ABSTRACT
INTRODUCTION: Cardiomyelic syndromes encompass congenital heart disease and skeletal malformations of the upper limbs and are related to mutations in transcription factors with T-Box domains. Holt-Oram syndrome is caused by a dominant mutation in the TBX5 gene that alters the three-dimensional structure of the protein and its DNA binding function. Several point mutations and deletions in TBX5 have been reported in patients with the Holt-Oram syndrome phenotype. PATIENTS AND METHODS: The proband was a boy with a large atrial septal defect ostium secundum type and a ventricular septal defect, diagnosed by clinical findings (heart murmur) and echocardiography. He also presented slightly hypoplastic thumbs with distal bilateral placement and an implantation index of 0.19 (compared with an average of 0.50 for his gestational age at birth). The boy was referred to the department of medical genetics to rule out 22q11.2 microdeletion syndrome. RESULTS: Karyotype and fluorescence in situ hybridization at locus D22S75 were both normal. Because of his clinical findings, molecular study for Holt-Oram syndrome was indicated, leading to the finding of a mutation at intron 7 of TBX5, probably producing a splicing alteration of the gene and resulting in a protein truncated at its C-terminal end. The proband's parents presented the wild type sequence of the gene, thus indicating that the mutation was produced de novo, although a possible germinal mosaicism in the parents could not be ruled out. CONCLUSIONS: Holt-Oram syndrome is the most frequent cause of cardiomyelic syndrome. All children with heart malformations and abnormalities of the upper limbs such as absent, hypoplastic, distally placed or triphalangic thumbs should undergo molecular studies for this syndrome.
Subject(s)
Abnormalities, Multiple/genetics , Hand Deformities, Congenital/genetics , Heart Septal Defects/genetics , T-Box Domain Proteins/genetics , Humans , Infant, Newborn , Male , MutationABSTRACT
Causes of chromosomal nondisjunction is one of the remaining unanswered questions in human genetics. In order to increase our understanding of the mechanisms underlying nondisjunction we have performed a molecular study on trisomy 8 and trisomy 8 mosaicism. We report the results on analyses of 26 probands (and parents) using 19 microsatellite DNA markers mapping along the length of chromosome 8. The 26 cases represented 20 live births, four spontaneous abortions, and two prenatal diagnoses (CVS). The results of the nondisjunction studies show that 20 cases (13 maternal, 7 paternal) were probably due to mitotic (postzygotic) duplication as reduction to homozygosity of all informative markers was observed and as no third allele was ever detected. Only two cases from spontaneous abortions were due to maternal meiotic nondisjunction. In four cases we were not able to detect the extra chromosome due to a low level of mosaicism. These results are in contrast to the common autosomal trisomies (including mosaics), where the majority of cases are due to errors in maternal meiosis.
Subject(s)
Chromosomes, Human, Pair 8 , Mosaicism , Nondisjunction, Genetic , Trisomy , Child , Child, Preschool , Female , Genomic Imprinting , Humans , Infant , Infant, Newborn , MaleABSTRACT
We report on a girl with minor anomalies and developmental delay carrying an apparently balanced paracentric inversion of chromosome 6q (q22qter). Fluorescent in situ hybridization analysis demonstrated a deletion of the subtelomeric region of 6q. This illustrates the use of specific subtelomeric fluorescent in situ hybridization probes to detect cryptic deletions as an important cause of mental retardation in seemingly balanced chromosome rearrangements.
Subject(s)
Chromosome Deletion , Chromosome Inversion , Chromosomes, Human, Pair 6/genetics , Intellectual Disability/genetics , Telomere/genetics , DNA Probes , Female , Humans , In Situ Hybridization, Fluorescence , Infant , Intellectual Disability/pathology , KaryotypingABSTRACT
A girl aged 4 years 3 months with sporadic unilateral Wilms' tumor associated with Wiedemann-Beckwith syndrome, but without aniridia, was found to have a t(X;20) in the tumor cells. Karyotypes of peripheral blood of the patient and her parents were normal. This translocation was confined to the tumor and not been previously reported either in nephroblastoma or any other neoplastic processes. Although there is no microscopic deletion on chromosome 11 and catalase activity was not decreased, we cannot rule out the possibility of a point mutation or a submicroscopic deletion.
