Biomedical subjects

Oliver Bartsch

Publications and source records attributed to Oliver Bartsch.

34 records · Page 2Linked to original sources

PubMed2004

cDNA cloning and characterization of the human THRAP2 gene which maps to chromosome 12q24, and its mouse ortholog Thrap2.

Characterization of a balanced t(2;12)(q37;q24) translocation in a patient with suspicion of Noonan syndrome revealed that the chromosome 12 breakpoint lies in the vicinity of a novel human gene, thyroid hormone receptor-associated protein 2 (THRAP2). We therefore characterized this gene and its mouse counterpart in more detail. Human and mouse THRAP2/Thrap2 span a genomic region of about 310 and >170 kilobases (kb), and both contain 31 exons. Corresponding transcripts are approximately 9.5 kb long. Their open reading frames code for proteins of 2210 and 2203 amino acids, which are 93% identical. By northern blot analysis, human and mouse THRAP2/Thrap2 genes showed ubiquitous expression. Transcripts were most abundant in human skeletal muscle and in mouse heart. THRAP2 protein is 56% identical to human TRAP240, which belongs to the thyroid hormone receptor associated protein (TRAP) complex and is evolutionary conserved up to yeast. This complex is involved in transcriptional regulation and is believed to serve as adapting interface between regulatory proteins bound to specific DNA sequences and RNA polymerase II.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Tuberous sclerosis and polycystic kidney disease in a 3-month-old infant.

Tuberous sclerosis (TSC) is an autosomal dominantly inherited multisystemic disease characterized by the development of hamartomas predominantly in brain and kidneys. The TSC2 gene for tuberous sclerosis is localized on chromosome 16p13.3 immediately adjacent to PKD1, the gene for autosomal dominant polycystic kidney disease (ADPKD). A TSC2-PKD1 contiguous gene syndrome caused by chromosomal microdeletions disrupting both the TSC2 and PKD1 genes has been identified in patients with TSC and early-onset severe ADPKD. We report a 3-month-old Caucasian girl of non-consanguineous parents with TSC and early manifestation of ADPKD. She presented with right-sided focal seizures, two small hypopigmented areas on the left flank, and elevated blood pressure requiring antihypertensive treatment. Brain magnetic resonance imaging revealed typical signs of tuberous sclerosis and abdominal ultrasonography showed bilaterally enlarged kidneys with multiple cysts resembling those seen in ADPKD. There was no family history of renal disease or of tuberous sclerosis. Findings were highly suspicious of TSC2-PKD1 contiguous gene syndrome. Using fluorescence in situ hybridization and plasmid probe CW23, which spans the adjacent 3' regions of TSC2 and PKD1 genes, we identified a submicroscopic deletion on only one of the chromosomes 16p13.3, thus permitting the diagnosis of the TSC2-PKD1 contiguous gene syndrome.

Brain↗

PubMed2004

Retinoblastoma, pinealoma, and mild overgrowth in a boy with a deletion of RB1 and neighbor genes on chromosome 13q14.

We report on a 10-year-old boy with a normal karyotype and a chromosome 13q14 deletion of the retinoblastoma gene (RB1) by fluorescence in situ hybridization (FISH). He showed subtle signs of overgrowth, including macrocephaly, hepatomegaly, and inguinal hernia. The boy also had cryptorchism and mild developmental delay. In his first months of life, variant Wiedemann-Beckwith syndrome was tentatively suspected and he was included in a careful tumor prevention program. At the age of 11 months, bifocal retinoblastoma of the left eye was diagnosed. Pinealoma was suspected at the age of 19 months and was removed by neurosurgery at the age of 29 months. At 4 years and 4 months, the deletion of the RB1 gene was suspected on clinical grounds and was diagnosed by FISH and molecular studies. At that time, he was a near-normal healthy playful kindergarten child, height 107 cm (-0.3 SD), OFC 52.5 cm (+0.8 SD), developmental age 3-3.5 years. The combination of retinoblastoma, pinealoma, and deletion of the RB1 gene diagnosed by FISH has not been reported previously. The deletion spans at least 370-420 kb in size and is predicted to include proximal and distal neighbor genes. This report may assist in establishing the clinical signs of the contiguous gene syndrome at the RB1 locus on 13q14.

Brain Neoplasms↗

PubMed2004

Proximal 11p deletion syndrome (P11pDS): additional evaluation of the clinical and molecular aspects.

