MedGen

Chronic lymphocytic leukemia (CLL) is a common neoplasia of B lymphocytes in which these cells progressively accumulate in the bone marrow, blood, and lymphoid tissues. The clinical evolution of the disorder is heterogeneous, with some patients having indolent disease and others having aggressive disease and short survival (summary by Quesada et al., 2012). Genetic Heterogeneity of Susceptibility to Chronic Lymphocytic Leukemia Susceptibility loci have been mapped to chromosomes 11p11 (CLLS1; 609630) and 13q14 (CLLS2; 109543) by genomewide linkage analysis and translocation studies, respectively. Susceptibility mapping to chromosome 9q34 (CLLS3; 612557) is associated with downregulation of the DAPK1 gene (600831). Genomewide association studies have identified susceptibility loci on chromosomes 6p25.3 (CLLS4; 612558) and 11q24.1 (CLLS5; 612559). [from OMIM]

This syndrome has characteristics of anophthalmia or microphthalmia, retinal dystrophy, and/or myopia, associated in some cases with cerebral anomalies. It has been described in two families. Polydactyly may also be present. Linkage analysis allowed identification of mutations in the BMP4 gene, which has already been shown to play a role in eye development. [from SNOMEDCT_US]

Kawasaki disease is an acute, self-limited vasculitis of infants and children characterized by prolonged fever unresponsive to antibiotics, polymorphous skin rash, erythema of the oral mucosa, lips, and tongue, erythema of the palms and soles, bilateral conjunctival injection, and cervical lymphadenopathy (Kawasaki, 1967). Coronary artery aneurysms develop in 15 to 25% of those left untreated (Kato et al., 1975, 1996), making Kawasaki disease the leading cause of acquired heart disease among children in developed countries. Treatment with intravenous immunoglobulin (IVIg) abrogates the inflammation in approximately 80% of affected individuals and reduces the aneurysm rate to less than 5%. Cardiac sequelae of the aneurysms include ischemic heart disease, myocardial infarction, and sudden death. Epidemiologic features such as seasonality and clustering of cases suggested an infectious trigger, although no pathogen had been isolated. Several lines of evidence suggested the importance of genetic factors in disease susceptibility and outcome. First, the incidence of Kawasaki disease is 10 to 20 times higher in Japan than in Western countries (Cook et al., 1989). Second, the risk of Kawasaki disease in sibs of affected children is 10 times higher than in the general population, and the incidence of Kawasaki disease in children born to parents with a history of Kawasaki disease is twice as high as that in the general population (Fujita et al., 1989; Uehara et al., 2003). Hata and Onouchi (2009) reviewed current knowledge on Kawasaki disease, including epidemiology, genomewide linkage analysis, and molecular genetics. [from OMIM]

Stature (adult height) is an example of a complex genetic trait involving multiple genetic loci. Although complex traits are often difficult to study by linkage analysis, Hirschhorn et al. (2001) suggested that stature is a suitable complex trait for study because of the high heritability and the relatively limited contribution of environmental factors. Thus, linkage analysis has been used to identify quantitative trait loci for stature (STQTL) including STQTL1 on chromosome 6q24, STQTL2 (606256) on chromosome 7q31-q36, STQTL3 (606257) on chromosome 12p11-q14, STQTL4 (606258) on chromosome 13q32-q33, STQTL5 (608982) on chromosome 3p26, STQTL6 (300591) on chromosome Xq24, STQTL7 (609822) on chromosome 1p21, STQTL8 (610114) on chromosome 9q22, STQTL9 (611547) on chromosome 12q14.3, STQTL10 (612221) on chromosome 3q23, STQTL11 (612223) on chromosome 7q21-q22, STQTL12 (612224) on chromosome 4q28-q32, STQTL13 (612226) on chromosome 4p13.3, STQTL14 (612228) on chromosome 20q11.22, STQTL15 (612578) on chromosome 8q21.13, STQTL16 (612579) on chromosome 15q22.31, STQTL17 (612737) on chromosome 7p15, STQTL18 (612892) on chromosome 6p22.1, STQTL19 (612893) on chromosome 6p21.31, STQTL20 (612894) on chromosome 13q14.3, STQTL21 (613440) on chromosome 2q37.1, STQTL22 (613547) on chromosome 16q24, STQTL23 (613548) on chromosome 1p32, and STQTL24 (613549) on chromosome 2p16. See also X-linked short stature (300582) associated with mutations in the SHOX gene (312865). Associations Pending Confirmation For discussion of a possible association between short stature and variation in the CYP26C1 gene, see 608428. [from OMIM]

The familial form of nonmedullary thyroid carcinoma (NMTC) is a complex genetic disorder characterized by multifocal neoplasia and a higher degree of aggressiveness than its sporadic counterpart. One peculiar form of thyroid tumors is characterized by the presence of cell oxyphilia. Oxophil cells are found in a minority of thyroid tumors, either benign or malignant. These cells show a large volume of granular eosinophilic cytoplasm and are very rich in mitochondria. The familial occurrence of thyroid tumors with cell oxyphilia was reported by Katoh et al. (1998). Canzian et al. (1998) reported such a family with affected members in 3 generations and by linkage analysis mapped the gene to 19p13. For general phenotypic information and a discussion of genetic heterogeneity of NMTC, see 188550. [from OMIM]

A primary glomerular disease with characteristics of proteinuria, type IV renal tubular acidosis, microscopic haematuria and hypertension that may lead to end-stage renal failure in the second to sixth decade of life. Fibronectin glomerulopathy may present at different ages, although mostly in adolescence or early adulthood, with typical features of a nephrotic syndrome including hypertension. Clustering of the disease within families indicates a genetic origin. In 40% of families, the disease is caused by heterozygous mutations in the FN1 gene (2q34) encoding fibronectin. Whole-genome linkage analysis in a large pedigree showed another disease locus on 1q32, however no specific candidate genes has been identified so far. Segregation with disease appearance in successive generations is consistent with an autosomal dominant pattern of inheritance with age-related penetrance. [from SNOMEDCT_US]