Subject(s)
Beckwith-Wiedemann Syndrome/genetics , Chromosomes, Human, Pair 20 , Kidney Neoplasms/genetics , Translocation, Genetic , Wilms Tumor/genetics , X Chromosome , Child, Preschool , Female , Humans , KaryotypingABSTRACT
Subtelomeric rearrangements not visible by conventional cytogenetic analysis have been reported to occur in approximately 5% of patients with unexplained mental retardation (MR). As the prevalence of MR is high, many patients need to be screened for these chromosomal abnormalities routinely. Multiplex ligation-dependent probe amplification (MLPA) is a new technique for measuring sequence dosage, allowing large number of samples to be processed simultaneously and thus significantly reducing laboratory work. We have assessed its performance for the detection of subtelomeric rearrangements by comparing the results with those of our previous multiprobe fluorescence in situ hybridization (FISH) assay. We have tested 50 patients with idiopathic MR, dysmorphic features, congenital malformations, and/or familial history of MR. Our results show a high degree of concordance between the two techniques for the 50 samples tested. On the basis of these results, we conclude that MLPA is a rapid, accurate, reliable, and cost-effective alternative to FISH for the screening of subtelomeric rearrangements in patients with idiopathic MR.
Subject(s)
Chromosome Aberrations , In Situ Hybridization, Fluorescence/methods , Intellectual Disability/genetics , Ligase Chain Reaction/methods , Female , Genetic Testing/methods , Humans , Male , Microsatellite Repeats , Telomere/geneticsABSTRACT
BACKGROUND: Euchromatic imbalances at the cytogenetic level are usually associated with phenotypic consequences. Among the exceptions are euchromatic variants of chromosome 16 (16p+) with normal phenotype. There is a growing list of euchromatic duplications and deletions involving both G-positive and G-negative bands that seem to be phenotypically neutral, but these euchromatic variants are rare. OBJECTIVE: The aim of this report is to describe a new familial case of euchromatic variant 16p+ and to emphasise the misinterpretation of these rare euchromatic variants particularly when ascertained at prenatal diagnosis. METHODS AND RESULTS: Fluorescence in situ hybridisation with clone RP11-261A7 showed an amplified signal in the larger chromosome 16. This clone contains FLJ43855 gene, similar to sodium- and chloride-dependent creatine transporter. CONCLUSION: So, this 16p+ variant that involves amplification of pseudogenetic sequences is considered a polymorphism in normal individuals.
Subject(s)
Chromosome Disorders/diagnosis , Chromosome Disorders/embryology , Chromosomes, Human, Pair 16 , Euchromatin , Prenatal Diagnosis/methods , Adult , Chromosome Aberrations/embryology , Euchromatin/isolation & purification , Female , Humans , In Situ Hybridization, Fluorescence/methods , PregnancyABSTRACT
The 22q11.2 deletion syndrome is commonly diagnosed using fluorescence in situ hybridization (FISH) with commercial probes. The chromosomal breakpoints and deletion size are subsequently characterized by short tandem repeat (STR) segregation tests or by further FISH probes. Recently, a multiplex ligation-dependent probe amplification (MLPA) single tube assay was developed to detect deletions of the 22q11.2 region and other chromosomal regions associated with DiGeorge/velocardiofacial syndrome. We have compared the results of these three techniques in a group of 30 patients affected with 22q11.2 deletion syndrome. MLPA correctly called all patients who had been previously diagnosed by FISH. The MLPA results were concordant in all patients with the STR analysis in respect to deletion size. Furthermore, this novel technique resolved seven cases that were undetermined by STR analysis. These results confirm the efficiency of MLPA as a rapid, reliable, economical, high-throughput method for the diagnosis of 22q11.2 deletion syndrome.
Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 22 , In Situ Hybridization, Fluorescence , Molecular Probe Techniques , Nucleic Acid Amplification Techniques , Tandem Repeat Sequences , DiGeorge Syndrome/genetics , Humans , In Situ Hybridization, Fluorescence/methods , Karyotyping/methods , Nucleic Acid Amplification Techniques/methods , Syndrome , Velopharyngeal Insufficiency/geneticsABSTRACT
A child with a facial dysmorphy and congenital malformations, showed in the chromosome analysis a partial trisomy of chromosome 20. This anomaly, resulted from a maternal translocation t(11;20), (q35;q11).
Subject(s)
Chromosomes, Human, 19-20 , Trisomy , Abnormalities, Multiple/genetics , Humans , Infant, Newborn , Male , Translocation, GeneticABSTRACT
Two infants with complete trisomy of chromosome 9 are described. One patient, died a few minutes after birth and another survived 24 hours. The main clinical findings in this syndrome are: intrauterine growth retardation, characteristic facial dysmorphism, hypoplastic external genitalia and malformations of heart, brain and skeleton.
Subject(s)
Abnormalities, Multiple/genetics , Chromosomes, Human, 6-12 and X , Trisomy , Face/abnormalities , Female , Fetal Growth Retardation/genetics , Genitalia/abnormalities , Humans , Infant, Newborn , Karyotyping , Male , PregnancyABSTRACT
Six males, four adults and two children, with very important mental deficiency and speech disturbances, belonging to two families are presented. The six patients show the clinical peculiarities of the "X-linked mental retardation, macroorchidism, and the Xq27 fragile site", but the chromosomal alteration only was presented in five cases. Patient who did not have the chromosomal defect presented the same IQ than his brothers, but he had a less severe macroorchidism, a better speech and more normal clinical features. One of the patients shows a shorter arm which linkage with the syndrome is discussed.
Subject(s)
Fragile X Syndrome/genetics , Intellectual Disability/genetics , Sex Chromosome Aberrations/genetics , Testicular Diseases/genetics , Adolescent , Adult , Child , Female , Humans , Karyotyping , Male , Organ Size , Pedigree , Speech Disorders/genetics , Testis/pathology , X Chromosome/ultrastructureABSTRACT
A three month old male with Down's Syndrome is presented. Cytogenetic studies reveal a count of 46 chromosomes with a G/G "tandem" translocation. New staining techniques show the marker chromosome closed at both ends and with two symmetrical bands.
Subject(s)
Chromosome Aberrations , Chromosomes, Human, 21-22 and Y , Down Syndrome/genetics , Humans , Infant , Karyotyping , Male , Translocation, GeneticABSTRACT
We report a child with facial dysmorphic features, hypoplasia of the external genitalia, intestinal malrotation, congenital cardiac defect, and minor limb anomalies. Chromosome studies showed a recombinant chromosome 7, rec(7) dup p, resulting from a maternal pericentric inversion inv(7)(p15 q36). Thus, this child had partial trisomy 7p in addition to a small distal monosomy 7. The clinical findings are compared with those found in previous reports of trisomy 7p. Finally, some general principles for genetic counselling are discussed.
Subject(s)
Abnormalities, Multiple/genetics , Chromosome Inversion , Chromosomes, Human, Pair 7 , Recombination, Genetic , Chromosome Banding , Genetic Counseling , Humans , Infant, Newborn , Male , Monosomy , Risk Factors , TrisomyABSTRACT
Authors have had the opportunity to study a patient affected by a malformative syndrome with severe motricity and mental retardation. Physical findings (namely: spacious forehead, flat and round face, small palpebral fissures, hypotonicity and growth retardation) are similar to the phenotype previously described in trisomy 10q. Chromosomal diagnosis failed until G, Q and R banding technique was applied. With this technique a partial 10q trisomy (q24 leads to q ter) due to a maternal translocation t(6:10)(q26;q24) was found.
