CEP152 – Autosomal Recessive Primary Microcephaly

Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder defined by reduced head circumference at birth and non-progressive intellectual disability, reflecting a diminished but architecturally normal cerebral cortex. CEP152, a centrosomal scaffold essential for centriole duplication and bipolar spindle assembly, was identified as the gene at the MCPH5 locus among twelve mapped MCPH genes through homozygosity mapping and exome sequencing in multiple consanguineous cohorts (PMID:25951892). Early clinical studies across diverse populations confirmed CEP152’s involvement in MCPH alongside other centrosomal genes (PMID:21668957).

Targeted analysis in 57 consanguineous Pakistani MCPH families revealed biallelic CEP152 variants in two unrelated pedigrees, each segregating with classical MCPH phenotypes under an autosomal recessive model, consistent with loss-of-function pathogenicity (PMID:22775483). Functional insights indicate that CEP152 deficiency impairs centrosome biogenesis, spindle orientation in neural progenitors, and subsequent neuron production, directly linking molecular defect to reduced brain size. No studies have disputed this association. Overall, CEP152–related MCPH currently meets a Limited clinical validity classification, supporting its inclusion in molecular diagnostic panels and genetic counselling for affected families.

References

• BMC medical genomics • 2015 • Molecular genetics of human primary microcephaly: an overview. PMID:25951892
• Orphanet journal of rare diseases • 2011 • Autosomal Recessive Primary Microcephaly (MCPH): clinical manifestations, genetic heterogeneity and mutation continuum. PMID:21668957
• Clinical genetics • 2013 • Genetic heterogeneity in Pakistani microcephaly families. PMID:22775483

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