GTR Home > Tests > Microcephaly Sequencing Panel

Overview

Test name

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Microcephaly Sequencing Panel

Purpose of the test

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This is a clinical test intended for Help: Diagnosis, Monitoring, Mutation Confirmation, Pre-symptomatic, Risk Assessment, Screening

Condition

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50 conditions tested. Click Indication tab for more information.

Methodology

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Molecular Genetics
CSequence analysis of the entire coding region
Next-Generation (NGS)/Massively parallel sequencing (MPS)

Summary of what tested

53 genes and variants. Click Methodology tab for more information.

Genes and variants

Clinical validity

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Missense and frameshift mutations were identified in two Turkish families with autosomal recessive periventricular heterotopia with microcephaly [OMIM#608097] which is characterized by microcephaly, periventricular heterotopia, intellectual disability and recurrent infections. A homozygous mutation in ATR was been identified in two consanguineous Pakistani families with Seckel syndrome [OMIM#210600]. Seckel syndrome is characterized by severe proportionally short stature with severe microcephaly, a ‘bird like’ profile including a beak-like protusion of the nose, narrow face, receding lower jaw and micrognathia, and intellectual disability. Mutations in ATRX are associated with a wide and clinically heterogeneous spectrum of X-linked mental retardation syndromes. Clinical features may include intellectual disability, hypotonia, microcephaly, genital abnormalities, short stature and seizures. Affected individuals may have microcytic hypochromic anemia characteristic of alpha-thalassemia, however many do not. Carrier females are typically not affected. X-linked mental retardation and microcephaly with pontine and cerebellar hypoplasia (MIC-PHC) [OMIM #300749] is associated with de novo CASK mutations, and is characterized by severe or profound intellectual disability, microcephaly, and disproportionate pontine and cerebellar hypoplasia in females. Mutations associated with MIC-PHC are believed to be lethal in males, however milder familial mutations may also be observed, which can cause intellectual disability in males. A homozygous nonsense mutation was identified in CEP63 in a consanguineous family of Pakistani descent with three members with primary microcephaly and proportionate short stature, clinically consistent with mild Seckel syndrome [OMIM#614728]. A homozygous missense mutation was identified in 5 infants from 4 Jewish families with postnatal progressive microcephaly and severe developmental retardation associated with cerebral and cerebellar atrophy. Mutations in NDE1 have been reported in childr

