Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Publication year range
1.
Am J Med Genet A ; 194(4): e63476, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37974505

ABSTRACT

Cat Eye Syndrome (CES) is a rare genetic disease caused by the presence of a small supernumerary marker chromosome derived from chromosome 22, which results in a partial tetrasomy of 22p-22q11.21. CES is classically defined by association of iris coloboma, anal atresia, and preauricular tags or pits, with high clinical and genetic heterogeneity. We conducted an international retrospective study of patients carrying genomic gain in the 22q11.21 chromosomal region upstream from LCR22-A identified using FISH, MLPA, and/or array-CGH. We report a cohort of 43 CES cases. We highlight that the clinical triad represents no more than 50% of cases. However, only 16% of CES patients presented with the three signs of the triad and 9% not present any of these three signs. We also highlight the importance of other impairments: cardiac anomalies are one of the major signs of CES (51% of cases), and high frequency of intellectual disability (47%). Ocular motility defects (45%), abdominal malformations (44%), ophthalmologic malformations (35%), and genitourinary tract defects (32%) are other frequent clinical features. We observed that sSMC is the most frequent chromosomal anomaly (91%) and we highlight the high prevalence of mosaic cases (40%) and the unexpectedly high prevalence of parental transmission of sSMC (23%). Most often, the transmitting parent has mild or absent features and carries the mosaic marker at a very low rate (<10%). These data allow us to better delineate the clinical phenotype associated with CES, which must be taken into account in the cytogenetic testing for this syndrome. These findings draw attention to the need for genetic counseling and the risk of recurrence.


Subject(s)
Aneuploidy , Chromosome Disorders , Chromosomes, Human, Pair 22 , Eye Abnormalities , Heart Defects, Congenital , Humans , Retrospective Studies , In Situ Hybridization, Fluorescence , Chromosomes, Human, Pair 22/genetics , Heart Defects, Congenital/genetics
2.
Prenat Diagn ; 34(2): 185-91, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24222400

ABSTRACT

OBJECTIVE: The objective of this study is to validate the diagnostic accuracy of a non-invasive prenatal test for detecting trisomies 13, 18, and 21 for a population in Germany and Switzerland. METHODS: Random massively parallel sequencing was applied using Illumina sequencing platform HiSeq2000. Fetal aneuploidies were identified using a median absolute deviation based z-score equation. A bioinformatics algorithm based on guanine-cytosine normalization was applied after the data were unblinded. Results of massively parallel sequencing and invasive procedures were compared. RESULTS: Overall, 40/42 samples were correctly classified as trisomy 21-positive, including a translocation trisomy 21 [46,XY,der(13;21),+21] and a structural aberration of chromosome 21 [46,XX,rec(21)dup(21q)inv(21)(p12q21.1)] but not including a low percentage mosaic trisomy 21 [47,XY,+21/46,XY], [sensitivity: 95.2%; one-sided lower confidence limit: 85.8%]; 430/430 samples were correctly classified as trisomy 21-negative (specificity: 100%; one-sided lower CL: 99.3%). Using a new bioinformatics algorithm with guanine-cytosine normalization, detection of trisomy 21 was facilitated, and five of five trisomy 13 cases and eight of eight trisomy 18 cases were correctly identified. CONCLUSION: Our newly established non-invasive prenatal test allows detection of fetal trisomies 13, 18, and 21 with high accuracy in a population in Germany and Switzerland.


