Neuronal Migration Disorder Panel

SEQmethod-seq-icon Our Sequence Analysis is based on a proprietary targeted sequencing method OS-Seq™ and offers panels targeted for genes associated with certain phenotypes. A standard way to analyze NGS data for finding the genetic cause for Mendelian disorders. Results in 21 days. DEL/DUPmethod-dup-icon Targeted Del/Dup (CNV) analysis is used to detect bigger disease causing deletions or duplications from the disease-associated genes. Results in 21 days. PLUSmethod-plus-icon Plus Analysis combines Sequence + Del/Dup (CNV) Analysis providing increased diagnostic yield in certain clinical conditions, where the underlying genetic defect may be detectable by either of the analysis methods. Results in 21 days.

Test code: MA2601

The Blueprint Genetics Neuronal Migration Disorder Panel is a 47 gene test for genetic diagnostics of patients with clinical suspicion of neuronal migration disorder.

Neuronal migration disorders (NMDs) are classified based on causative genes as well as on brain MRI and neuropathological findings. More than 25 syndromes resulting from abnormal neuronal migration have been described. Among them are syndromes with several different patterns of inheritance; genetic counseling thus differs greatly between syndromes. This panel enables the genetic basis of neuronal migration disorders to be readily determined. This panel covers the smaller Lissencephaly Panel. Neuronal Migration Disorder Panel is part of the Comprehensive Skeletal / Malformation Syndrome panel.

About Neuronal Migration Disorder

Neuronal migration disorders (NMDs) are a group of birth defects caused by the abnormal migration of neurons in the developing brain and nervous system. During development, neurons must migrate from the areas where they are born to the areas where they will settle into their proper neural circuits. The structural abnormalities found in NMDs include schizencephaly, porencephaly, lissencephaly, agyria, macrogyria, polymicrogyria, pachygyria, microgyria, micropolygyria, neuronal heterotopias, agenesis of the corpus callosum, and agenesis of the cranial nerves. Mutations of many genes are involved in neuronal migration disorders, such as DCX in classical lissencephaly spectrum, TUBA1A in microlissencephaly with agenesis of the corpus callosum, and RELN and VLDLR in lissencephaly with cerebellar hypoplasia. Mutations in ARX cause a variety of phenotypes ranging from hydranencephaly or lissencephaly to early-onset epileptic encephalopathies, including Ohtahara syndrome and infantile spasms or intellectual disability with no brain malformations.

Availability

Results in 3-4 weeks.

