Hussain et al. identified a homozygous frameshift mutation in CEP135 in a consanguineous family with two siblings affected by primary microcephaly. Reducing CEP135 amounts in cells via RNA interference caused a disorganization of interphase and mitotic spindles, leading to the hypothesis that the CEP135 protein has a role in maintaining the structure and organization of the centrosome and microtubules. CEP135 sequence analysis is only available as part of our MCPH Tier 2 Sequencing Panel. Please see our information sheet for more details.
A homozygous nonsense mutation was identified in CEP63 in a consanguineous family of Pakistani descent with three members with primary microcephaly and, to a lesser extent, proportionate short stature. The CEP63 protein forms a complex with CEP152, and helps to maintain normal centrosome numbers within cells. To date, no deletions or duplications in CEP63 associated with primary microcephaly or Seckel syndrome have been described. CEP63 deletion/duplication analysis is available as an individual test, or as part of one of the following panels: MCPH Tier 2 Deletion/Duplication Panel, Comprehensive Primordial Dwarfism Deletion/Duplication Panel and Seckel Syndrome Deletion/Duplication Panel. Please see our information sheets for more details.
A homozygous nonsense mutation was identified in CEP63 in a consanguineous family of Pakistani descent with three members with primary microcephaly and, to a lesser extent, proportionate short stature. The CEP63 protein forms a complex with CEP152, and helps to maintain normal centrosome numbers within cells. CEP63 sequence analysis is only available as part of one of the following panels: MCPH Tier 2 Sequencing Panel, Comprehensive Primordial Dwarfism Sequencing Panel and Seckel Syndrome Sequencing Panel. Please see our information sheets for more details.
Genin et al. (2012) identified the same CASC5 frameshift mutation in the homozygous state in three separate consanguineous families with primary microcephaly. The CASC5 protein is required for proper microtubule attachment to the chromosome centromere and for spindle-assembly checkpoint activation during mitosis. CASC5 sequence analysis is only available as part of the MCPH Tier 2 Sequencing Panel. Please see our information sheet for more details.
A homozygous missense mutation was identified in MED17 in 5 infants from 4 Jewish families with postnatal progressive microcephaly and severe developmental retardation associated with cerebral and cerebellar atrophy. MED17 deletion/duplication analysis is available either as an individual test or as part of the MCPH Tier 2 Deletion/Duplication panel. Please see our information sheet for more details.
A homozygous missense mutation was identified in MED17 in 5 infants from 4 Jewish families with postnatal progressive microcephaly and severe developmental retardation associated with cerebral and cerebellar atrophy. MED17 sequencing is only available as part of the MCPH Tier 2 Sequencing panel. Please see our information sheet for more details.
Missense and frameshift mutations were identified in ARFGEF2 in two Turkish families with autosomal recessive periventricular heterotopia with microcephaly which is characterized by microcephaly, periventricular heterotopia, ID and recurrent infections. ARFGEF2 deletion/duplication analysis is available as an individual test or as part of the MCPH Tier 2 Deletion/Duplication panel. Please see our information sheet for more details.
Amish lethal microcephaly is characterized by the presence of microcephaly and a tenfold increase in the levels of urinary organic acid 2-ketoglutarate. To date, all affected individuals within the Old Order Amish population (in which the prevalence of this condition in this population is approximately 1 in 500 births) are homozygous for a founder mutation in SLC25A19. The SLC25A19 gene encodes amitochondrial thiamine pyrophosphate carrier. SLC25A19 deletion/duplication analysis is available as an individual test or as part of the MCPH Tier 2 Deletion/Duplication panel. Please see our information sheet for more details.
Patients with microcephaly, cortical malformations, and MR have moderate to severe MR and brain malformations including: callosal abnormalities, polymicrogyria, schizencephaly and subcortical heterotopia. Some of these patients have also been described with seizures. This form of MCPH is caused by mutations in the WDR62 gene. Homozygous missense and frameshift mutations were first reported in seven consanguineous families with primary microcephaly and simplified gyri. Like other MCPH genes, WDR62 encodes a spindle pole protein that is expressed in neuronal precursor cells undergoing mitosis in the proliferative phase of neurogenesis No deletions and/or duplications in WDR62 have been reported in association with autosomal recessive primary microcephaly to date.
Autosomal recessive microcepahly, infantile-onset seizures and developmental delay (MCSZ) is a relatively more severe disorder than autosomal recessive primary microcephaly. Mental retardation is usually severe to profound with variable behavioral problems and seizures are severe and intractable. Mutations in the PNKP gene have been reported in several families with MCSZ. Both homozygous, consanguineous patients and compound heterozygotes were reported. We offer deletion/duplication analysis for PNKP, which is performed by oligonucleotide array-CGH. PNKP deletion/duplication analysis is also available as part of the Microcephaly Tier 2 Deletion/Duplication Panel, or the Early Infantile Epileptic Encephalopathy Panel. Please see our information sheets for more details.
