title: A locus for familial skewed X chromosome inactivation maps to chromosome Xq25 in a family with a female manifesting Lowe syndrome.
abstract: In mammals, X-linked gene products can be dosage compensated between males and females by inactivation of one of the two X chromosomes in the developing female embryos. X inactivation choice is usually random in embryo mammals, but several mechanisms can influence the choice determining skewed X inactivation. As a consequence, females heterozygous for X-linked recessive disease can manifest the full phenotype. Herein, we report a family with extremely skewed X inactivation that produced the full phenotype of Lowe syndrome, a recessive X-linked disease, in a female. The X chromosome inactivation studies detected an extremely skewed inactivation pattern with a ratio of 100:0 in the propositus as well as in five out of seven unaffected female relatives in four generations. The OCRL1 "de novo" mutation resides in the active paternally inherited X chromosome. X chromosome haplotype analysis suggests the presence of a locus for the familial skewed X inactivation in chromosome Xq25 most likely controlling X chromosome choice in X inactivation or cell proliferation. The description of this case adds Lowe syndrome to the list of X-linked disorders which may manifest the full phenotype in females because of the skewed X inactivation.
authors.affiliation: Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, via Jenner s/n, 09134, Cagliari, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Cau
authors.affiliation: Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, via Jenner s/n, 09134, Cagliari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Addis
authors.affiliation: Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, via Jenner s/n, 09134, Cagliari, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Congiu
authors.affiliation: Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, via Jenner s/n, 09134, Cagliari, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Meloni
authors.affiliation: Istituto di Neurogenetica e Neurofarmacologia, CNR, Selargius (CA), Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cao
authors.affiliation: Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, via Jenner s/n, 09134, Cagliari, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Santaniello
authors.affiliation: Servizio di Neuropsichiatria. Azienda Ospedaliera G. Brotzu, Cagliari, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Loi
authors.affiliation: Department of Nephrology and dialysis, Bambino Gesù, Children's Research Hospital, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Emma
authors.affiliation: Genetica Medica Università di Pavia, Pavia, Italy.|IRCSS Policlinico San Matteo, Pavia, Italy.
authors.forename: Orsetta
authors.initials: O
authors.lastname: Zuffardi
authors.affiliation: Genetica Medica Università di Pavia, Pavia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ciccone
authors.affiliation: Istituto di Neurogenetica e Neurofarmacologia, CNR, Selargius (CA), Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Sole
authors.affiliation: Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, via Jenner s/n, 09134, Cagliari, Italy. amelis@mcweb.unica.it.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Melis
mesh_terms: D041321:Chromosomes, Human, X; D003582:Cytogenetics; D005192:Family Health; D005260:Female; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D007621:Karyotyping; D008297:Male; D009800:Oculocerebrorenal Syndrome; D010375:Pedigree; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D017422:Sequence Analysis, DNA; D049951:X Chromosome Inactivation
chemical_list: D005819:Genetic Markers; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA; D010744:Phosphoric Monoester Hydrolases; C075695:OCRL protein, human