China
Africa
Explore chapters and articles related to this topic
An Approach to Inherited Pulmonary Disease
Published in Stephen D. Litwin, Genetic Determinants of Pulmonary Disease, 2020
Dominant and recessive phenotypes caused by genes on the X chromosome show distinctive patterns of inheritance that are often easily recognized. Human males are described as hemizygous with respect to the loci on the X chromosome, since they have only one chromosome, and thus only one gene at each locus on the X. X-linked phenotypes which are usually recessive in females who are heterozygous for the causative gene are expressed in hemizygous males who carry a single dose of the same gene because that is the only gene present that codes for that function. The resulting pedigrees of rare X-linked phenotypes show affected males whose sisters have affected sons (Fig. Id). Expression of the phenotype in a female could be due to homozygosity for the causative gene or to an unusual proportion of inactivated X chromosomes (see Lyon phenomenon described below).
Genetic and genomic investigations
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
Females may manifest full expression of a mutation, as if they were male, under particular circumstances, including genes in which mutations cause disease through a dominant negative mechanism; marked skewing of X-chromosome inactivation towards inactivation of the intact allele (perhaps by chance); homozygosity for mutation in an X-chromosome gene (e.g. where the mutant allele is common, or in the context of consanguinity); Turner syndrome; and disruption of the gene by a balanced translocation between the X chromosome and an autosome.
Muscle, Bone, and Skin Disorders
Published in Victor A. Bernstam, Pocket Guide to GENE LEVEL DIAGNOSTICS in Clinical Practice, 2019
A total or partial deletion of the RB gene has been detected in 43% of the cases. The LOH on chromosome 13 by either homozygosity or hemizygosity was found in 64% of all informative cases, including those without detectable structural alteration of the RB gene. The highest frequency (77%) of LOH on other chromosomes was detected particularly for chromosome 17.
Diagnostic Utility of Array Comparative Genomic Hybridization in Children with Neurological Diseases
Published in Fetal and Pediatric Pathology, 2022
It is noteworthy that the majority of cases referred to the genetic laboratory for aCGH analysis in our study group were male (63.2%). However, the gender frequency for causative CNVs was nearly the same (Table 1). In light of current information and contrary to our predictions, there was no aggregation on the X chromosome in terms of pathogenicity. The human X chromosome contains more genes related to cognitive disturbance compared with other chromosomes and the majority of genes identified in disease etiology like ID and NDD are on the X chromosome. Therefore diseases like ID and NDD associated with the X chromosome have higher potential for phenotypic occurrence in the male gender due to hemizygosity [15]. In the past years, genetic analyses especially for ID etiology focused more on the X chromosome and an OMIM-based research showed the X chromosome had higher rates of bias for ID [16]. However, currently, detailed analyses like aCGH reveal genomic rearrangements apart from the X chromosome at considerable rates for disease etiology like ID, NDD, and ASDs. Recently array studies report that only 10–15% of ID can be explained by mutations on the X chromosome [17]. As a result, more detailed submicroscopic array analyses like aCGH are actually a historical and technological process of reducing X chromosome bias in diseases like ID, NDD, and ASDs. It is proposed that the growing popularity of aCGH analyses and discovery of submicroscopic deletions and duplications apart from the X chromosome may even change classifications like X-linked mental retardation in the near future.
Five New Cases of Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome (MMIHS), with One Case Showing a Novel Mutation
Published in Fetal and Pediatric Pathology, 2021
Alyssa Kalsbeek, Renee Dhar-Dass, Abdul Hanan, Eman Al-Haddad, Iman William, Adina Alazraki, Janet Poulik, Kasey McCollum, Aya Almashad, Bahig M. Shehata
After obtaining IRB approval following diagnosis of the first case, we renewed on a yearly basis until additional cases were identified. After the first diagnosis three more cases of MMIHS were identified and a fourth was identified in our files. Autopsies were performed for the first four cases and histological specimens collected from the infants were reviewed and examined to confirm the diagnosis in addition to radiological findings. Molecular analyses were performed on peripheral blood previously attained. DNA sequencing and gene identification was accomplished through various methods. Family history was not significant for MMIHS in any of the five examined cases with only one having a history of consanguinity. Homozygosity mapping method was used since this method identifies blocks of homozygous DNA in the genome-wide search, and even common recessive traits are more likely to be present in a homozygous state [7,8]. Sanger sequencing using primers and polymerase chain reaction (PCR) was used to confirm the candidate single nucleotide polymorphisms (SNPs) using DNA from the patient and the parents. Forward and reverse sequencing of the target DNA regions were performed.
Psychopharmacology of Williams syndrome: safety, tolerability, and effectiveness
Published in Expert Opinion on Drug Safety, 2021
Robyn P. Thom, Barbara R. Pober, Christopher J. McDougle
Psychiatric symptoms, particularly inattention, hyperactivity, anxiety, and sleep problems are very common among children, adolescents, and adults with WS. Indeed, on structured diagnostic interview, more than 80% of individuals with WS met criteria for at least one Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis in two separate studies [11,12]. Psychiatric symptoms are the main determinant of quality of life for individuals with WS [3]. Intellectual disability, the uneven cognitive profile, and increased affiliative drive accompanied by social skill vulnerabilities, may predispose individuals with WS to developing psychiatric disorders. In addition to psychosocial vulnerabilities, hemizygosity for certain genes within the microdeletion, such as GTF2I, likely also increase the risk of psychopathology [13].