Familial CHARGE syndrome and the CHD7 gene: A recurrent missense mutation, intrafamilial recurrence and variability

Autor: Marjolijn C.J. Jongmans, Kim P. van der Donk, Lies H. Hoefsloot, Ingrid M.B.H. van de Laar, Conny M.A. van Ravenswaaij, Han G. Brunner, Ian Walpole, Yvonne M.C. Hendriks, Ronald J.C. Admiraal, Joke B. G. M. Verheij, Alex Magee
Přispěvatelé: Clinical Genetics
Rok vydání: 2008
Předmět:
ANOMALIES
Male
Genetics and epigenetic pathways of disease [NCMLS 6]
Somatic cell
PHENOTYPIC SPECTRUM
Germline mosaicism
CHD7
Exon
CHARGE syndrome
Perception and Action [DCN 1]
Neurosensory disorders [UMCN 3.3]
Missense mutation
mild phenotype
Conserved Sequence
Genetics (clinical)
Genes
Dominant
Genetics
Mosaicism
familial
ASSOCIATION
Syndrome
Phenotype
Pedigree
DNA-Binding Proteins
Mutation (genetic algorithm)
HYPOGONADISM
Female
Molecular Sequence Data
Mutation
Missense
HEART-DISEASE
Biology
Arginine
Genomic disorders and inherited multi-system disorders [IGMD 3]
Germline mutation
Diseases in Twins
medicine
Humans
Abnormalities
Multiple
Amino Acid Sequence
Sequence Homology
Amino Acid
Siblings
DNA Helicases
Genetic Variation
Sequence Analysis
DNA
Twins
Monozygotic
medicine.disease
Genetic defects of metabolism [UMCN 5.1]
Amino Acid Substitution
Case-Control Studies
Immunity
infection and tissue repair [NCMLS 1]
Zdroj: American Journal of Medical Genetics Part A, 146A(1), 43-50. Wiley-Liss Inc.
American Journal of Medical Genetics. Part A, 146A, 43-50
American Journal of Medical Genetics. Part A, 146A, 1, pp. 43-50
American Journal of Medical Genetics. Part A, 146A(1), 43-50. Wiley
ISSN: 1552-4825
Popis: Contains fulltext : 70271.pdf (Publisher’s version ) (Closed access) CHARGE syndrome is an autosomal dominant condition that is caused by mutations in the CHD7 gene. Few familial cases of this syndrome have been reported and these were characterized by a wide clinical variability. We here report on five CHD7 mutation positive families and comment on their clinical features. We observed somatic and germline mosaicism as well as parent-to-child transmission of non-mosaic CHD7 mutations as causes of familial CHARGE syndrome. In one family with two affected sibs a somatic mutation was identified in lymphocytes of a clinically unaffected parent (2520G > A in exon 8). This is the second report of somatic CHD7 mosaicism in an unaffected parent. In two further families with affected siblings, we could not detect the mutation in parental lymphocytes suggesting germline mosaicism. The previously reported clinical variability was strikingly present in all five families. We find that alterations in CHD7 can result in a very mild phenotype, characterized by only a few minor symptoms of the CHARGE syndrome clinical spectrum. Such a mild phenotype was present in two families that shared the same 6322G > A missense mutation. These two families showed parent-to-child transmission. Phenotypically milder forms of CHARGE syndrome have a higher risk of transmission to multiple family members.
Databáze: OpenAIRE
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