Genes in the Neuronal Migration Disorder Panel and their clinical significance
GeneAssociated phenotypesInheritanceClinVarHGMD
ACTB*Baraitser-Winter syndromeAD2726
ACTG1*Deafness, Baraitser-Winter syndromeAD1737
ADGRG1Polymicrogyria, bilateral frontoparietal, Polymicrogyris, bilateral perisylvianAR22
AKT3Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndromeAD821
ARFGEF2Heterotopia, periventricularAR511
ARXLissencephaly, Epileptic encephalopathy, Corpus callosum, agenesis of, with abnormal genitalia, Partington syndrome, Proud syndrome, Hydranencephaly with abnormal genitalia, Mental retardationXL5680
B3GALNT2Muscular dystrophy-dystroglycanopathyAR713
CHD7Isolated gonadotropin-releasing hormone deficiency, CHARGE syndromeAD128746
COL4A1Schizencephaly, Anterior segment dysgenesis with cerebral involvement, Retinal artery tortuosity, Porencephaly, Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, Brain small vessel diseaseAD2788
COL4A2Hemorrhage, intracerebralAD512
COL4A4Alport syndromeAD/AR17170
DCXLissencephaly, Subcortical laminal heterotopiaXL117138
DYNC1H1Spinal muscular atrophy, Charcot-Marie-Tooth disease, Mental retardationAD3453
EMX2SchizencephalyAD46
FHHereditary leiomyomatosis and renal cell cancerAD89161
FKTNMuscular dystrophy-dystroglycanopathy, Dilated cardiomyopathy (DCM), Muscular dystrophy-dystroglycanopathy (limb-girdle)AD/AR2851
FLNAXL86209
GMPPBMuscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), Limb-girdle muscular dystrophy-dystroglycanopathyAR1326
GPSM2Deafness, Chudley-McCullough syndromeAR1011
ISPDMuscular dystrophy-dystroglycanopathyAR2042
KIF1BPGoldberg-Shprintzen megacolon syndromeAR5
KIF7Acrocallosal syndrome, Hydrolethalus syndrome, Al-Gazali-Bakalinova syndrome, Joubert syndromeAR/Digenic1339
L1CAMMental retardation, aphasia, shuffling gait, and adducted thumbs (MASA) syndrome, Hydrocephalus due to congenital stenosis of aqueduct of Sylvius, Spastic, CRASH syndrome, Corpus callosum, partial agenesisXL37286
LAMA2Muscular dystrophy, congenital merosin-deficient, SchizophreniaAD/AR72225
LARGEMuscular dystrophy-dystroglycanopathyAR1522
MED12Ohdo syndrome, Mental retardation, with Marfanoid habitus, FG syndrome, Opitz-Kaveggia syndrome, Lujan-Fryns syndromeXL1719
MEF2CMental retardationAD2566
NDE1Microhydranencephaly, LissencephalyAR1014
NSDHLCongenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD syndrome), CK syndromeXL1528
PAFAH1B1Lissencephaly, Subcortical laminar heterotopiaAD106165
PIK3CA*Cowden syndromeAD3044
POMGNT1Muscular dystrophy-dystroglycanopathyAR5573
POMT1Muscular dystrophy-dystroglycanopathyAR3181
POMT2Muscular dystrophy-dystroglycanopathyAR2848
RAB3GAP1Warburg micro syndromeAR1658
RAB3GAP2Warburg micro syndrome, Martsolf syndromeAR711
RELNLissencephaly, Epilepsy, familial temporal lobeAD/AR1731
SLC12A6Agenesis of the corpus callosum with peripheral neuropathy (Andermann syndrome)AR1217
SRPX2Rolandic epilepsy, mental retardation, and speech dyspraxiaXL13
TMEM5Muscular dystrophy-dystroglycanopathyAR87
TUBA1A*LissencephalyAD3362
TUBA8Polymicrogyria with optic nerve hypoplasiaAR11
TUBB2B*Polymicrogyria, asymmetricAD1229
TUBB3*Fibrosis of extraocular muscles, congenital, Cortical dysplasia, complex, with other brain malformationsAD/AR1823
VLDLRCerebellar ataxia, mental retardation, and dysequilibrium syndromeAR921
WDR62MicrocephalyAR2438
YWHAEDistal 17p13.3 microdeletion syndrome, Endometrial stromal sarcoma, 17p13.3 microduplication syndrome, Miller-Dieker syndromeAD/AR1142
  • * Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.

Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/); HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/). The list of associated (gene specific) phenotypes are generated from CDG (http://research.nhgri.nih.gov/CGD/) or Orphanet (http://www.orpha.net/) databases.

Blueprint Genetics offers a comprehensive neuronal migration disorder panel that covers classical genes associated with neuronal migration disorder. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.

Please see our latest validation report showing sensitivity and specificity for SNPs and indels, sequencing depth, % of the nucleotides reached at least 15x coverage etc. If the Panel is not present in the report, data will be published when the Panel becomes available for ordering. Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. All the Panels available for ordering have sensitivity and specificity higher than > 0.99 to detect single nucleotide polymorphisms and a high sensitivity for indels ranging 1-19 bp. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile. Detection limit for Del/Dup analysis varies through the genome from one to six exon Del/Dups depending on exon size, sequencing coverage and sequence content.

The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (http://www.1000genomes.org), the NHLBI GO Exome Sequencing Project (ESP; http://evs.gs.washington.edu/EVS), the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org), ClinVar database of genotype-phenotype associations (http://www.ncbi.nlm.nih.gov/clinvar) and the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk). The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (http://sift.jcvi.org), Polyphen (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org).

Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.

In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.

Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.

A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.

We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.

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ICD & CPT codes

CPT codes

SEQ81479
DEL/DUP81479


ICD codes

Commonly used ICD-10 codes when ordering the Neuronal Migration Disorder Panel

ICD-10Disease
Q04.3Neuronal migration disorder

Accepted sample types

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 5μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.