Prenatal Diagnosis of Xq26.1-q26.3 Duplication in Two Fetuses of a Woman with Gonadal Mosaicism

Abstract

We report prenatal diagnosis of two affected males with an Xq26.1-q26.3 duplication from a mother with gonadal mosaicism. The first affected pregnancy was referred by ultrasound observed intrauterine growth retardation and abnormal cerebellar anatomy. Chromosome analysis on cultured amniocytes found a normal male karyotype but array comparative genomic hybridization (aCGH) detected a 4.808 Mb duplication at Xq26.1-q26.3. The proband was born at 35 weeks gestation. At age of three years, he presented with growth retardation, scoliosis, short stature and micropenis. Follow up aCGH analysis on a peripheral blood sample from the mother found a normal result. The second pregnancy was referred due to advanced maternal age and previous history of an affected child. Prenatal chromosome analysis on chorionic villus sampling found a normal male karyotype and aCGH detected the same Xq26.1-q26.3 duplication. The recurrence of this duplication indicated the presence of gonadal mosaicism in the mother. Of the 28 refseq genes within the duplicated region, mutations in genes AIFM1, IGSF1, FRMD7, GPC3, PHF6 and HPRT1 are known to be associated with syndromic phenotypes in the Online Mendelian Inheritance in Man (OMIM). It was reported that deletions of the GPC3 gene in males causes Simpson-Golabi-Behmel syndrome featuring an overgrowth phenotype and a deletion involving IGSF1 results in gonadal enlargement. The duplication of these two genes in our cases is associated with growth retardation and micropenis.