Citations
  • Identification of microcephalin, a protein implicated in determining the size of the human brain. - PubMed ID: 12046007
  • ASPM is a major determinant of cerebral cortical size. - PubMed ID: 12355089
  • A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome. - PubMed ID: 12640452
  • Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex. - PubMed ID: 14647276
  • Mutations in microcephalin cause aberrant regulation of chromosome condensation. - PubMed ID: 15199523
  • Mutations of the catalytic subunit of RAB3GAP cause Warburg Micro syndrome. - PubMed ID: 15696165
  • A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size. - PubMed ID: 15793586
  • Autosomal recessive primary microcephaly (MCPH): a review of clinical, molecular, and evolutionary findings. - PubMed ID: 15806441
  • The first missense alteration in the MCPH1 gene causes autosomal recessive microcephaly with an extremely mild cellular and clinical phenotype. - PubMed ID: 16211557
  • A novel deletion mutation in CENPJ gene in a Pakistani family with autosomal recessive primary microcephaly. - PubMed ID: 16900296
  • Previously described sequence variant in CDK5RAP2 gene in a Pakistani family with autosomal recessive primary microcephaly. - PubMed ID: 17764569
  • Mutations in the pericentrin (PCNT) gene cause primordial dwarfism. - PubMed ID: 18174396
  • SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and ataxia, a phenotype mimicking Angelman syndrome. - PubMed ID: 18342287
  • The molecular landscape of ASPM mutations in primary microcephaly. - PubMed ID: 19028728
  • Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum. - PubMed ID: 19165920
  • Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins syndrome. - PubMed ID: 19235238
  • The expanding phenotype of GLUT1-deficiency syndrome. - PubMed ID: 19304421
  • Mutations in PNKP cause microcephaly, seizures and defects in DNA repair. - PubMed ID: 20118933
  • New RAB3GAP1 mutations in patients with Warburg Micro Syndrome from different ethnic backgrounds and a possible founder effect in the Danish. - PubMed ID: 20512159
  • Mutations in WDR62, encoding a centrosome-associated protein, cause microcephaly with simplified gyri and abnormal cortical architecture. - PubMed ID: 20890278
  • Infantile cerebral and cerebellar atrophy is associated with a mutation in the MED17 subunit of the transcription preinitiation mediator complex. - PubMed ID: 20950787
  • Loss-of-function mutations in RAB18 cause Warburg micro syndrome. - PubMed ID: 21473985
  • The essential role of centrosomal NDE1 in human cerebral cortex neurogenesis. - PubMed ID: 21529752
  • A primary microcephaly protein complex forms a ring around parental centrioles. - PubMed ID: 21983783
  • CtIP Mutations Cause Seckel and Jawad Syndromes. - PubMed ID: 21998596
  • A truncating mutation of CEP135 causes primary microcephaly and disturbed centrosomal function. - PubMed ID: 22521416
  • Kinetochore KMN network gene CASC5 mutated in primary microcephaly. - PubMed ID: 22983954
  • Epilepsy in Rett syndrome, and CDKL5- and FOXG1-gene-related encephalopathies. - PubMed ID: 22998673
  • Microcephaly gene links trithorax and REST/NRSF to control neural stem cell proliferation and differentiation. - PubMed ID: 23178126
  • Mutations in STAMBP, encoding a deubiquitinating enzyme, cause microcephaly-capillary malformation syndrome. - PubMed ID: 23542699
  • CDKL5 and ARX mutations in males with early-onset epilepsy. - PubMed ID: 23583054
  • Adam M, Bean L, Miller V. Mowat-Wilson Syndrome. In: Pagon R, Bird T, Dolan C, eds. GeneReviews [Internet]. Seattle: University of Washington, 2007.
  • Christodoulou J, Ho G. MECP2-Related Disorders. In: Pagon R, Bird T, Dolan C, eds. GeneReviews [Internet]. Seattle: University of Washington, 2001.
  • Dagli A, Williams C. Angelman Syndrome. In: Pagon R, Bird T, Dolan C, eds. GeneReviews [Internet]. Seattle: University of Washington, 1998.
  • Faivre L, Cormier-Daire V. Seckel Syndrome. Orphanet encyclopedia, 2005.
  • Lindhurst M, Biesecker L. Amish Lethal Microcephaly. In: Pagon R, Bird T, Dolan C, eds. GeneReviews [Internet]. Seattle: University of Washington, 2011.
  • S P. Autosomal Recessive Microcephaly. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2013., 2009 Sep 1.
  • Stevenson R. Alpha-Thalassemia X-Linked Intellectual Disability Syndrome. In: Pagon R, Bird T, Dolan C, eds. GeneReviews [Internet]. Seattle: University of Washington, 2000.

Clinical utility

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Establish or confirm diagnosis

