Search results for " X-inactivation"
showing 6 items of 6 documents
Xq28 duplication includingMECP2in six unreported affected females: what can we learn for diagnosis and genetic counselling?
2017
Duplication of the Xq28 region, involving MECP2 (dupMECP2), has been primarily described in males with severe developmental delay, spasticity, epilepsy, stereotyped movements and recurrent infections. Carrier mothers are usually asymptomatic with an extremely skewed X chromosome inactivation (XCI) pattern. We report a series of six novel symptomatic females carrying a de novo interstitial dupMECP2, and review the 14 symptomatic females reported to date, with the aim to further delineate their phenotype and give clues for genetic counselling. One patient was adopted and among the other 19 patients, seven (37%) had inherited their duplication from their mother, including three mildly (XCI: 70…
PORCN mutations in focal dermal hypoplasia: coping with lethality.
2009
Contains fulltext : 81709.pdf (Publisher’s version ) (Closed access) The X-linked dominant trait focal dermal hypoplasia (FDH, Goltz syndrome) is a developmental defect with focal distribution of affected tissues due to a block of Wnt signal transmission from cells carrying a detrimental PORCN mutation on an active X-chromosome. Molecular characterization of 24 unrelated patients from different ethnic backgrounds revealed 23 different mutations of the PORCN gene in Xp11.23. Three were microdeletions eliminating PORCN and encompassing neighboring genes such as EBP, the gene associated with Conradi-Hunermann-Happle syndrome (CDPX2). 12/24 patients carried nonsense mutations resulting in loss …
PORCNmutations in focal dermal hypoplasia: coping with lethality
2009
The X-linked dominant trait focal dermal hypoplasia (FDH, Goltz syndrome) is a developmental defect with focal distribution of affected tissues due to a block of Wnt signal transmission from cells carrying a detrimental PORCN mutation on an active X-chromosome. Molecular characterization of 24 unrelated patients from different ethnic backgrounds revealed 23 different mutations of the PORCN gene in Xp11.23. Three were microdeletions eliminating PORCN and encompassing neighboring genes such as EBP, the gene associated with Conradi-Hunermann-Happle syndrome (CDPX2). 12/24 patients carried nonsense mutations resulting in loss of function. In one case a canonical splice acceptor site was mutated…
Intestinal malrotation in a female newborn affected by Osteopathia Striata with Cranial Sclerosis due to a de novo heterozygous nonsense mutation of …
2022
Abstract Background Osteopathia Striata with Cranial Sclerosis (OS-CS), also known as Horan-Beighton Syndrome, is a rare genetic disease; about 90 cases have been reported to date. It is associated with mutations (heterozygous for female subjects and hemizygous for males) of the AMER1 gene, located at Xq11.2, and shows an X-linked pattern of transmission. Typical clinical manifestations include macrocephaly, characteristic facial features (frontal bossing, epicanthal folds, hypertelorism, depressed nasal bridge, orofacial cleft, prominent jaw), hearing loss and developmental delay. Males usually present a more severe phenotype than females and rarely survive. Diagnostic suspicion is based o…
The human X chromosome is enriched for germline genes expressed in premeiotic germ cells of both sexes.
2006
The role of X-chromosomal genes in spermatogenesis has been subject to a number of studies in different organisms. Recently, it was proposed that the X chromosome has a predominant role in premeiotic stages of mammalian spermatogenesis. We analyzed the expression of a representative set of 17 X-linked and 48 autosomal germline-restricted genes in different stages of human germ cell development. In accordance with data from other species, we show that the human X chromosome is indeed significantly enriched for genes activated in premeiotic stages of spermatogenesis. In contrast to recent studies, however, we found that expression of these genes is not restricted to spermatogenesis, but is ac…
Disease manifestations and X inactivation in heterozygous females with Fabry disease
2006
Aim: Fabry disease is an X-linked lysosomal storage disorder characterized by an accumulation of neutral glycosphingolipids in multiple organ systems caused by α-galactosidase A deficiency due to mutations in the GLA gene. The majority of heterozygous females show the characteristic signs and symptoms of the disease, and some of them are severely affected. The current hypothesis for the occurrence of disease manifestations in females is skewed X inactivation favouring the mutant GLA allele. Method: We analyzed the patterns of X inactivation in the leukocytes of 28 biochemically and genetically characterized symptomatic Fabry disease heterozygotes and their correlation with clinical and bioc…