SYP-related XLMR: SYP Gene Sequencing

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Condition Description

SYP-related mental retardation is an X-linked condition characterized by mild to moderate intellectual disability.  No additional consistent features have been identified; however, epilepsy was noted in some the individuals with reported SYP mutations.  Female carriers had no manifestation.

Mutations in the SYP gene (Xp11.23-p11.22) cause SYP-related mental retardation.  In 1122 individuals with X-linked intellectual disability, four different mutations were identified in the SYP gene.  SYP encodes an intergral membrane protein of small synaptic vesicles.

For patients with suspected SYP-related X-linked mental retardation, sequence analysis is recommended as the first step in mutation identification. For patients in whom mutations are not identified by full gene sequencing, deletion/duplication analysis is appropriate.

  • OMIM #300653: Mental Retardation, X-Linked, SYP-Related.  
  • OMIM #313475: Synaptophysin. 
  • Tarpey et al. A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. Nature Genetics 2009; 41:535-543.

Genes (1)


This test is indicated for:
  • Confirmation of a clinical diagnosis of SYP-related X-linked mental retardation.
  • Carrier testing in adults with a family history of SYP-related X-linked mental retardation.


PCR amplification of 6 exons contained in the SYP 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.


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 biochemical phenotype.
Analytical Sensitivity: ~99%

Specimen Requirements

When sample fails to meet the acceptable criteria, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (

Submit only 1 of the following specimen types

Preferred specimen type: Whole Blood

Type: Whole Blood

Specimen Requirements:

In EDTA (purple top) tube:
Infants (<2 years): 2-3 ml
Children (>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 EGL) 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

Submit copies of diagnostic biochemical test results with the sample, if appropriate. Contact the laboratory if further information is needed.

Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of EGL Genetics, please submit a copy of the sequencing report with the test requisition.

  • Deletion/duplication analysis of the SYP gene by CGH array is available for those individuals in whom sequence analysis is negative.
  • Custom diagnostic mutation analysis (KM) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.
  • Prenatal testing is available only for known familial mutations to individuals who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.

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