Subject(s)
Abnormalities, Multiple/genetics , Chromosome Aberrations/genetics , Chromosomes, Human, 6-12 and X/ultrastructure , Translocation, Genetic , Trisomy , Chromosome Disorders , Dwarfism/genetics , Female , Humans , Infant , Intellectual Disability/genetics , Karyotyping , Pedigree , PhenotypeABSTRACT
This report describes an azoospermic male carrying a Y/autosome translocation. The patient had a 46,X,t(Y;10)(q12;p13) chromosome complement in a lymphocyte culture. The cytogenetic study of this patient is described, together with testicular histology, spermiogram, hormone levels, and clinical history.
Subject(s)
Chromosomes, Human, 6-12 and X , Oligospermia/genetics , Sex Chromosomes , Translocation, Genetic , Y Chromosome , Adult , Chromosome Banding , Humans , Male , Phenotype , Testis/anatomy & histologyABSTRACT
A fourteen years old girl, with short height and primary amenorrhea is presented. Laparoscopic examination revealed bilateral gonadal streaks. Chromosome analysis from leukocyte culture, revealed mosaicism with a predominant cell line del 45,X and another cell lines del 46,XXX/46,X,r(X)46,X,del(X)/47,XX,r(X)47,XXdel(X)/48,XXXX.
Subject(s)
Mosaicism , Turner Syndrome/diagnosis , Adolescent , Dermatoglyphics , Female , Humans , KaryotypingABSTRACT
A dysmorphic female born with partial trisomy of the proximal segment of the long arm of chromosome 14 had 47 chromosomes. The extra one was acrocentric, smaller than the D group, and bigger than the G-chromosome group. By GTG banding it was identified as a deleted chromosome 14, the karyotype being 47,XX,+del 14(q24). Chromosome analysis of the parents was normal.
Subject(s)
Abnormalities, Multiple/genetics , Chromosomes, Human, 13-15 , Trisomy , Chromosome Banding , Female , Humans , Infant , Karyotyping , PhenotypeABSTRACT
This paper describes a case of Klinefelter's syndrome with 48,XXYY. Patient had mental retardation and dysmorfic face. Although mental retardation may be recognized early in life, it is difficult to establish a clinical diagnosis of Klinefelter's syndrome before puberty when small testes, gynecomastia and other phisical stigmata may become apparent.
Subject(s)
Klinefelter Syndrome/diagnosis , Child , Dermatoglyphics , Humans , Karyotyping , MaleABSTRACT
A case of Dyschondrosteosis associated with Turner's syndrome is presented. There is no evidence of an autosomal dominant inheritance. The patient shows the typical clinical and radiological aspects of this disease, with severe intensity. Mental retardation is also important.
Subject(s)
Osteochondrodysplasias/complications , Turner Syndrome/complications , Female , Humans , KaryotypingABSTRACT
A two month old boy with multiple malformations: mental retardation, microcephaly, hyperterloism, displasic ears, hypospadias, unilateral cryptorchidism and holoprosencephaly is presented. In leukocytes culture, patient shows a deletion of the short arm of a 18 chromosome. This aberration apears "de novo" in this patient.
Subject(s)
Abnormalities, Multiple/genetics , Chromosome Aberrations , Chromosome Deletion , Humans , Infant , Karyotyping , MaleABSTRACT
Authors present a new case with partial trisomy for long arms of chromosome 18(q12-qter) resulting from a balanced translocation t(4;18) on her mother. Comparing clinical features of our patient with that of other reported cases with the same trisomic segment, we can deduce that most important characteristics on this syndrome are: psychomotor and grow retardation, congenital heart disease, dolicocephaly, low set and malformed ears, micrognathia, short neck with redundant skin and a longer survival than in total trisomy 18.