The combination of multiple exostoses (EXT) and enlarged parietal foramina (foramina parietalia permagna, FPP) represent the main features of the proximal 11p deletion syndrome (P11pDS), a contiguous gene syndrome (MIM 601224) caused by an interstitial deletion on the short arm of chromosome 11. Here we present clinical aspects of two new P11pDS patients and the clinical follow-up of one patient reported in the original paper describing this syndrome. Recognised clinical signs include EXT, FPP, mental retardation, facial asymmetry, asymmetric calcification of coronary sutures, defective vision (severe myopia, nystagmus, strabismus), skeletal anomalies (small hands and feet, tapering fingers), heart defect, and anal stenosis. In addition fluorescence in situ hybridisation and molecular analysis were performed to gain further insight in potential candidate genes involved in P11pDS.

Abnormalities, Multiple↗

PubMed2004

Failure to detect DUP25 in lymphoblastoid cells derived from patients with panic disorder and control individuals representing European and American populations.

Investigation of the co-occurrence of panic and phobic disorders with joint laxity led to the identification of interstitial duplications involving human chromosome 15q24-26 (named 'DUP25') in a Spanish population. DUP25 was observed in 97% of patients and in 7% of control individuals. In the present study, we used two different methods to detect DUP25: high-throughput molecular gene dosage analysis and fluorescence in situ hybridization (FISH). We evaluated 56 lymphoblastoid cell lines derived from 26 unrelated patients with panic disorder obtained from several European and American populations and 30 normal controls. We could not find any cell line showing a result consistent with DUP25. These data do not support any association of DUP25 with panic disorder.

Adult↗

PubMed2004

Hypertrichosis, hyperkeratosis, abnormal corpus callosum, mental retardation and dysmorphic features in three unrelated females.

We report three unrelated patients with hypertrichosis, mild to moderate mental retardation, and dysmorphic facial features including low anterior hairline, thick arched eyebrows, nose with broad tip and columella below alae nasi, short philtrum, thick drooping lower lip and simple posteriorly rotated ears. They also had rough skin with hyperkeratotic plaques. Feet and finger tips were broad. All of them had personality problems like aggressiveness, stubborn temperament or tendency to withdraw. Brain MRI showed thick and short corpus callosum. We believe that these patients represent a new syndrome of unknown aetiology.

Adolescent↗

PubMed2003

Distal monosomy 18p/distal trisomy 20p--a recognizable facial phenotype?

We describe an 8.5-year-old boy with facial dysmorphism consisting of a round and flat face, telecanthus, periorbital fullness, short nose, downturned corners of the mouth, and micrognathia. In addition, profound mental retardation, tetralogy of Fallot, and renal dysplasia were present. Tentative clinical diagnoses during the 6-year follow-up included Down, Hennekam, and Noonan syndromes. Refinement of cytogenetic techniques, especially increase of banding resolution in conventional cytogenetic analysis, gave the clue to the correct diagnosis, which was proven by fluorescence in situ hybridization (FISH) with whole chromosome paints and single copy probes. We could show that he had an unbalanced translocation inherited from his father resulting in partial monosomy 18p and partial trisomy 20p. The combination of deletion 18p/duplication 20p was previously reported in three patients and seems to have a clinically recognizable face.

Child, Preschool↗

PubMed2003

Familial MCA/MR syndrome due to inherited submicroscopic translocation t(18;21)(q22.1q21.3) with breakpoint at the Down syndrome critical region.

We report three generation family that includes two patients with severe mental retardation and additional anomalies who have been studied, clinically, cytogenetically, and molecular cytogenetically. A clinical diagnosis could not be made in the propositus, but facial anomalies of Down syndrome (DS) were recognized in the maternal uncle of the propositus. In view of a strong family history of recurrent miscarriage, a familial translocation was highly suggestive. Standard cytogenetic analysis did not reveal any abnormalities. Fluorescence in situ hybridization (FISH) using subtelomeric DNA probes identified a familial cryptic translocation of chromosomes 18 and 21, resulting in partial trisomy 21 and partial monosomy 18q in both patients. FISH analysis of obligate carriers demonstrated a balanced translocation between the terminal parts of 18q and 21q. Including this family, a total of six different familial cases with cryptic or subtle subtelomeric translocations of chromosome 21q has been reported, of which three involved terminal parts of chromosome 18q. The remarkable similarity of the chromosomal breakpoints of our patients and the described families prompted us to refine the breakpoints and to discuss phenotypic differences between these patients. Our results reinforce the role of cryptic subtelomeric rearrangements in patients with mental retardation associated with physical anomalies and stress the importance of FISH technology to supplement routine cytogenetics.

Abnormalities, Multiple↗

PubMed2003

DiGeorge/velocardiofacial syndrome: FISH studies of chromosomes 22q11 and 10p14, and clinical reports on the proximal 22q11 deletion.

