Genetic testing and prenatal diagnosis of X-linked ichthyosis in two pedigrees

Abstract

Objective To analyze genetic testing and prenatal diagnosis of two pedigrees with X-linked ichthyosis. Methods Karyotyping, bacterial artificial chromosomes-on-BeadsTM (BoBs), fluorescence in situ hybridization (FISH) and single nucleotide polymorphism array (SNP-array) were used to detect amniotic fluid and peripheral blood specimens of two pedigrees, one with and one without known family history of ichthyosis. Clinical data was collected and analyzed as well. Results (1) The pedigree without known family history: Prenatal BoBs showed that the XC1 probe of fetusⅣ-12 was from 0.36 to 0.50, suggesting the presence of microdeletion. SNP-array analysis of gravidaⅢ-13 showed a 1.68 Mb copy number deletion at Xp22.31 and four missing Online Mendelian Inheritance in Man (OMIM) genes (HDHD1, STS, VCX and PNPLA4). Fetal SNP-array revealed a deletion of arr[hg19] Xp22.31 (6 455 151-8 135 644)×0, indicating a maternally inherited one. FISH analysis verified the deletion in STS gene in fetus Ⅳ-12, whose karyotype was 46, XY. The gravida's female cousin (Ⅲ-21) and nephew (Ⅳ-14) also had STS gene deletion, which size was the same as that from the gravida and the fetus. Fetus (Ⅳ-12) was delivered at term by cesarean section with normal skin, but an extensive white scales appeared on the abdomen one week after birth and the symptom was aggravated when the weather was dry. The infant was followed up to eight months old and no other clinical symptoms were found. (2) The pedigree with known family history: SNP-array revealed that a 1.2 Mb copy number deletion at Xp22.31 and four missing OMIM genes (HDHD1, STS, VCX and PNPLA4) were detected in pregnant women (Ⅲ-21), proband (Ⅳ-16) and fetus (Ⅳ-17). FISH analysis of the fetus verified the deletion in STS gene. The karyotype of the fetus was 46, XY. FetusⅣ-17 was delivered at term by cesarean section with normal skin, but white scales widely appeared on the abdomen ten days after birth. The infant was followed up to four months old and no other clinical symptoms were found. Conclusion Molecular genetic techniques such as BoBs, FISH and SNP-array are used in combination in this study to provide genetic testing and prenatal diagnosis to two XLI pedigrees, which is helpful for clinical diagnosis and genetic counseling. Key words: Ichthyosis, X-linked; Pedigree; Steryl-sulfatase; Prenatal diagnosis; Genetic testing