Mutations in the PQBP1 gene (Xp11.23) cause X-linked recessive mental retardation that is often syndromic but can be nonsyndromic. PQBP1 mutations have been associated with Renpenning syndrome, Sutherland-Hann syndrome, cerebropalatocardiac (Hamel) syndrome, and Golabi-Ito-Hall syndrome. Common features of X-linked mental retardation caused by PQBP1 mutation seem to be mental retardation, microcephaly, and short stature. Considerable phenotypic variability is observed between families with different mutations and even between families with the same mutation.
In addition to mental retardation, microcephaly, and short stature, other reported features include small testes, ocular colobomas, cardiac malformations, cleft palate, spastic diplegia, and anal anomalies. Facial characteristics include narrow and tall craniofacies with upslanting palpebral fissures, abnormal nasal configuration, cupped ears, and short philtrum. The nose may appear long or bulbous, with overhanging columella.
Historically, Renpenning syndrome has been associated with mental retardation with short stature, moderate microcephaly, but no remarkable facies and no other neurologic abnormalities. Sutherland-Haan syndrome has been associated with mental retardation, short stature, microcephaly, brachycephaly, spastic diplegia, small testes, and possibly intrauterine growth retardation. Cerebropalatocardiac (Hamel) syndrome has been associated with severe mental retardation with congenital heart defects, microcephaly, spasticity, short stature, cleft or highly arched palate, and other craniofacial abnormalities. Golabi-Ito-Hall syndrome has been associated with mental retardation, microcephaly, postnatal growth deficiency, and other anomalies, including atrial septal defect.
For patients with suspected Renpenning syndrome, 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.
Click here for the OMIM summary on this condition.
This test is indicated for:
- Confirmation of a clinical/biochemical diagnosis of Renpenning syndrome
- Carrier testing in adult females with a family history of Renpenning syndrome
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%
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): 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.
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.
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 Emory Genetics Laboratory, please submit a copy of the sequencing report with the test requisition.
- Deletion/duplication analysis of the PQBP1 gene by CGH array is available for those individuals in whom sequence analysis is negative (YQ).
- A CGH array-based test for deletion/duplication analysis of 64 different X-linked intellectual disability genes is available (OL).
- 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 to adult females who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.