TY - JOUR
T1 - Investigating the effects of a single ASPM variant (c.8508_8509) on brain architecture among siblings in a consanguineous Pakistani family
AU - Aslam, Komal
AU - Saeed, Aysha
AU - Jamil, Iffat
AU - Saeed, Hafiza Iqra
AU - Khan, Ramisha
AU - Hassan, Samina
AU - Rafiq, Shereen
AU - Asif, Maria
AU - Makhdoom, Ehtisham Ul Haq
AU - Bashir, Rasheeda
AU - Hussain, Muhammad Sajid
AU - Baig, Shahid Mahmood
AU - Anjum, Iram
N1 - Publisher Copyright:
© 2024, The Author(s), under exclusive licence to Springer Nature B.V.
PY - 2024/12
Y1 - 2024/12
N2 - Background: Autosomal Recessive Primary Microcephaly (MCPH) is a rare, neurodevelopmental disorder associated with mild to severe mental retardation. It is characterized by reduced cerebral cortex that ultimately leads to reduction in skull size less than − 3 S.D below the mean for normal individuals having same age and sex. Till date, 30 known loci have been reported for MCPH. Methods: In the present study, Sanger sequencing was performed followed by linkage analysis to validate the mutation in ASPM gene of the consanguineous Pakistani clans. Bioinformatics tools were also used to confirm the pathogenicity of the diseased variant in the gene. MRI scan was used to compare the brain structure of both the affected individuals (Aslam et al. in Kinnaird’s 2nd International Conference on Science, Technology and Innovation, Lahore, 2023). Results: Our study described a consanguineous family with two patients with a known ASPM (MCPH5) variant c.8508_8509delGA causing a frameshift mutation in exon 18 which located in calmodulin-binding IQ domain of the ASPM protein. The salient feature of this study is that a single variant led to significantly distinct changes in the architecture of brain of both siblings which is further confirmed by MRI results. The computation analysis showed that the change in the conservation of this residue cause this variant highly pathogenic. Carrier screening and genetic counselling were also remarkable features of this study (Aslam et al. in Kinnaird’s 2nd International Conference on Science, Technology and Innovation, Lahore, 2023). Conclusion: This study explores the extraordinary influence of a single ASPM variant on divergent brain structure in consanguineous siblings and enable us to reduce the incidence of further microcephalic cases in this Pakistani family (Aslam et al. in Kinnaird’s 2nd International Conference on Science, Technology and Innovation, Lahore, 2023).
AB - Background: Autosomal Recessive Primary Microcephaly (MCPH) is a rare, neurodevelopmental disorder associated with mild to severe mental retardation. It is characterized by reduced cerebral cortex that ultimately leads to reduction in skull size less than − 3 S.D below the mean for normal individuals having same age and sex. Till date, 30 known loci have been reported for MCPH. Methods: In the present study, Sanger sequencing was performed followed by linkage analysis to validate the mutation in ASPM gene of the consanguineous Pakistani clans. Bioinformatics tools were also used to confirm the pathogenicity of the diseased variant in the gene. MRI scan was used to compare the brain structure of both the affected individuals (Aslam et al. in Kinnaird’s 2nd International Conference on Science, Technology and Innovation, Lahore, 2023). Results: Our study described a consanguineous family with two patients with a known ASPM (MCPH5) variant c.8508_8509delGA causing a frameshift mutation in exon 18 which located in calmodulin-binding IQ domain of the ASPM protein. The salient feature of this study is that a single variant led to significantly distinct changes in the architecture of brain of both siblings which is further confirmed by MRI results. The computation analysis showed that the change in the conservation of this residue cause this variant highly pathogenic. Carrier screening and genetic counselling were also remarkable features of this study (Aslam et al. in Kinnaird’s 2nd International Conference on Science, Technology and Innovation, Lahore, 2023). Conclusion: This study explores the extraordinary influence of a single ASPM variant on divergent brain structure in consanguineous siblings and enable us to reduce the incidence of further microcephalic cases in this Pakistani family (Aslam et al. in Kinnaird’s 2nd International Conference on Science, Technology and Innovation, Lahore, 2023).
KW - ASPM
KW - Carrier screening
KW - Consanguineous marriages
KW - Genetic counselling
KW - Mental retardation
KW - Primary microcephaly
UR - http://www.scopus.com/inward/record.url?scp=85182475563&partnerID=8YFLogxK
U2 - 10.1007/s11033-023-09161-2
DO - 10.1007/s11033-023-09161-2
M3 - Article
C2 - 38224417
AN - SCOPUS:85182475563
SN - 0301-4851
VL - 51
JO - Molecular Biology Reports
JF - Molecular Biology Reports
IS - 1
M1 - 104
ER -