Clinical and molecular delineation of the 17q21.31 microdeletion syndrome.
J Med Genet
; 45(11): 710-20, 2008 Nov.
Article
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| MEDLINE
| ID: mdl-18628315
ABSTRACT
BACKGROUND:
The chromosome 17q21.31 microdeletion syndrome is a novel genomic disorder that has originally been identified using high resolution genome analyses in patients with unexplained mental retardation.AIM:
We report the molecular and/or clinical characterisation of 22 individuals with the 17q21.31 microdeletion syndrome.RESULTS:
We estimate the prevalence of the syndrome to be 1 in 16,000 and show that it is highly underdiagnosed. Extensive clinical examination reveals that developmental delay, hypotonia, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and a friendly/amiable behaviour are the most characteristic features. Other clinically important features include epilepsy, heart defects and kidney/urologic anomalies. Using high resolution oligonucleotide arrays we narrow the 17q21.31 critical region to a 424 kb genomic segment (chr17 41046729-41470954, hg17) encompassing at least six genes, among which is the gene encoding microtubule associated protein tau (MAPT). Mutation screening of MAPT in 122 individuals with a phenotype suggestive of 17q21.31 deletion carriers, but who do not carry the recurrent deletion, failed to identify any disease associated variants. In five deletion carriers we identify a <500 bp rearrangement hotspot at the proximal breakpoint contained within an L2 LINE motif and show that in every case examined the parent originating the deletion carries a common 900 kb 17q21.31 inversion polymorphism, indicating that this inversion is a necessary factor for deletion to occur (p<10(-5)).CONCLUSION:
Our data establish the 17q21.31 microdeletion syndrome as a clinically and molecularly well recognisable genomic disorder.
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Base de datos:
MEDLINE
Asunto principal:
Anomalías Múltiples
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Cromosomas Humanos Par 17
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Discapacidades del Desarrollo
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Deleción Cromosómica
Tipo de estudio:
Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
Idioma:
En
Revista:
J Med Genet
Año:
2008
Tipo del documento:
Article