DiGeorge anomaly/velocardiofacial syndrome (DG/VCFS) occurs with different deletion intervals on chromosomes 22q11, while the DiGeorge anomaly (with other findings) is seen in patients with deletions of 10p14. The clinical outcome with the common 22q11 deletion (90% of cases) is well known, but the outcome with the less frequent deletion types has not been well documented. Using cytogenetic and fluorescence in situ hybridization (FISH) analysis we studied a series of 295 patients with suspected DG/VCFS. We identified 58 subjects with a 22q11 deletion, and none with a 10p deletion. Fifty-two subjects had the common deletion, five had the proximal deletion, and one had an atypical proximal deletion due to a 1;22 translocation. We report clinical data of four subjects with the proximal 22q11 microdeletion, and of one patient with the atypical proximal deletion. The anomalies observed with the proximal 22q11 microdeletion fell within the DG/VCFS spectrum. Two females, 6 and 25 years old, had normal mental development. Normal development has been reported with the common 22q11 deletion, but only in a minority of cases. This study may indicate a better intellectual and/or behavioral outcome with the proximal vs. the common 22q11 deletion, rather than a chance finding.

Abnormalities, Multiple↗

PubMed2003

Two new cases of analphoid marker chromosomes.

Supernumerary marker chromosomes (SMCs) without detectable alphoid DNA represent a rare and interesting class of rearranged marker chromosomes. These SMCs are predicted to have a neocentromere and have been referred to as neocentric marker chromosomes (NMCs). We report the molecular cytogenetic characterization of two new cases of neocentromere-containing chromosomes, one on 1q43-44 and one on 15q26. Both cases were examined using fluorescence in situ hybridization (FISH) with various alpha-satellite DNA probes, and no alphoid DNA was detected. In case 1, the NMC originated from the distal long arm of chromosome 1 by chromosomal microdissection and reverse painting. This marker lacked detectable chromosome 1q subtelomeric sequences, and therefore appeared to be a small ring chromosome. After genetic counseling with a high risk for a MCA/MR syndrome (trisomy 1q43 --> q44), the family continued the pregnancy. At age 6 months, the infant demonstrated no congenital or developmental anomalies. This is the first published example of a NMC derived from chromosome 1q. The marker may be one of the smallest, if not the smallest, human NMC reported to date. In case 2, fetal ultrasonography indicated a complex heart defect (abnormal return of lower vena cava, atrial septum malformation) and bilateral hydronephrosis. Molecular cytogenetic analysis showed an inverted duplication of the distal long arm of chromosome 15 (tetrasomy 15q24 --> qter). The pregnancy was terminated. Autopsy demonstrated polycystic left kidney and dysplastic right kidney. Case 2 represents the ninth report of a neocentromere on distal chromosome 15q, suggesting that this region may possibly especially support the formation of neocentromeres.

Adult↗

PubMed2003

Small inherited terminal duplication of 7q with hydrocephalus, cleft palate, joint contractures, and severe hypotonia.

We report a 14-month-old girl with submucous cleft palate, resolving mild hydrocephalus, severe hypotonia and joint contractures. The finding of extreme hydrocephalus, cleft palate and club feet in a fetus of the mother's previous pregnancy suggested an inherited defect. Chromosome analysis and FISH studies in the proband revealed an abnormal homolog 13 resulting in a duplication of distal chromosome 7q, 7q35-qter, and a very small associated deletion of distal chromosome 13q, 13q34-qter. The mother showed the balanced translocation. Similar clinical signs have been described with larger distal 7q duplications. Our findings suggest that 7q35-qter, and possibly the gene for sonic hedgehog (SHH) on 7q36, is the critical region for the typical facial features and the profound hypotonia observed in the 'trisomy of distal 7q' syndrome.

Abnormalities, Multiple↗

PubMed2002

Molecular cytogenetic characterization of a 10p14 deletion that includes the DGS2 region in a patient with multiple anomalies.

We report on a prenatally diagnosed four-month-old boy with DiGeorge-like phenotype and a deletion of chromosome 10pter --> 14. Fluorescence in situ hybridization (FISH) experiments using phage artificial chromosome (PAC) and yeast artificial chromosome (YAC) clones indicated that the chromosomal breakpoint was located at the proximal boundary of the DiGeorge syndrome 2 (DGS2) critical region. The patient demonstrated a high forehead, high arched eyebrows, short palpebral fissures, sparse eyelashes, prominent nose with bulbous tip, small mouth, receding chin, round ears with deficient helices, cardiac defects atrial septal defect (ASD), ventricular septal defect (VSD), mild brachytelephalangy, mild syndactyly, hypoplastic left kidney, undescended testes, muscular hypertonia, dorsally flexed big toes, and developmental delay. The phenotype corresponded well with the clinical signs of 10p deletion of this region that were described previously. The facial features appeared different from the typical face with the 22q11 deletion.

Abnormalities, Multiple↗

PubMed2002

Girl with combined cellular immunodeficiency, pancytopenia, malformations, deletion 11q23.3 --> qter, and trisomy 8q24.3 --> qter.

