Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the case of a 15-year-old girl who presented to a pediatric endocrinology clinic for delayed puberty with no signs of secondary sexual development. Her past medical history was significant for bilateral colobomas, inner-ear anomalies, hearing loss, and anosmia. Genetic testing revealed a novel de novo mutation in the CHD7 gene, one of the causative genes in CHARGE syndrome (coloboma, heart disease, choanal atresia, retarded growth and development and/or central nervous system anomalies, genital anomalies and/or hypogonadism, and ear anomalies and/or deafness). We review the distinction between hypogonadotrophic hypogonadism and hypergonadotrophic hypogonadism and discuss the availability of molecular genetic testing for idiopathic hypogonadotrophic hypogonadism. CHD7 mutations have also been found in some patients with Kallmann syndrome, hypogonadotrophic hypogonadism, and anosmia, and we discuss the overlap between this syndrome and CHARGE syndrome. With the increased availability of genetic testing for a variety of disorders, it is important for pediatricians to become familiar with interpreting genetic test results. Finally, we illustrate that Bayes' theorem is a useful statistical tool for interpreting novel missense mutations of unknown significance.
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PMID:Delayed puberty due to a novel mutation in CHD7 causing CHARGE syndrome. 2104 Dec 84

In Genetics Out-patient Department of Shanghai Children's Medical Center, we consulted a 3-year-old boy with multiple anomaly syndrome (congenital heart disease, cryptorchidism, congenital deafness, mental retardation, exophthalmos, laryngeal cartilage dysplasia and high arched palate). We ruled out the possibility of multiple deformities caused by genomic imbalances. The patient was then clinically considered to have CHARGE syndrome, an autosomal dominant multi-system disorder involving defects in multiple organs, and CHD7 is the only known gene associated with the syndrome. Sequencing analysis of CHD7 of the proband identified a de novo heterogeneous mutation (c.2916_2917del, p.Gln972HisfsX22), a two-nucleotide deletion causing reading frame shift and resulting in a truncated CHD7 protein. Computational structure analysis suggests that the truncated protein only contains the chromodomains of CHD7, but lacks the SWI2/SNF2-like ATPase/helicase domain and the DNA binding domain, which are indispensable for the proper function of the protein, especially on chromatin remodeling. The patient then received follow up treatment in different clinical departments in a long period. To our best knowledge, this is the first CHARGE syndrome in Chinese patients diagnosed by gene analysis. In summary, the clinical symptoms and the description of treatment in the present case, combined with genetic test and functional prediction of CHD7, are helpful for further understanding and genetic counseling of the CHARGE syndrome.
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PMID:A novel CHD7 mutation in a Chinese patient with CHARGE syndrome. 2560 31

CHARGE syndrome (CS) is a genetic disorder whose first description included Coloboma, Heart disease, Atresia of choanae, Retarded growth and development, Genital hypoplasia, and Ear anomalies and deafness, most often caused by a genetic mutation in the CHD7 gene. Two features were then added: semicircular canal anomalies and arhinencephaly/olfactory bulb agenesis, with classification of typical, partial, or atypical forms on the basis of major and minor clinical criteria. The detection rate of a pathogenic variant in the CHD7 gene varies from 67% to 90%. To try to have an overview of this heterogenous clinical condition and specify a genotype-phenotype relation, we conducted a national study of phenotype and genotype in 119 patients with CS. Selected clinical diagnostic criteria were from Verloes (2005), updated by Blake & Prasad (). Besides obtaining a detailed clinical description, when possible, patients underwent a full ophthalmologic examination, audiometry, temporal bone CT scan, gonadotropin analysis, and olfactory-bulb MRI. All patients underwent CHD7 sequencing and MLPA analysis. We found a pathogenic CHD7 variant in 83% of typical CS cases and 58% of atypical cases. Pathogenic variants in the CHD7 gene were classified by the expected impact on the protein. In all, 90% of patients had a typical form of CS and 10% an atypical form. The most frequent features were deafness/semicircular canal hypoplasia (94%), pituitary defect/hypogonadism (89%), external ear anomalies (87%), square-shaped face (81%), and arhinencephaly/anosmia (80%). Coloboma (73%), heart defects (65%), and choanal atresia (43%) were less frequent.
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PMID:Phenotype and genotype analysis of a French cohort of 119 patients with CHARGE syndrome. 2917 47