A locus for familial skewed X chromosome inactivation maps to chromosome Xq25 in a family with a female manifesting Lowe syndrome.
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.
Cau
Milena
M
Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, via Jenner s/n, 09134, Cagliari, Italy.
Addis
Maria
M
Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, via Jenner s/n, 09134, Cagliari, Italy.
Congiu
Rita
R
Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, via Jenner s/n, 09134, Cagliari, Italy.
Meloni
Cristiana
C
Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, via Jenner s/n, 09134, Cagliari, Italy.
Cao
Antonio
A
Istituto di Neurogenetica e Neurofarmacologia, CNR, Selargius (CA), Italy.
Santaniello
Simona
S
Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, via Jenner s/n, 09134, Cagliari, Italy.
Loi
Mario
M
Servizio di Neuropsichiatria. Azienda Ospedaliera G. Brotzu, Cagliari, Italy.
Emma
Francesco
F
Department of Nephrology and dialysis, Bambino Gesù, Children's Research Hospital, Rome, Italy.
Zuffardi
Orsetta
O
Genetica Medica Università di Pavia, Pavia, Italy.|IRCSS Policlinico San Matteo, Pavia, Italy.
Ciccone
Roberto
R
Genetica Medica Università di Pavia, Pavia, Italy.
Sole
Gabriella
G
Istituto di Neurogenetica e Neurofarmacologia, CNR, Selargius (CA), Italy.
Melis
Maria Antonietta
MA
Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, via Jenner s/n, 09134, Cagliari, Italy. amelis@mcweb.unica.it.
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
D005819:Genetic Markers; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA; D010744:Phosphoric Monoester Hydrolases; C075695:OCRL protein, human