We describe here a 3-year-old girl demonstrating combined cellular immunodeficiency of B- and T-cells, pancytopenia, multiple anomalies, and severe mental retardation. Cytogenetic analysis and fluorescent in situ hybridization (FISH) indicated an unbalanced translocation of chromosomes 8q and 11q, resulting in monosomy 11q23.3-qter and trisomy 8q24.3-qter. The association of cellular immunodeficiency and partial deletion 11q and/or partial trisomy 8q has not been described previously; however, the 11q deletion has been reported with humoral immunodeficiency or pancytopenia. Some one-third to one-half of patients with partial monosomy 11q were reported to have pancytopenia, which has been related to the absence of the 11q23-q24 region. Our case narrows down the critical interval for thrombo- or pancytopenia to 11q23.3-q24 and excludes both the ATM (which resides on 11q23.1) and the MLL genes as possible candidate genes. We are proposing that haploinsufficiency of the NFRKB gene on 11q24-q25 and/or the ETS-1 proto-oncogene on 11q24 may have caused or contributed to the immunodeficiency (decreased levels of B- and T-lymphocytes) in our patient.

Abnormalities, Multiple↗

PubMedDate not supplied

Small reciprocal insertion detected by spectral karyotyping (SKY) and delimited by array-CGH analysis.

A 5.4-year-old male propositus is reported with mild dysmorphic features including hypoplasia of the radial part of both hands affecting thenar, thumb and fingers 2-3, incomplete syndactyly of fingers 3-4, single palmar creases, brachymesophalangia of toes 3-5, dissociated retardation of bone age, telecanthus, spina bifida occulta, cryptorchidism, muscular hypotonia, and borderline mental retardation. His karyotype was unbalanced, 46,XY,der(16)ins(4;16)(q26q28.1; q12.1q12.2)pat. In the propositus' father who had brachydactyly of fingers 2-5 and brachymesophalangia of toes 3-5 the insertion was reciprocal, 46,XY,rep ins(4;16)(q26q28.1;q12.1q12.2). Insertions are rare, reciprocal insertions most unusual. The characterization of the insertion in the propositus and the detection of its reciprocity in the father were achieved by the application of spectral karyotyping (SKY). Further examination of the propositus' unbalanced genome by array-CGH analysis delimited the chromosomal locations of the deletion/insertion rearrangement on a 0.5-2 Mb resolution level and allowed to design specific BAC FISH analyses that pinpointed the borders of the affected segments. The rearrangement involved a segment of 7.7 Mb between RP11-1030 g22 and RP11-52k8 at the chromosomal regions 4q26 and 4q28.1, respectively, and a segment of 2.8 Mb between RP11-242n20 at 16q12.1 and RP11-324d17 at 16q12.2. A simple molecular genetic explanation of the phenotype cannot be given. A relation to the Townes Brocks gene (SALL1) located 340 kb proximal of the 16q12 deletion/insertion is unlikely. Possibly more relevant is an overlap of the 16q12 deletion/insertion with a small deletion of the syntenic chromosomal region in the mouse that causes a developmental disorder of digits ("Fused toes").

Child↗

PubMedDate not supplied

A 15-year-old boy with Rubinstein-Taybi syndrome associated with severe congenital malalignment of the toenails.

Rubinstein-Taybi syndrome (RTS) is a well-known disorder characterized by growth and mental retardation, typical facial features, short stature, and broad thumbs and toes. Although several cutaneous manifestations are observed in these patients, they are not diagnostic and are usually considered to be coincidental. Congenital malalignment of the great toenails is a very rare disorder that is characterized by lateral deviation of the nail plate along its longitudinal axis. The nail plate grows into the lateral nail fold resulting in pain and infection. It is usually present at birth or begins in early childhood. We report a patient with characteristic manifestations of RTS and congenital malalignment of the great toenails. The association of these two entities has not been reported previously.

Abnormalities, Multiple↗

PubMedDate not supplied

Trisomy of 8q22.3 approximately q23-qter following an unbalanced 1;8 translocation in a boy with multiple anomalies.

An 11-month-old boy was first referred with global developmental delay, pallor and heart defects (ASD, VSD, mitral and tricuspid valve insufficiency). He also had facial abnormalities. Standard karyotyping showed additional material on one chromosome 1p homolog, and fluorescence in situ hybridization (FISH) indicated an unbalanced translocation of 1pter approximately p36.33 and 8q22.3 approximately q23. The breakpoint on p was found to reside very close to the telomere, making this a rare case of "almost pure" trisomy of 8q22.3 approximately q23-qter, without a significant partial 1p36 monosomy by FISH technique. The patient's face resembled the peculiar face in previously reported cases of 8q23-qter duplication. This report supports that critical gene(s) for cardiac septum formation reside on distal chromosome 8q.

Abnormalities, Multiple↗