Identification of 54 large deletions/duplications in TSC1 and TSC2 using MLPA, and genotype-phenotype correlations.

Identification of 54 large deletions/duplications in TSC1 and TSC2 using MLPA, and genotype-phenotype correlations. Research Abstract Details 

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Identification of 54 large deletions/duplications in TSC1 and TSC2 using MLPA, and genotype-phenotype correlations. Abstract Text:

Piotr Kozlowski,Penelope Roberts,Sandra Dabora,David Franz,John Bissler,Hope Northrup,Kit Sing Au,Ross Lazarus,Dorota Domanska-Pakiela,Katarzyna Kotulska,Sergiusz Jozwiak,David J Kwiatkowski,

Tuberous sclerosis (TSC) is an autosomal dominant disorder caused by mutations in either of two genes, TSC1 and TSC2. Point mutations and small indels account for most TSC1 and TSC2 mutations. We examined 261 TSC DNA samples (209 small-mutation-negative and 52 unscreened) for large deletion/duplication mutations using multiplex ligation-dependent probe amplification (MLPA) probe sets designed to permit interrogation of all TSC1/2 exons, as well as 15-50 kb of flanking sequence. Large deletion/duplication mutations in TSC1 and TSC2 were identified in 54 patients, of which 50 were in TSC2, and 4 were in TSC1. All but two mutations were deletions. Only 13 deletions were intragenic in TSC2, and one in TSC1, so that 39 (73%) deletions extended beyond the 5', 3' or both ends of TSC1 or TSC2. Mutations were identified in 24% of small-mutation-negative and 8% of unscreened samples. Eight of 54 (15%) mutations were mosaic, affecting 34-62% of cells. All intragenic mutations were confirmed by LR-PCR. Genotype/phenotype analysis showed that all (21 of 21) patients with TSC2 deletions extending 3' into the PKD1 gene had kidney cysts. Breakpoints of intragenic deletions were randomly distributed along the TSC2 sequence, and did not preferentially involve repeat sequence elements. Our own 20-plex probe sets gave more robust performance than the 40-plex probe sets from MRC-Holland. We conclude that large deletions in TSC1 and TSC2 account for about 0.5 and 6% of mutations seen in TSC patients, respectively, and MLPA is a highly sensitive and accurate detection method, including for mosaicism.

Identification of 54 large deletions/duplications in TSC1 and TSC2 using MLPA, and genotype-phenotype correlations. Publishing Authors By Initials

P Kozlowski,P Roberts,S Dabora,D Franz,J Bissler,H Northrup,KS Au,R Lazarus,D Domanska-Pakiela,K Kotulska,S Jozwiak,DJ Kwiatkowski,

For similar proteins: neoplasm proteins: tumor suppressor proteins research abstracts see: proteins: neoplasm proteins: tumor suppressor proteins research

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Identification of 54 large deletions/duplications in TSC1 and TSC2 using MLPA, and genotype-phenotype correlations. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Human genetics

VOLUME: 121

Page Numbers: 389-400

Journal Abbreviation:

ISSN: 0340-6717

DAY: 8

MONTH: 02

YEAR: 2007

Identification of 54 large deletions/duplications in TSC1 and TSC2 using MLPA, and genotype-phenotype correlations. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7613873

Identification of 54 large deletions/duplications in TSC1 and TSC2 using MLPA, and genotype-phenotype correlations. Keywords Mesh Terms:

KEYWORDS: Tumor Suppressor Proteins

MESH TERMS: genetics

Chemical & Substance for Abstract: Identification of 54 large deletions/duplications in TSC1 and TSC2 using MLPA, and genotype-phenotype correlations. Information

Substance Name: tuberous sclerosis complex 2 protein

Registry Number: 169027-60-5

Grant and Affiliation Information for Identification of 54 large deletions/duplications in TSC1 and TSC2 using MLPA, and genotype-phenotype correlations.

AFFILIATION: Genetics Laboratory, Division of Translational Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Country: Germany

AGENCY: United States NINDS

GRANT: NS31535

ACRONYM: NS

MEDLINETA: Hum Genet

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