2021-12-01 |
| publisher | Discover STM Publishing Ltd |
| record_format | Article |
| series | Journal of Biochemical and Clinical Genetics |
| spelling | doaj.art-f9ca8474c87f4b7d87e897d5d69f78912023-05-30T11:50:34ZengDiscover STM Publishing LtdJournal of Biochemical and Clinical Genetics1658-807X2021-12-0142939910.24911/JBCGenetics/183-160386342622311Neurological and extra-neurological clinical spectrum observed in pediatric patients with EMC1 gene variants identified by whole exome sequencingAbdul Ali Peer-Zada0Osama A. Obaid1Manar A. Samman2Aqeela AlHashim3Hajar AlAsmari4Ali M. AlAsmari5Pathology and Clinical Laboratory Medicine Administration, Section of Molecular Pathology, King Fahad Medical City, Riyadh, Saudi Arabia Section of Medical Genetics, Children's Hospital, King Fahad Medical City, Riyadh, Saudi Arabia Pathology and Clinical Laboratory Medicine Administration, Section of Molecular Pathology, King Fahad Medical City, Riyadh, Saudi Arabia Pediatric Neurology, King Fahad Medical City, Riyadh, Saudi Arabia Section of Medical Genetics, Children's Hospital, King Fahad Medical City, Riyadh, Saudi Arabia Section of Medical Genetics, Children's Hospital, King Fahad Medical City, Riyadh, Saudi ArabiaBackground: The endoplasmic reticulum membrane protein complex 1 (EMC1) gene encodes a subunit of the EMC with multiple alternatively spliced transcripts encoding different isoforms. Monoallelic and biallelic mutations of the EMC1 gene have been reported for cerebellar atrophy, visual impairment, psychomotor retardation, lipoid proteinosis of Urbach and Wiethe, and Alkuraya-Kucinskas syndrome. Objectives: Herein, we present whole exome sequencing results of eight Saudi pediatric patients with distinctive clinical features which revealed both monoallelic and biallelic variants in the EMC1 gene (CHR1 exon4:19568918, NM_001271429.2, c.364G>A; p.A122T), including two previously reported siblings (CHR1 exon21:19547328, NM_015047.3, c.2602G>A; p.G868R). Results: The patients presented with the neurological and extra-neurological clinical spectrum that included seizures, spastic diplegia, cognitive impairment, axial and appendicular hypotonia, dysmorphic features, joint hyper-flexibility, attention deficit hyperactivity disorder, skeletal dysplasia in addition to generalized global developmental delay, failure to thrive, speech delay, intellectual disability, and visual impairments. Furthermore, brain Magnetic resonance imaging findings were consistent with variable clinical features and revealed brain atrophy, thinning of corpus callosum, semi-lobar holoprosencephaly, white matter abnormality, diffuse paucity of the myelin within the brain parenchyma, and reduction of white matter arborization in the temporal lobes. Conclusion: In conclusion, these clinical cases highlight the importance of the EMC1 gene in disease phenotype and add up to the expanded EMC1-related phenotype. [JBCGenetics 2021; 4(2.000): 93-99]http://www.ejmanager.com/fulltextpdf.php?mno=22311emc1whole exome sequencingcavipmrbrain mriconsanguinity |
| spellingShingle | Abdul Ali Peer-Zada Osama A. Obaid Manar A. Samman Aqeela AlHashim Hajar AlAsmari Ali M. AlAsmari Neurological and extra-neurological clinical spectrum observed in pediatric patients with EMC1 gene variants identified by whole exome sequencing Journal of Biochemical and Clinical Genetics emc1 whole exome sequencing cavipmr brain mri consanguinity |
| title | Neurological and extra-neurological clinical spectrum observed in pediatric patients with EMC1 gene variants identified by whole exome sequencing |
| title_full | Neurological and extra-neurological clinical spectrum observed in pediatric patients with EMC1 gene variants identified by whole exome sequencing |
| title_fullStr | Neurological and extra-neurological clinical spectrum observed in pediatric patients with EMC1 gene variants identified by whole exome sequencing |
| title_full_unstemmed | Neurological and extra-neurological clinical spectrum observed in pediatric patients with EMC1 gene variants identified by whole exome sequencing |
| title_short | Neurological and extra-neurological clinical spectrum observed in pediatric patients with EMC1 gene variants identified by whole exome sequencing |
| title_sort | neurological and extra neurological clinical spectrum observed in pediatric patients with emc1 gene variants identified by whole exome sequencing |
| topic | emc1 whole exome sequencing cavipmr brain mri consanguinity |
| url | http://www.ejmanager.com/fulltextpdf.php?mno=22311 |
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