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Adrenoleukodystrophy
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
The cholesterol esters found in the adrenal glands contain large amounts of very long-chain fatty acids (VLCFA) [8]. Moser and colleagues [14, 15] found that these elevated VLCFA could be demonstrated in blood and cultured fibroblasts, and this has become the method of choice for diagnosis. They can be demonstrated by gas chromatography and gas chromatography-mass spectrometry (GCMS). The oxidation of VLCFA takes place in peroxisomes. The enzyme that catalyzes the formation of the CoA esters of these VLCFAs is defective in this disorder (Figure 62.1) [16, 17]. However, the defective gene is that of a peroxisomal membrane transporter protein [18]. The gene was mapped to Xq28 [19]. It was isolated and found to be a member of the ABC transporter family [18, 20]. Of more than 200 mutations identified, approximately 50 percent were missense and 24 percent frameshifts; large deletions, insertions, and splicing defects are uncommon [21–23]. The gene is now referred to as ABCD1 and its product as ALDP.
Genodermatoses affecting the nail
Published in Eckart Haneke, Histopathology of the NailOnychopathology, 2017
Dyskeratosis congenita (DC) of Zinsser-Cole-Engman (OMIM 305000) is an inherited bone marrow failure and cancer predisposition syndrome characterized by germline mutations in telomere biology. It can be inherited as an X-linked, autosomal dominant (AD) (on chromosome Xq28), or autosomal recessive (AR) type (OMIM 615190, 224239). De novo germline mutations are rather frequent in DC. About 70% of DC patients have an identifiable germline mutation.94 It is clinically heterogeneous and usually diagnosed by the mucocutaneous triad of progressively dystrophic nails, abnormal pigmentation, and leukoplakias of the oral mucosa, often associated with severe periodontitis. Hoyeraal–Hreidarsson syndrome (HH) is a clinically severe variant of DC also including cerebellar hypoplasia, immunodeficiency, and intrauterine growth retardation.95 The germline mutation is in one of nine genes, the products of which are all involved in telomere biology. DC is very rare with an annual incidence of <1 per million. Patients with DC show considerable disease diversity in terms of age at onset, symptoms, and severity. Even with the same gene mutation, the disease manifestations are variable making it sometimes difficult to reach a correct diagnosis.96 Due to the heredity pattern, females may have less severe clinical features.97 Approximately 90% of patients suffer from nail dystrophy affecting the fingernails first and then the toenails. It begins with ridging and longitudinal splitting and gradually progresses, resulting in small, rudimentary, or absent nails.
Accident and Emergency
Published in Nagi Giumma Barakat, Get Through, 2006
A 3-month-old baby is not gaining weight, and his urine osmolarity shows <100mosmol/kg. Oxytocin is normal, but the vasopressin level is low. A genetic study shows an abnormal gene on Xq28. A 3-year-old boy is seen with a history of polydipsia and polyuria. His cranial MRI is normal, and his urine osmolar-ity rises to 300 mosmol/l after he is given DDAVP, as well as with a water deprivation test.
To What Extent are Prenatal Androgens Involved in the Development of Male Homosexuality in Humans?
Published in Journal of Homosexuality, 2022
The Xq28 locus, which has been consistently named as potentially linked to male homosexuality through genome-wide association studies (Hamer et al., 1993; Sanders et al., 2015), encodes the MAGE-A11 protein, which increases androgen receptor transcription by binding directly to its gene (Liu, Su, Blackwelder, Minges, & Wilson, 2011). Differences in its expression could alter region-specific androgen signaling (Balthazart & Court, 2017), thus inducing regional changes in brain structure and function. Although no difference has been identified in areas influencing sexual orientation, such as the hypothalamus, this prospect merits further analysis. However, as other loci have been implicated, including the pericentric region of chromosome 8 and the SLITRK proteins on chromosome 13 (Sanders et al., 2017), which influence brain development, as well as 5 other autosomal loci associated with same-sex sexual behavior (Ganna et al., 2019), male homosexuality is probably influenced by multiple genetic factors. Interestingly, no relationship has been identified between male homosexuality and the SRD5A genes encoding 5α-reductase isoforms or the androgen receptor gene, thus DHT probably has less of a role in this development.
Visual and ocular findings in a family with X-linked cone dysfunction and protanopia
Published in Ophthalmic Genetics, 2021
Dag Holmquist, David Epstein, Monica Olsson, Bernd Wissinger, Susanne Kohl, Jürg Hengstler, Kristina Tear-Fahnehjelm
BED was first reported in 1988 in a single large family originating from the Danish island of Bornholm where the family members had high myopia and astigmatism, impaired visual acuity, signs of optic nerve head hypoplasia, abnormal cone electroretinography (ERG) and deutan color vision defect (1). In 1990, the phenotype was mapped to the tip of the q-arm of the X-chromosome at Xq28 by linkage analysis and became the first locus identified for high myopia (MYP1) (2). Xq28 contains the long- (L, “red”) and middle-wavelength (M, “green”) sensitive opsin gene array, harbouring the OPN1LW and OPN1MW genes, respectively. Studies have identified common gene rearrangements, deletions and point mutations at the opsin gene array accounting for cone photoreceptor dysfunction and color vision defects, namely protanopia, deuteranopia for the commonly known “red-green color blindness” but also blue cone monochromatism (BCM), a retinal disease with non-functional L and M cones (3).
IRAK1 Gene Polymorphism in Rheumatoid Arthritis
Published in Immunological Investigations, 2021
Najme Hosseini, Mohammad Taher Tahoori, Adel Mohammadzadeh, Hossein Zarei Jaliani, Morteza Bitaraf Sani, Hosein Soleimani Salehabadi
We investigated CD40 and IRAK1 gene polymorphisms in an Iranian population to answer the question whether they can affect clinical and laboratory parameters of patients. Among several loci that have been recognized to be related with RA risk using GWAS, IRAK1 is located in Xq28 locus and encodes a serine/threonine kinase mediating TLRs and IL-1 receptor (TIR family) signaling. IRAK1 is autophosphorylated upon stimulation by TIR-specific ligands and is responsible for the activation of NF-kB signaling cascade by TLR and IL1, which plays a crucial role in early inflammatory response and the expression of proinflammatory cytokines (Khalifa et al. 2017). Several polymorphisms of IRAK1 are reported to be associated with increasing susceptibility to autoimmune diseases, including systemic lupus erythematosus (Kaufman et al. 2012), systemic sclerosis (Carmona et al. 2013; Dieude et al. 2011), and RA (Chatzikyriakidou et al. 2010; Eyre et al. 2012; Zhang et al. 2013). Overall, these investigations demonstrated that Xq28 was a shared locus for various complex diseases, especially support the susceptibility to inflammatory diseases.