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Molecular Genetics Laboratory

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Congenital Variant of Rett Syndrome (FOXG1 Sequencing and Deletion-Duplication Analysis)

  • LIS Mnemonic: MBFOXG1FS


    Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA is acceptable.

    Volume Required

    5ml whole blood or 2 ug of DNA

    Minimum Required



    Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday within 24 hours of collection.


    Whole blood can be refrigerated until shipment.

    Unacceptable conditions

    Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.

    Specimen Handling

    Do not heat, freeze or centrifuge blood before shipment. Refrigerate sample until shipment.

Days Performed

Mon - Fri 9:00am to 4:00pm


4-6 weeks


81404, 81479

Disease Information

Clinical Features:

Classic Rett syndrome is a severe neurodevelopmental disorder that primarily affects females. While classic Rett syndrome is defined on the basis of strict diagnostic criteria, atypical forms of Rett do exist that vary in terms of age of onset (congenital and late regression variants) as well as symptom severity (preserved speech variant). In the congenital variant form, girls are floppy and retarded from the very first months of life. The majority of congenital variants do not bear MECP2 or CDKL5 mutations, with only four cases being reported with MECP2 mutations. Very recently, truncating mutations in the FOXG1 gene have been identified in these patients.

Molecular Genetics:

FOXG1 is located on 14q12. It encodes the forkhead box protein G1, FoxG1, a transcriptional factor with expression restricted to fetal and adult brain and testis. Truncating mutations have been identified in two patients with the congenital variant of Rett syndrome. Large deletions of the 14q12 region encompassing the FOXG1 gene as well as an inversion of the FOXG1 gene have also been described in some patients.

Test Methods:

We offer deletion-duplication testing and DNA sequence analysis of the entire coding region including splice junctions. PCR amplification and sequencing is performed on the coding region. The patient’s gene sequence is then compared to a reference sequence. Sequence variants are classified as mutations, variants of unknown significance or benign variants unrelated to disease. Variants of unknown significance may warrant further studies in the patient and other family members. Large deletions, mutations in promoters, deep intronic regions and other regulatory regions will not be identified with this assay.

Detection Rate:

Mutations in the FOXG1 have been identified in the congenital variant form of RTT syndrome. Overall, mutations are present in about 4% of RTT patients that are MECP2 and CDKL5 negative. The analytical sensitivity of this assay is 99%.

Related Tests:

Atypical Rett syndrome/Infantile Spasms Panel: ARX/MECP2/CDKL5 Sequencing + MECP2 Deletion/Duplication Analysis Rett syndrome: MECP2 Gene Sequencing Rett syndrome: MECP2 Gene Deletion/Duplication Analysis Infantile Spasms: ARX Sequencing Known mutation analysis is available to family members for mutations previously identified by sequence analysis. Prenatal Testing is available to adult females who are confirmed carriers of mutations. Please contact the laboratory director to discuss appropriate testing prior to collecting a prenatal specimen.


Test results with interpretation will be mailed and/or faxed to the referring physician or laboratory following completion of the test. Additional reports will be provided as requested.


The clinical utility of such testing is to support a clinical diagnosis of the disease, facilitate genetic counseling, assess the risk to other first degree relatives and to facilitate testing of at - risk family members.

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