Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a liveborn infant with uniparental disomy (UPD) with trisomy 15 mosaicism. Third trimester amniocentesis yielded a 46,XX/47,XX,+15 karyotype. Symmetrical growth retardation, distinct craniofacies, congenital heart disease, severe hypotonia and minor skeletal anomalies were noted. The infant died at 6 weeks of life. Peripheral lymphocyte chromosomes were "normal" 46,XX in 100 cells. Parental lymphocyte chromosomes were normal. Skin biopsy showed 47,XX,+15 in 80% of fibroblasts and results were equivalent in fibroblasts from autopsy lung tissue. Molecular analysis revealed maternal uniparental heterodisomy for chromosome 15 in the 46,XX cell line. We describe an emerging phenotype of trisomy 15 mosaicism, confirm that more than one tissue should be studied in all cases of suspected mosaicism, and suggest that UPD be considered in all such cases.
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PMID:Trisomy 15 mosaicism and uniparental disomy (UPD) in a liveborn infant. 874 73

Prader-Willi syndrome is characterized by hypotonia and feeding difficulties in the neonatal period, with the childhood development of hyperphagia leading to obesity, developmental delay, hypogonadism, short stature and small hands and feet. Correct diagnosis of Prader-Willi syndrome is important because of its clinical implications and the need for family genetic counseling. In order to determine the most efficient method of diagnosing the condition, we evaluated 37 patients with a putative diagnosis of Prader-Willi syndrome by both clinical and molecular cytogenetic analyses. Clinical evaluation showed that 25 patients fulfilled the diagnostic criteria for Prader-Willi syndrome. A deletion of the region 15q11.2-13 was cytogenetically identified in 20 patients using a high-resolution technique. Four additional cases were detected by fluorescence in situ hybridization (FISH) with the cosmid probes for D15S11, r-aminobutyric acid receptor beta 3 (GABRB3), small nuclear ribonucleoprotein-associated peptide N (SNRPN) or D15S10 (Prader-Willi/ Angelman syndrome region probes). The deletion of SNRPN was documented in 24 Prader-Willi syndrome patients. Only one additional patient with typical Prader-Willi syndrome features did not have any deletion over 15q11-13 at either the cytogenetic or molecular level. FISH provides a more reliable method than high-resolution chromosome analysis for the diagnosis of Prader-Willi syndrome. Associated conditions such as hypopigmentation, small-joint laxity, arachnodactyly, seizure disorder, optic atrophy, congenital heart disease, Perthes' disease, hirsutism, astigmatism/amblyopia, microcephaly and neuropsychiatric disturbances dictate the effects of a contiguous gene syndrome. Morbidity is high among patients with obesity and associated conditions. Appropriate genetic counseling should be given to the parents and dietary management should be helpful for patients with Prader-Willi syndrome.
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PMID:Prader-Willi syndrome: clinical and molecular cytogenetic investigations. 877 55

Mosaic trisomy 14 in liveborns is rare and may be accompanied by uniparental disomy in the euploid cell line. We report the case of a 6 month old male with growth failure, microcephaly, macroglossia, developmental delay, hypotonia, congenital heart disease, neonatal hepatitis, cryptorchidism, talipes equinovarus, limb length asymmetry, bilateral overriding of 1st by 2nd toe, and extended abnormal pigmentation in a linear-whorl distribution. The proband's karyotype in peripheral lymphocytes and skin fibroblasts was mos47,XY,+14/46,XY. Parental blood chromosomes were normal. Molecular analysis excluded uniparental disomy in the euploid cell line of the proband.
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PMID:Mosaic trisomy 14 with hepatic involvement. 925 57

The main manifestations of neuromuscular disease in the newborn period are hypotonia and weakness. Infants with severe hypotonia but only marginal weakness usually do not have a disorder of the lower motor unit. These infants may have genetic conditions, metabolic disturbances, congenital heart disease, hypothyroidism, sepsis, or other systemic disorders. Early on, neonates with central nervous system pathology may present with profound hypotonia, decreased reflexes, and moderate to severe but transient weakness. However, they also tend to have seizures, obtundation, cranial nerve signs, or history of perinatal asphyxia.
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PMID:Neuromuscular disorders in the newborn. 939 65

We have isolated, mapped and sequenced the 5' promoter region of the human SH3BGR (SH3-Binding Glutamine Rich) gene located in the Down syndrome region-2, between markers D21S55 and MX1 of human chromosome 21. This region has been postulated as the minimal region for congenital heart disease and 6 facial and dermatoglyphic features present in Down syndrome. The SH3BGR gene is expressed in fetal and adult heart and in skeletal muscle and therefore it is a candidate gene for the congenital heart defect and muscle hypotonia. The 5' region of the gene has been positioned in a 115 kb PAC/cosmid contig with full EcoRI/SmaI restriction map covering cosmid pockets 122-123 as well as cosmid pocket 124 located between markers D21S268 and D21S220. Sequencing of the SH3BGR promoter region has allowed the identification of several potential regulatory elements of this candidate gene for the congenital heart disease and other potential DS features. Several of the elements identified are also present in other muscle-expressed genes.
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PMID:High-resolution physical map and identification of potentially regulatory sequences of the human SH3BGR located in the Down syndrome chromosomal region. 942 70

