Trisomy Disorders

Trisomy 17

Posted on: October 30, 2008

Trisomy 17 is extremely rare and there is little information available on it.  I was able to locate some abstracts and am posting them.

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Trisomy 17 mosaicism

Oct 1, 2005

Trisomy 17p10-p12 due to mosaic supernumerary marker chromosome: delineation of molecular breakpoints and clinical phenotype, and comparison to other proximal 17p segmental duplications.Yatsenko SA, Treadwell-Deering D, Krull K, Lewis RA, Glaze D, Stankiewicz P, Lupski JR, Potocki L.

 

The unstable, gene-rich chromosome region 17p11.2-p12 is associated with various structural aberrations including supernumerary marker chromosomes (SMCs). In some cases, SMC(17)s utilize the same substrates for recombination as the common recurrent 17p11.2 and 17p12 rearrangements. We report on a 9-year-old girl with a de novo mosaic SMC(17). The der(17) encompasses genetic material from 17p10-p11.2 and is present in 97% of peripheral blood lymphocytes and in 79% of buccal cells. The patient has few features similar to individuals with duplication 17p11.2 including mental retardation, language impairment, and sleep disturbances but has normal growth, and no structural abnormalities of the heart, kidneys, or brain. She has no substantial behavioral abnormalities or dysmorphic features. Molecular analyses determined that the der(17) contains RAI1 but not PMP22. We found one chromosome breakpoint within the centromere and the second breakpoint within the distal Smith-Magenis syndrome low-copy repeat (distal SMS-REP). Recently we characterized the breakpoints of three other marker chromosomes originating from the proximal short arm of chromosome 17. In all four cases, one breakpoint maps within the centromere and in three cases the second breakpoint maps within a low-copy repeat. We thus propose that genome architecture may play a significant role in the formation of marker chromosomes. We present the cytogenetic, molecular, and clinical data of this patient and compare our results with those of patients with dup(17)(p11.2p11.2) syndrome and other patients with SMC(17). (c) 2005 Wiley-Liss, Inc.

Publication Types:

PMID: 16152635 [PubMed – indexed for MEDLINE]

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Small marker chromosomes in two patients with segmental aneusomy for proximal 17p.

June 2004

Shaw CJ, Stankiewicz P, Bien-Willner G, Bello SC, Shaw CA, Carrera M, Perez Jurado L, Estivill X, Lupski JR.

Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Room 604B, TX 77030, Houston, USA.

We report a nine-year-old girl (patient 1934) and a five-year-old boy (patient 2170) with small, de novo supernumerary marker chromosomes (SMCs) derived from proximal 17p. The clinical features of patient 1934 include developmental delay, triangular face, prominent forehead, low set ears, dental abnormalities, a high arched palate, long, flexible fingers, and joint laxity. Patient 2170 is affected with developmental delay, oral-motor dyspraxia/verbal apraxia, thick upper and lower lips, bilateral fifth finger clinodactyly, joint laxity and mild hypotonia. G-banded chromosome analysis of patient 1934 revealed mosaicism for a SMC in 72% of peripheral lymphocytes analyzed, whereas analysis of patient 2170 identified a smaller SMC present in 100% of cells analyzed. Fluorescence in situ hybridization (FISH) studies demonstrated that both of the SMCs derived from 17p10-p11.2. Using FISH and array-CGH analysis, the proximal breakpoints mapped within the centromere and the distal breakpoints were both located within the Smith-Magenis syndrome (SMS) common deletion region. We compare the clinical characteristics of our patients with those previously reported to have either SMC including 17p or duplications of proximal 17p in an effort to further delineate the phenotype of trisomy 17p10-p11.2 and to elucidate genotype-phenotype correlations.

Publication Types

PMID: 15098121 [PubMed – indexed for MEDLINE]

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A girl with duplication 17p10-p12 associated with a dicentric chromosome.

Jan 2004

Shaw CJ, Stankiewicz P, Christodoulou J, Smith E, Jones K, Lupski JR.

 

PMID: 14699617 PubMed – indexed for MEDLINE]

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Trisomy 17p10-p12 resulting from a supernumerary marker chromosome derived from chromosome 17: molecular analysis and delineation of the phenotype.

June 2003

Stankiewicz P, Parka SS, Holder SE, Waters CS, Palmer RW, Berend SA, Shaffer LG, Potocki L, Lupski JR.

 

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.

We report a 7 1/2-year-old girl with an approximately 9.5 Mb duplication of proximal 17p. Her clinical features include moderately severe developmental delay, absence of speech, talipes, congenital dislocation of the hips, premature adrenarche, dysmorphic facial features, deep palmar creases, and signs and symptoms of peripheral neuropathy consistent with Charcot-Marie-Tooth disease type 1A (CMT1A). Chromosome analysis revealed a partially duplicated 17p with two centromeres on the derivative chromosome. Fluorescence in situ hybridization (FISH) analysis demonstrated the tandemly duplicated segment spans 17p10-p12, including the entire Smith-Magenis syndrome (SMS) critical region and a portion of the CMT1A critical region. One breakpoint mapped within the centromere and the second breakpoint mapped within the CMT1A critical region, distal to the PMP22 gene. Microsatellite polymorphism studies showed that the duplicated chromosome is of maternal origin. We compare the clinical features of our patient to those of individuals with partial trisomy of proximal 17p to further delineate the genotype-phenotype correlation associated with segmental duplication of this chromosomal region. Copyright 2003 Wiley-Liss, Inc.

