TRAIP is necessary for efficient cell cycle progression and mutations in TRAIP therefore limit cellular proliferation, providing a potential mechanism for microcephaly and dwarfism phenotypes.
Autosomal dominant mental retardation-7 (MRD7) is a rare anomaly, characterized by severe intellectual disability, feeding difficulties, behavior abnormalities, and distinctive facial features, including microcephaly, deep-set eyes, large simple ears, and a pointed or bulbous nasal tip.
In the present study, we report 10 unrelated individuals with DYRK1A-associated intellectual disability (ID) who display a recurrent pattern of clinical manifestations including primary or acquired microcephaly, ID ranging from mild to severe, speech delay or absence, seizures, autism, motor delay, deep-set eyes, poor feeding and poor weight gain.
More recently, point mutations in DYRK1A have been shown to be responsible for a recognizable syndrome characterized by microcephaly, developmental delay and intellectual disability (ID) as well as characteristic facial features.
The Down syndrome and microcephaly related gene Mnb/Dyrk1A encodes an evolutionary conserved protein kinase subfamily that plays important roles in neurodevelopment. minibrain (mnb) mutants of Drosophila melanogaster (Dm) exhibit reduced adult brains due to neuronal deficits generated during larval development.
We screened the FOXG1 gene in a cohort of 206 MECP2 and CDKL5 mutation negative patients (136 females and 70 males) with severe encephalopathy and microcephaly.
We propose that a disruption of centrosome integrity and/or spindle organization may play an important role in the development of microcephaly in MCPH2.
Mutations of the CASK gene are associated with X-linked mental retardation with microcephaly and disproportionate brain stem and cerebellar hypoplasia in females.
FOXG1-related disorders are caused by heterozygous mutations in FOXG1 and result in a spectrum of neurodevelopmental phenotypes including postnatal microcephaly, intellectual disability with absent speech, epilepsy, chorea, and corpus callosum abnormalities.
We believe that the FOXG1 gene should be considered in severely mentally retarded patients (no speech-language) with severe acquired microcephaly (-4 to-6 SD) and few clinical features suggestive of Rett syndrome.
WD40-repeat protein 62 (WDR62) was recently identified as a spindle pole protein linked to the neurodevelopmental defect of microcephaly but its roles in mitosis have not been defined.
FOXG1B (forkhead box G1B) is a very intriguing candidate gene since it is known to promote neuronal progenitor proliferation and to suppress premature neurogenesis and its disruption is reported in a patient with postnatal microcephaly, corpus callosum agenesis, seizures, and severe mental retardation.
Loss-of-function mutations of CASK are associated with intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH), especially in females.
Mutations of the calcium/calmodulin-dependent serine protein kinase (CASK) gene have recently been associated with X-linked mental retardation (XLMR) with microcephaly, optic atrophy and brainstem and cerebellar hypoplasia, as well as with an X-linked syndrome having some FG-like features.