FOCAL DERMAL HYPOPLASIA
PORCN Sequencing Analysis
DNA ANALYSIS

Focal dermal hypoplasia (FDH; also known as Goltz syndrome; OMIM #305600) is a condition with distinctive skin abnormalities and associated findings in other organ systems such as eyes, nails, hair, skeleton, renal, and central nervous system. Approximately 15% of affected individuals have mental retardation. The characteristic skin lesions are patchy areas of dermal hypoplasia with deposition of subcutaneous fat into the dermis. This disorder occurs predominantly in females, although transmission from mildly affected fathers to severely affected daughters has been reported. Recently, mutations in the X-linked gene, PORCN, have been found in patients with FDH. PORCN is the human homolog of D. melanogaster Porcupine which is a membrane-bound endoplasmic reticulum protein required for the secretion of Wnt proteins. Heterozygous sequence changes in the PORCN gene were found in approximately 70-80% of females with confirmed or suspected FDH, while mosaic mutations with overlapping normal and mutant sequences were found in male FDH cases. Somatic mosaicism is postulated to be the mechanism underlying the finding of mildly affected males, while X-chromosome inactivation is thought to be responsible for the phenotypic variability in females. DNA sequencing analysis of the PORCN gene is available at the Baylor Medical Genetics Laboratories.

Reasons for Referral:

Confirmation of clinical diagnosis of Focal Dermal Hypoplasia in both females and males.
Testing of at-risk family members (known familial mutation)
Prenatal diagnosis (known familial mutation only)

Testing Methodology:

Full Sequencing: PCR amplification of 10 exons contained in the PORCN gene coding region will be performed on patient genomic DNA. Direct sequencing of amplification products is performed in both the forward and reverse directions using automated fluorescence dideoxy sequencing methods.

Sensitivity:

Analytical: ~99%
Clinical: 70%

Specimen Requirements:

Blood for DNA: EDTA (purple-top) tubes: Adults: 14 cc; Child/Infant: 6 cc
Requisition form must accompany specimen. Prior to any genetic testing, we recommend genetic counseling and request that the subject, or their legal guardian, sign our consent form and submit it with the sample. To receive our forms and information about prenatal testing, please contact our laboratory.

Turnaround Time:

4 weeks

CPT Codes and Prices:

Index: 83891, 83898X11, 83894, 83904x22, 83909x22, 83912
Known Familial Mutation: 83904x2, 83912, 83909x2, 83898, 83891, 83894
Prenatal (Known Familial Mutation Only): 83891x2, 83898x4, 83894x2, 83904x4, 83909x6, 83900x2, 83901x30, 83912x2

References:

1. Xiaoling Wang, V Reid Sutton, J Omar Peraza-Llanes et al. (2007). Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia. Nature Genetics 39: 836-839.
2. Karl-Heinz Grzeschik, Dorothea Bornholdt, Frank Oeffner et al. (2007). Deficiency of PORCN, a regulator of Wnt signaling, is associated with focal dermal hypoplasia. Nature Genetics 39: 833-835.

Shipping Information

Forms:

>> Gene Sequencing Requisition
>> Prenatal Requisition

Test Codes

Index: 6345
Known Familial Mutation: 6346
Prenatal (Known Familial Mutation Only): 6347