Test Code: 8944

Autosomal Dominant Mental Retardation 1: MBD5 Gene Sequencing
Test Code: 8944
Turnaround time: 5 weeks

CONDITION DESCRIPTION

Talkowski et al. (2011) mapped the MBD5 gene (2q23.1) to the critical region of the 2q23.1 deletion syndrome. Haploinsufficiency of the MBD5 gene causes Autosomal Dominant Mental Retardation syndrome type 1. Overall, of the features evaluated in individuals with 2q23.1 deletion syndrome and MBD5-specific deletions, approximately 84% were observed in both groups. Features associated with the haploinsufficiency of the MBD5 gene include intellectual disability, developmental delay, motor delay, significant speech impairment, craniofacial manifestations, seizures, constipation, and behavioral problems.

For patients with suspected Autosomal Dominant Mental Retardation syndrome type 1, deletion/duplication analysis is recommended as the first step in mutation identification. For patients in whom mutations are not identified by deletion/duplication analysis, full gene sequencing is appropriate.

References:
• OMIM #611472: MBD5 gene
• OMIM #156200: Autosomal Dominant Mental Retardation Syndrome Type 1
• Talkowski et al. (2011). Am J Hum Genet, 89, 551-563.

GENES
MBD5

INDICATIONS
This test is indicated for:

  • Confirmation of a clinical diagnosis of Autosomal Dominant Mental Retardation syndrome type 1 in whom deletion/duplication analysis was negative.
  • Carrier testing in adults with a family history of Autosomal Dominant Mental Retardation syndrome type 1 in whom deletion/duplication analysis was negative.

METHODOLOGY

PCR amplification of 10 exons contained in the MBD5 gene is performed on the patient’s genomic DNA. Direct sequencing of amplification products is performed in both forward and reverse directions, using automated fluorescence dideoxy sequencing methods. The patient’s gene sequences are then compared to a normal reference sequence. Sequence variations are classified as mutations, benign variants unrelated to disease, or variations of unknown clinical significance. Variants of unknown clinical significance may require further studies of the patient and/or family members. This assay does not interrogate the promoter region, deep intronic regions, or other regulatory elements, and does not detect large deletions.

DETECTION

Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient’s clinical and/or biochemical phenotype.

Analytical Sensitivity: ~99%

SPECIMEN REQUIREMENTS

Submit only 1 of the following specimen types
* Preferred specimen type: Whole Blood

Type: Whole Blood
Specimen Requirements:
In EDTA (purple top) or ACD (yellow top) tube: Infants (2 years): 3-5 ml
Older Children & Adults: 5-10 ml

Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: Saliva
Specimen Requirements:
OrageneTM Saliva Collection kit (available through CEN4GEN) used according to manufacturer instructions.

Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

SPECIAL INSTRUCTIONS
Deletion/duplication analysis is required before sequence analysis. If deletion/duplication analysis is performed by another third party provider, please submit a copy of the deletion/duplication report with the test requisition.

RELATED TESTS

  • Deletion/duplication analysis of the MBD5 gene by CGH array is available and is required before sequence analysis.
  • Custom diagnostic mutation analysis (test code: 6875) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.