TY - JOUR
T1 - A locus for familial skewed X chromosome inactivation maps to chromosome Xq25 in a family with a female manifesting Lowe syndrome
AU - Cau, Milena
AU - Addis, Maria
AU - Congiu, Rita
AU - Meloni, Cristiana
AU - Cao, Antonio
AU - Santaniello, Simona
AU - Loi, Mario
AU - Emma, Francesco
AU - Zuffardi, Orsetta
AU - Ciccone, Roberto
AU - Sole, Gabriella
AU - Melis, Maria Antonietta
PY - 2006/11
Y1 - 2006/11
N2 - 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.
AB - 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.
KW - Family study
KW - Lowe syndrome
KW - Skewed X inactivation
KW - X chromosome inactivation
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U2 - 10.1007/s10038-006-0049-6
DO - 10.1007/s10038-006-0049-6
M3 - Article
C2 - 16955230
AN - SCOPUS:33751268123
VL - 51
SP - 1030
EP - 1036
JO - Journal of Human Genetics
JF - Journal of Human Genetics
SN - 1434-5161
IS - 11
ER -