Abstract:
:Mutations in genes involved in Ras signalling cause Noonan syndrome and other disorders characterised by growth disturbances and variable neuro-cardio-facio-cutaneous features. We describe two sisters, 46 and 31 years old, who presented with dysmorphic features, hypotonia, feeding difficulties, retarded growth and psychomotor retardation early in life. The patients were initially diagnosed with Costello syndrome, and autosomal recessive inheritance was assumed. Remarkably, however, we identified a germline HRAS mutation (G12A) in one sister and a germline KRAS mutation (F156L) in her sibling. Both mutations had arisen de novo. The F156L mutant K-Ras protein accumulated in the active, guanosine triphosphate-bound conformation and affected downstream signalling. The patient harbouring this mutation was followed for three decades, and her cardiac hypertrophy gradually normalised. However, she developed severe epilepsy with hippocampal sclerosis and atrophy. The occurrence of distinct de novo mutations adds to variable expressivity and gonadal mosaicism as possible explanations of how an autosomal dominant disease may manifest as an apparently recessive condition.
journal_name
J Med Genetjournal_title
Journal of medical geneticsauthors
Søvik O,Schubbert S,Houge G,Steine SJ,Norgård G,Engelsen B,Njølstad PR,Shannon K,Molven Adoi
10.1136/jmg.2007.049361subject
Has Abstractpub_date
2007-07-01 00:00:00pages
e84issue
7eissn
0022-2593issn
1468-6244pii
44/7/e84journal_volume
44pub_type
杂志文章abstract::Pericentric inversions in chromosome 2 were traced in 2 unrelated North American black families. In the case of inv(2)(p13q11) no effect on reproduction was observed. In the case of inv(2)(p11q13) some reproductive abnormalities were noted which might be related to the inversion. ...
journal_title:Journal of medical genetics
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更新日期:1978-10-01 00:00:00
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journal_title:Journal of medical genetics
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更新日期:1991-08-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章,评审
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更新日期:2015-05-01 00:00:00
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更新日期:1994-06-01 00:00:00
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doi:10.1136/jmg.2004.029462
更新日期:2005-10-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章
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更新日期:2005-09-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章,评审
doi:10.1136/jmg.35.3.238
更新日期:1998-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1136/jmg.29.6.425
更新日期:1992-06-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.14.5.339
更新日期:1977-10-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.33.9.726
更新日期:1996-09-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.16.5.358
更新日期:1979-10-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2017-104779
更新日期:2017-12-01 00:00:00
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更新日期:1981-04-01 00:00:00
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journal_title:Journal of medical genetics
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更新日期:1991-03-01 00:00:00
abstract:OBJECTIVES:Current technologies for delivering gene testing are labour-intensive and expensive. Over the last 3 years, new high-throughput DNA sequencing techniques (next generation sequencing; NGS), with the capability to analyse multiple genes or entire genomes, have been rapidly adopted into research. This study exa...
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更新日期:2012-05-01 00:00:00