We report a 34-year-old female with a de novo balanced reciprocal translocation involving 2q37.2 and 7q36.3. She has a unique combination of multiple congenital malformations that include redundant skin, complete tissue syndactyly of the hands and feet, hirsutism, polycystic ovaries and bilateral anterior chamber eye anomalies. Her son has inherited the unbalanced product (46,XY,der(2) t(2;7)(q37.2;q36.3). He has a similar clinical picture with additional features including complex congenital heart disease, post axial polydactyly, hypotonia and global developmental delay. The breakpoints may indicate the location of the gene(s) responsible for this unique combination of features.
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PMID:Anterior chamber eye anomalies, redundant skin and syndactyly--a new syndrome associated with breakpoints at 2q37.2 and 7q36.3. 1045 47

We observed a novel 3.5 Mb 5q subtelomeric deletion in a 3-year-old girl with developmental delay, hypotonia and multiple minor anomalies. Comparison of her phenotype with the few published patients with terminal 5q35 deletions revealed several overlapping features, but also showed remarkable differences such as shortness of stature versus macrosomia. After the report of 5q35.3 microdeletions in Sotos syndrome we integrated the published BACs into the public draft sequence and exactly mapped the deletion size in our patient by FISH analysis with 15 BAC probes. We demonstrated that the deletion in our patient is immediately adjacent to the reported Sotos syndrome deletion site. Subtracting the symptoms of Sotos syndrome from the published patients with larger 5q35.3 deletions allowed us to delineate a distinct phenotype of prenatal lymphedema with increased nuchal translucency, pronounced muscular hypotonia and delay of reaching motor milestones, but speech development within normal limits, wide fontanels, failure to thrive with postnatal short stature, and multiple minor anomalies such as mildly bell-shaped chest, minor congenital heart disease, and a distinct facial gestalt, associated with the novel 3.5 Mb cryptic deletion. We further showed in our patient that the deletion of the LCT(4) synthase gene results in a reduction of cysteinyl leukotriene synthesis to about 65% compared to normal values. The prenatal nuchal lymphedema associated with this deletion syndrome my be related to the deletion of the FLT4 gene causing autosomal dominant primary lymphedema and contributes to the differential diagnosis of increased fetal nuchal translucency.
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PMID:A novel 5q35.3 subtelomeric deletion syndrome. 1290 Aug 93

We report on a patient with a full monosomy 21 (FM21) prenatally diagnosed in cord fetal blood, and subsequently confirmed in other tissues. Subtle chromosomal translocations of chromosome 21, were ruled-out by FISH using both painting and 21q telomeric probes. Microsatellites analysis demonstrated the paternal origin of the single chromosome. The propositus showed at 32 weeks of gestation a severe intrauterine growth retardation and microcephaly. He was born with multiple congenital malformations, hypotonia, microcephaly, bilateral microphthalmia (more severe on the left), facial dysmorphism, agenesis of the external auditory meatus, redundant skin in the neck, narrow chest, flat scrotum, cryptorchydism, hypospadias, micropene, camptodactyly, nail hypoplasia, and abnormal palmar and plantar creases. The patient died in the first day of life. At necropsy, micrencephaly, semilobar holoprosencephaly, polimicrogyria, ocular abnormalities, skeletal anomalies, congenital heart disease, and agenesis of right kidney were also observed. To our best knowledge, this case is one of the most completely patient studied with FM21.
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PMID:A prenatally diagnosed patient with full monosomy 21: ultrasound, cytogenetic, clinical, molecular, and necropsy findings. 1510 21

The Snail-related zinc-finger transcription factor, SLUG (SNAI2), is critical for the normal development of neural crest-derived cells and loss-of-function SLUG mutations have been proven to cause piebaldism and Waardenburg syndrome type 2 in a dose-dependent fashion. However, little is known about the consequences of SLUG overexpression in embryonic development. We report SLUG duplication in a child with a unique de novo 8q11.2-->q13.3 duplication associated with tetralogy of Fallot, submucous cleft palate, renal anomalies, hypotonia and developmental delay. To investigate the effects of Slug overexpression on development, we analyzed mice carrying a Slug transgene. These mice were morphologically normal at birth, inferring that Slug overexpression is not sufficient to cause overt morphogenetic defects. In the adult mice, there was a 20% incidence of sudden death, cardiomegaly and cardiac failure associated with incipient mesenchymal tumorigenesis. These findings, while not directly implicating Slug in congenital and acquired heart disease, raise the possibility that Slug overexpression may contribute to specific cardiac phenotypes and cancer development.
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PMID:SLUG (SNAI2) overexpression in embryonic development. 1671 46

FG syndrome was originally described as a rare syndromic cause of X-linked mental retardation associated with congenital heart disease, anal atresia, inguinal hernia, cryptorchidism, and other anomalies. However, recent reports have highlighted the more common milder presentation which has for cardinal features developmental delay, particularly in speech, neonatal hypotonia, relative macrocephaly, dysmorphic facial features, severe constipation, and few if any congenital malformations. Thus far, five separate loci have been identified on the X chromosome but attempts at finding the responsible gene have not yet been successful. Given that one putative FG locus (FGS2) is situated at Xq28, which is the location of the Filamin A gene (FLNA), and that a Filamin A mutation was reported in a boy with facial dysmorphism and constipation, it was hypothesized that Filamin A mutations could be one cause of FG syndrome. Indeed, a previously unreported FLNA missense mutation (P1291L) was detected in our patient with FG syndrome, thus supporting this hypothesis and indicating that FG syndrome could now be added to the list of Filamin A-related disorders. Filamin A studies in other children with FG syndrome would help to confirm this association.
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PMID:Filamin A mutation is one cause of FG syndrome. 1763 75


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