Subject(s)
Chromosome Disorders/diagnosis , Down Syndrome/diagnosis , High-Throughput Nucleotide Sequencing , Prenatal Diagnosis , Sequence Analysis, DNA , Trisomy/diagnosis , Adult , Algorithms , Amniocentesis , Aneuploidy , Chorionic Villi Sampling , Chromosome Aberrations , Chromosome Disorders/genetics , Chromosomes, Human, Pair 13/genetics , Chromosomes, Human, Pair 18/genetics , Down Syndrome/genetics , Female , Germany , Humans , Karyotyping , Male , Middle Aged , Mosaicism , Pregnancy , Sensitivity and Specificity , Switzerland , Trisomy/genetics , Trisomy 13 Syndrome , Trisomy 18 Syndrome , Young Adult
3.
J Pediatr ; 161(5): 933-42, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22683032

ABSTRACT

OBJECTIVE: To determine the contribution of submicroscopic chromosomal imbalances to the etiology of Silver-Russell syndrome (SRS) and SRS-like phenotypes. STUDY DESIGN: We performed molecular karyotyping in 41 patients with SRS or SRS-like features without known chromosome 7 and 11 defects using the Affymetrix SNP Array 6.0 system (Affymetrix, High Wycombe, United Kingdom). RESULTS: In 8 patients, pathogenic copy number variations with sizes ranging from 672 kb to 9.158 Mb were identified. The deletions in 1q21, 15q26, 17p13, and 22q11 were associated with known microdeletion syndromes with overlapping features with SRS. The duplications in 22q13 and Xq25q27 represent unique novel copy number variations but have an obvious influence on the phenotype. In 5 additional patients, the pathogenetic relevance of the detected variants remained unclear. CONCLUSION: Pathogenic submicroscopic imbalances were detectable in a significant proportion of patients with short stature and features reminiscent of SRS. Therefore, molecular karyotyping should be implemented in routine diagnostics for growth-retarded patients with even slight dysmorphisms suggestive for SRS.


Subject(s)
Growth Disorders/diagnosis , Karyotyping/methods , Silver-Russell Syndrome/diagnosis , Silver-Russell Syndrome/genetics , Child , Child, Preschool , Chromosome Aberrations , Chromosome Deletion , Chromosomes, Human, Pair 11/genetics , Chromosomes, Human, Pair 7/genetics , Female , Genetic Markers/genetics , Growth Disorders/genetics , Humans , Infant , Male , Mutation , Oligonucleotide Array Sequence Analysis , Phenotype , Polymorphism, Single Nucleotide
4.
Clin Lab ; 56(9-10): 501-4, 2010.
Article in German | MEDLINE | ID: mdl-21090067

ABSTRACT

Whereas in the 18th century medical science was influenced by both religion and the humanities, this changed around the middle of the 19th century as applied science accompanied a rapid development in medicine, especially in the fields of physiology and pathology. Currently the principles of biology, chemistry, and physics form the basis of scientifically-based medicine. This becomes even more evident when looking at the distribution of Nobel laureates for medicine and physiology in the first decade of the new millennium, namely 18 natural scientists compared with only 8 medical practitioners (see www.bnld.eu). In Germany, cooperation between medical practitioners and natural scientists is often hindered by legislation as well as professional claims. Whereas some procedures are restricted to medical practitioners, others, such as diagnostic testing, can be delegated to and performed by natural scientists, although here legal confirmation may be lacking in some cases, for example in genetics. Such discrimination often hinders potential cooperation and can no longer be seen as up to date. Whereas evidence based medicine forms the basis of individual treatment for patients, the introduction of disease management programmes by hospital administrators nullifies any positive effects of evidence-based medicine and reduces the patient to a cost-factor statistic. The aim of present government policy is a cost-effective treatment of diseases, often at the cost of the patient. Medicine is changing from an empirically-based therapy to a rationalised, molecular science. Parity between natural scientists and medical practitioners at all relevant levels is an indispensible prerequisite for a beneficial future healthcare programme. New, as well as existing professions for natural scientists in healthcare must be defined clearly and must have a legal basis, the point of view of the bnld (Berufsvereinigung der Naturwissenschaftler in der Labordiagnostik) for many years.


Subject(s)
Medicine/trends , Natural Science Disciplines/trends , Evidence-Based Medicine/standards , Germany , Humans , Legislation, Medical
SELECTION OF CITATIONS
SEARCH DETAIL
...