Publication Types:

Publication Types:

PMID: 14699617 – PubMed

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Trisomy 17p10-p12 resulting from a supernumerary marker chromosome derived from chromosome 17: molecular analysis and delineation of the phenotype.

June 2003

Stankiewicz P, Parka SS, Holder SE, Waters CS, Palmer RW, Berend SA, Shaffer LG, Potocki L, Lupski JR

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Department of Molecular and Human Genetics, Baylor College of Medicine, Houston TX 77030-3498, USA.

 

We report a 5-year-old boy with a small de novo marker chromosome derived from the proximal short arm of chromosome 17. His clinical features include hypotonia, global developmental delay, oval face with large nose and prominent ears, and ligamentous laxity of the fingers. Magnetic resonance imaging of the brain demonstrated mildly delayed myelination. G-band chromosome analysis revealed mosaicism for a small marker chromosome in 85% of the peripheral blood cells analyzed. Fluorescence in situ hybridization and microsatellite polymorphism studies showed that the der(17) was of maternal origin and included genetic material from the 17p10-p12 region, but did not contain the PMP22 gene. One breakpoint mapped within the centromere and the second breakpoint mapped adjacent to the Charcot-Marie-Tooth disease type 1A proximal low-copy repeat (CMT1A-REP). We compare the clinical characteristics of our patient with those previously reported to have a duplication involving the proximal short arm region of chromosome 17 to further delineate the phenotype of trisomy 17pl0-p12.

Publication Types:

Case Reports

PMID: 11903333 [PubMed – indexed for MEDLINE]

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Cerebellar hypoplasia, zonular cataract, and peripheral neuropathy in trisomy 17 mosaicism.

Terhal P, Sakkers R, Hochstenbach R, Madan K, Rabelink G, Sinke R, Giltay J

Department of Biomedical Genetics, University Medical Center Utrecht, PO Box 85090, Utrecht, The Netherlands. p.a.terhal@dmg.azu.nl

Trisomy 17 mosaicism in liveborns is an extremely rare chromosomal abnormality, with only three cases reported in the literature. Here we describe a 7-year-old boy with trisomy 17 mosaicism. The chromosome abnormality was detected by amniocentesis and was confirmed postnatally in cultured skin fibroblasts. The main clinical features were mental retardation and growth reduction, peripheral motor and sensory neuropathy, hypoplastic cerebellar vermis, zonular cataract, and body asymmetry. In our patient, and in the three earlier described cases, the additional chromosome 17 was detected in skin fibroblasts, not in peripheral lymphocytes. Molecular investigations excluded uniparental disomy of chromosome 17 in our patient. The extra chromosome 17 probably originated from a postzygotic mitotic nondisjunction of the maternal chromosome 17. In most cases of trisomy 17 mosaicism detected in amniocytes the chromosome abnormality seems to be confined to extra-embryonic tissues and clinically normal children are born. If, however, there are also ultrasound abnormalities, the possibility of fetal trisomy 17 mosaicism should certainly be considered. If postnatal karyotyping is limited to blood the diagnosis of trisomy 17 mosaicism could easily be missed. Therefore, we recommend chromosome analysis to be based on cultured skin fibroblasts in all cases where mental retardation is accompanied by postnatal growth retardation, body asymmetry, peripheral neuropathy, and cerebellar hypoplasia or zonular cataract.

Amniocentesis Research Today

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Name of Stem Cell Line: UC01 (HSF-1)

Initial characterization of HSF-1 identified a human embryonic stem cell line with a normal 46XY karyotype. After extensive expansion and analysis, however, a small subset of the cells (<5%) were found to have a 47XY karyotype due to the presence of a third copy of chromosome 17. No other abnormal karyotypes have been detected in HSF-1 cells. The presence of trisomy 17 could be due to the presence of trisomy 17 cells in the embryo at the time of derivation of the cell line, a conclusion supported by the presence of low numbers of trisomy in the earliest passages tested for the line.

To determine whether the karyotype was stable, and to isolate a subline of HSF-1 with a normal karyotype that could be used for research purposes, the line was then cultured from single cells of the earliest frozen passage (p11). Expanded subclones were karyotyped, and more than 200 cells were assessed for trisomy 17 for each subcloned line. The first two subcloned lines tested exhibited a normal karyotype. HSF-1 Clone 14 (HSF-1.14), one of these two lines, has now been expanded further to passage 29 and characterized fully. This subline was subjected to karyotypic analysis of 20 individual cells at mitosis, all giving a normal 46XY count. Further testing of the cells was done by interphase FISH analysis of chromosome 17, as well as chromosome 18 as a control. After counting chromosomes from 300 cells, no trisomy 17 cells were detected, further supporting the conclusion that this line has a stable karyotype. We suggest, however, routine analysis to ensure that the karyotype remains normal.

See also:
Expression Analysis
Genotype
Immunohistochemistry
Karyotype

UCSF

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