A large analphoid invdup(3)(q22.3qter) marker chromosome characterized by array-CGH in a child with malformations, mental retardation, ambiguous genitalia and Blaschko's lines.

We report a new case of mosaic chromosome 3-derived marker chromosome, present in fibroblasts but not in lymphocytes, found in a child with malformations, mental retardation and ambiguous genitalia. Cytogenetic and molecular analysis showed that the supernumerary invdup(3)(q22.3qter) chromosome was negative at FISH with alpha satellite probe. The presence of a functional neocentromere was confirmed by immunofluorescence with antibodies to centromere proteins (CENPs). Definition of the marker breakpoints has been done through array-CGH. The skin of the patient presented dyschromic areas ordered along Blaschko's lines. The invdup(3q) marker chromosome was present only in fibroblasts from the dark skin biopsy, while lymphocytes and fibroblasts from the normal skin showed a normal male karyotype. Expression of the HPS3 gene (MIM: 606118) was more than two times higher in dark skin fibroblasts. Neocentromeres are most often observed on chromosomal arm fragments that have separated from an endogenous centromere, and therefore actually confer mitotic stability to what would have been acentric fragments. To our knowledge, this invdup(3q) analphoid marker is the largest among the several reported so far. Parental origin and possible mode of formation have been defined by DNA polymorphisms studies. The size of the duplicated marker chromosome and its frequency and tissue distribution may be relevant to the severity of the propositus' phenotype.