title: Trisomic rescue causing reduction to homozygosity for a novel ABCA12 mutation in harlequin ichthyosis.
abstract: Harlequin ichthyosis (HI) is the most severe and often lethal form of congenital ichthyosis, characterized by abnormal desquamation and extreme skin thickening and hardening over the entire body. It is caused by recessive loss-of-function mutations in the ABCA12 gene located on chromosome 2q34. Here, we report a sporadic HI patient born prematurely due to severe growth delay and oligohydramnios. The diagnosis was confirmed by ABCA12 molecular analysis, which disclosed the novel homozygous mutation p.R287X. Microsatellite analysis and parental segregation study showed that the disease resulted from complete paternal isodisomy. In addition, chorionic villus karyotyping revealed a non-mosaic chromosome 2 trisomy, while postnatal peripheral blood karyotype resulted normal female. Thus, these findings indicate that trisomic rescue is one step of the mutational cascade leading to reduction to homozygosity for the ABCA12 mutation in the embryo. Our case is the first reported HI patient in whom the disease is due to uniparental isodisomy.
authors: Laboratory of Molecular and Cell Biology, Istituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy. d.castiglia@idi.it
authors: D
authors: D
authors: Castiglia
authors: M
authors: M
authors: Castori
authors: E
authors: E
authors: Pisaneschi
authors: M
authors: M
authors: Sommi
authors: C
authors: C
authors: Covaciu
authors: G
authors: G
authors: Zambruno
authors: J
authors: J
authors: Fischer
authors: C
authors: C
authors: Magnani
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D017490:Ichthyosis, Lamellar / Q000235:genetics*; D007621:Karyotyping; D018895:Microsatellite Repeats / Q000235:genetics; D014314:Trisomy / Q000235:genetics*; D024182:Uniparental Disomy / Q000235:genetics*
chemical_list: C473801:ABCA12 protein, human; D018528:ATP-Binding Cassette Transporters