Citations
  • Identification of microcephalin, a protein implicated in determining the size of the human brain. - PubMed ID: 12046007
  • ASPM is a major determinant of cerebral cortical size. - PubMed ID: 12355089
  • A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome. - PubMed ID: 12640452
  • Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex. - PubMed ID: 14647276
  • Mutations in microcephalin cause aberrant regulation of chromosome condensation. - PubMed ID: 15199523
  • Mutations of the catalytic subunit of RAB3GAP cause Warburg Micro syndrome. - PubMed ID: 15696165
  • A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size. - PubMed ID: 15793586
  • Autosomal recessive primary microcephaly (MCPH): a review of clinical, molecular, and evolutionary findings. - PubMed ID: 15806441
  • The first missense alteration in the MCPH1 gene causes autosomal recessive microcephaly with an extremely mild cellular and clinical phenotype. - PubMed ID: 16211557
  • A novel deletion mutation in CENPJ gene in a Pakistani family with autosomal recessive primary microcephaly. - PubMed ID: 16900296
  • Previously described sequence variant in CDK5RAP2 gene in a Pakistani family with autosomal recessive primary microcephaly. - PubMed ID: 17764569
  • Mutations in the pericentrin (PCNT) gene cause primordial dwarfism. - PubMed ID: 18174396
  • SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and ataxia, a phenotype mimicking Angelman syndrome. - PubMed ID: 18342287
  • The molecular landscape of ASPM mutations in primary microcephaly. - PubMed ID: 19028728
  • Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum. - PubMed ID: 19165920
  • Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins syndrome. - PubMed ID: 19235238
  • The expanding phenotype of GLUT1-deficiency syndrome. - PubMed ID: 19304421
  • Mutations in PNKP cause microcephaly, seizures and defects in DNA repair. - PubMed ID: 20118933
  • New RAB3GAP1 mutations in patients with Warburg Micro Syndrome from different ethnic backgrounds and a possible founder effect in the Danish. - PubMed ID: 20512159
  • Mutations in WDR62, encoding a centrosome-associated protein, cause microcephaly with simplified gyri and abnormal cortical architecture. - PubMed ID: 20890278
  • Infantile cerebral and cerebellar atrophy is associated with a mutation in the MED17 subunit of the transcription preinitiation mediator complex. - PubMed ID: 20950787
  • Loss-of-function mutations in RAB18 cause Warburg micro syndrome. - PubMed ID: 21473985
  • The essential role of centrosomal NDE1 in human cerebral cortex neurogenesis. - PubMed ID: 21529752
  • A primary microcephaly protein complex forms a ring around parental centrioles. - PubMed ID: 21983783
  • CtIP Mutations Cause Seckel and Jawad Syndromes. - PubMed ID: 21998596
  • A truncating mutation of CEP135 causes primary microcephaly and disturbed centrosomal function. - PubMed ID: 22521416
  • Kinetochore KMN network gene CASC5 mutated in primary microcephaly. - PubMed ID: 22983954
  • Epilepsy in Rett syndrome, and CDKL5- and FOXG1-gene-related encephalopathies. - PubMed ID: 22998673
  • Microcephaly gene links trithorax and REST/NRSF to control neural stem cell proliferation and differentiation. - PubMed ID: 23178126
  • Mutations in STAMBP, encoding a deubiquitinating enzyme, cause microcephaly-capillary malformation syndrome. - PubMed ID: 23542699
  • CDKL5 and ARX mutations in males with early-onset epilepsy. - PubMed ID: 23583054
  • Adam M, Bean L, Miller V. Mowat-Wilson Syndrome. In: Pagon R, Bird T, Dolan C, eds. GeneReviews [Internet]. Seattle: University of Washington, 2007.
  • Christodoulou J, Ho G. MECP2-Related Disorders. In: Pagon R, Bird T, Dolan C, eds. GeneReviews [Internet]. Seattle: University of Washington, 2001.
  • Dagli A, Williams C. Angelman Syndrome. In: Pagon R, Bird T, Dolan C, eds. GeneReviews [Internet]. Seattle: University of Washington, 1998.
  • Faivre L, Cormier-Daire V. Seckel Syndrome. Orphanet encyclopedia, 2005.
  • Lindhurst M, Biesecker L. Amish Lethal Microcephaly. In: Pagon R, Bird T, Dolan C, eds. GeneReviews [Internet]. Seattle: University of Washington, 2011.
  • S P. Autosomal Recessive Microcephaly. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2013., 2009 Sep 1.
  • Stevenson R. Alpha-Thalassemia X-Linked Intellectual Disability Syndrome. In: Pagon R, Bird T, Dolan C, eds. GeneReviews [Internet]. Seattle: University of Washington, 2000.

How to order

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All samples should be shipped via overnight delivery at room temperature. No weekend or holiday deliveries. Label each specimen with the patient’s name, date of birth and date sample collected. Send specimens with complete requisition and consent form, otherwise, specimen processing may be delayed.
Order URL Help: http://dnatesting.uchicago.edu/submitting-sample

Test services

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  • Clinical Testing/Confirmation of Mutations Identified Previously
  • Confirmation of research findings
  • Custom Prenatal Testing
  • Custom mutation-specific/Carrier testing

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