ArticleMolecular genetics & genomic medicine2020
An update of pathogenic variants in ASPM, WDR62, CDK5RAP2, STIL, CENPJ, and CEP135 underlying autosomal recessive primary microcephaly in 32 consanguineous families from Pakistan.
Article in Molecular genetics & genomic medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Expanding the genetic spectrum of autosomal recessive microcephaly in Pakistani families.BMC neurology · 2026Article
- Rare genetic causes of primary microcephaly in two Saudi families identified via whole-exome sequencing: Genomic and phenotypic delineation of pathogenicMolecular genetics and metabolism reports · 2026Article
- Clinical and Molecular Characterization of Pakistani Mucopolysaccharidosis Families withGenes · 2026Article
- Studies on intellectual disability identify variants in established genes as well as confirm candidature of new genes.Scientific reports · 2026Article
- Metabolic functions for molecular chaperones and stress proteins in microcephaly.Cellular and molecular life sciences : CMLS · 2025Review
- Genetic variants underlying congenital Zika syndrome and severe microcephaly: a systematic review and meta-analysis.Virusdisease · 2025Article
- Expanding the mutational spectrum of congenital microcephaly in Pakistani families.Frontiers in genetics · 2025Article
- Clinical genomics expands the link between erroneous cell division, primary microcephaly and intellectual disability.Neurogenetics · 2024Article
- Molecular genetics, neuroimaging outcomes, and structural analyses of novel and recurrent variants of WDR62 gene in two consanguineous Pakistani families with autosomal recessive primary microcephaly.Molecular biology reports · 2024Article
- Centrosomes and associated proteins in pathogenesis and treatment of breast cancer.Frontiers in oncology · 2024Review
- Autosomal recessive primary microcephaly type 2 associated with a novelFrontiers in neurology · 2024Article
- Genetic Primary Microcephalies: When Centrosome Dysfunction Dictates Brain and Body Size.Cells · 2023Review
- Review
- The neurological and non-neurological roles of the primary microcephaly-associated protein ASPM.Frontiers in neuroscience · 2023Review
- Autosomal Recessive Primary Microcephaly (MCPH) and Novel Pathogenic Variants inMolecular syndromology · 2022Article
- Identification of Pathogenic Mutations in Primary Microcephaly- (MCPH-) Related Three GenesBioMed research international · 2022Article
- A HomozygousGenes · 2021Article
- Modifier Genes in Microcephaly: A Report onGenes · 2021Article
- Article
- Pathophysiological Significance of WDR62 and JNK Signaling in Human Diseases.Frontiers in cell and developmental biology · 2021Review
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Authors and funding
27 authors at 10 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPrimary microcephaly (MCPH) is a congenital neurodevelopmental disorder manifesting as small brain and intellectual disability. It underlies isolated reduction of the cerebral cortex that is reminiscent of early hominids which makes it suitable model disease to study the hominin-specific volumetric expansion of brain. Mutations in 25 genes have been reported to cause this disorder. Although majority of these genes were discovered in the Pakistani population, still a significant proportion of these families remains uninvestigated.
methodsWe studied a cohort of 32 MCPH families from different regions of Pakistan. For disease gene identification, genome-wide linkage analysis, Sanger sequencing, gene panel, and whole-exome sequencing were performed.
resultsBy employing these techniques individually or in combination, we were able to discern relevant disease-causing DNA variants. Collectively, 15 novel mutations were observed in five different MCPH genes; ASPM (10), WDR62 (1), CDK5RAP2 (1), STIL (2), and CEP135 (1). In addition, 16 known mutations were also verified. We reviewed the literature and documented the published mutations in six MCPH genes. Intriguingly, our cohort also revealed a recurrent mutation, c.7782_7783delGA;p.(Lys2595Serfs*6), of ASPM reported worldwide. Drawing from this collective data, we propose two founder mutations, ASPM:c.9557C>G;p.(Ser3186*) and CENPJ:c.18delC;p.(Ser7Profs*2), in the Pakistani population.
conclusionsWe discovered novel DNA variants, impairing the function of genes indispensable to build a proper functioning brain. Our study expands the mutational spectra of known MCPH genes and also provides supporting evidence to the pathogenicity of previously reported mutations. These novel DNA variants will be helpful for the clinicians and geneticists for establishing reliable diagnostic strategies for MCPH families.
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