Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glycerol kinase deficiency occurs either as a relatively benign isolated enzyme deficiency, or as part of a syndrome resulting from a microdeletion in the p21 region of the X chromosome associated with congenital adrenal hypoplasia and/or Duchenne muscular dystrophy. Developmental delay is a consistent feature of the microdeletion syndrome but not of the isolated enzyme defect. We report a case of isolated glycerol kinase deficiency in a neonate presenting with hypotonia, apnea, mild developmental delay, and glyceroluria, without evidence of adrenal insufficiency or myopathy. A mild communicating hydrocephalus was noted on magnetic resonance imaging brain scan. It is important, therefore, to exclude glyceroluria in infants being investigated for apnea and hypotonia.
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PMID:Isolated glycerol kinase deficiency in a neonate. 751 7

We report on 2 girls with mosaic tetrasomy 8p. Patient 1 showed the extra iso 8p chromosome in 20% of cultured lymphocytes and 18% of cultured fibroblasts [46,XX/47,XX,+i(8p)]. She presented with growth retardation, mild facial alterations, and motor developmental delay. Patient 2 presented with developmental delay, hypotonia, and slight facial alterations; she had the extra iso 8p chromosome in 94% of cultured peripheral lymphocytes. The patients are compared to the 6 previously reported cases. In our experience, the presently reported patients clinically resemble children with inv dup(8)(p21-p22) and patients with mosaic trisomy 8.
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PMID:Mosaic tetrasomy 8p in two patients: clinical data and review of the literature. 751 21

A genetics evaluation was requested for a 6-week-old infant with multiple congenital malformations including mild craniofacial anomalies, truncal hypotonia, hypospadias, and a ventriculoseptal defect. Blood obtained for chromosome analysis revealed an abnormal chromosome 4. Paternal chromosome analysis showed a 46,XY, inv ins (3;4)(p21.32;q25q21.2), inv(4)(p15.3q21.2) karyotype. Therefore, the proband's chromosome 4 was the unbalanced product of this insertional translocation from the father resulting in partial monosomy 4q. Additionally, the derivative 4 had a pericentric inversion which was also seen in the father's chromosome 4. During genetic counseling, the proband's 2-year-old brother was evaluated. He was not felt to be abnormal in appearance, but was described as having impulsive behavior. Chromosome analysis on this child revealed 46,XY,der(3)inv ins(3;4)(p21.32;q25q21.2)pat. This karyotype results in partial trisomy 4q. FISH using two-color "painting" probes for chromosomes 3 and 4 confirmed the G-banded interpretation in this family. The segregation seen in this family resulted in both reciprocal products being observed in the two children, with partial 4q monosomy showing multiple congenital anomalies, and partial 4q trisomy showing very few phenotypic abnormalities.
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PMID:Segregation of a paternal insertional translocation results in partial 4q monosomy or 4q trisomy in two siblings. 874 10

We describe a 1-year-old boy with mental and physical retardation, a large anterior fontanel, brachycephaly with flat occiput, short and stubby fingers, generalized hypotonia, ocular hypertelorism, low-nasal bridge, long philtrum, high-narrow palate, apparently low-set ears, and a small mandible. Cytogenetic analysis utilizing high resolution chromosome banding technique showed an unbalanced karyotype consisting of 46,XY,add(21)(q22.3) that originated from maternal balanced translocation between chromosomes 7 and 21. Fluorescence in situ hybridization (FISH) using micro-dissected library probe pool from chromosome 7 confirmed the additional material on 21q was derived from chromosome 7. Our results indicated that the patient had an unbalanced translocation, 46,XY, der(21)t(7;21)(p21.2;q22.3)mat, which resulted in duplication for distal 7p. Our patient is similar to reported cases with a 7p15-->pter or larger duplication of 7p, suggesting that the critical segment causing the characteristic phenotype of 7p duplication syndrome, including large anterior fontanel, exists at 7p21.2 or 7p21.2-->pter.
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PMID:Duplication of 7p21.2-->pter due to maternal 7p;21q translocation: implications for critical segment assignment in the 7p duplication syndrome. 1049 83

A derivative chromosome 8 was observed in a newborn boy who presented with low birth weight, multiple congenital anomalies, and dysmorphic face. The der(8) was further characterized at age 18 months by a high resolution G-banding analysis, spectral karyotyping, and fluorescence in situ hybridization (FISH) with multiple DNA probes. The karyotype was described as 46,XY,der(8)(qter-->q24.13::p21.3-->p23.3::p23.3-->qter), representing an inverted duplication of region 8p21.3-->p23.3 and a duplication of region 8q24.13-->qter, which attaches to the duplicated short arm segment at 8p21.3. Different from previously reported patients with an inverted duplication (8p), no deletion was detected in the distal region of 8p in this case. This young child had manifested a broad nasal bridge, micrognathia, cleft lip, hydrocephalus, partial agenesis of the corpus callosum, Dandy-Walker malformation, congenital heart defects, dysplastic kidneys, hydronephrosis, marked hypotonia, and significant psychomotor retardation. These features are compared with those commonly seen in cases with an inverted duplication of 8p and cases with a partial trisomy of 8q.
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PMID:Molecular cytogenetic characterization of a derivative chromosome 8 with an inverted duplication of 8p21.3-->p23.3 and a rearranged duplication of 8q24.13-->qter. 1290 Sep 8

A male patient with profound mental retardation, athetosis, nystagmus, and severe congenital hypotonia (Duchenne muscular dystrophy [DMD]) was previously shown to carry a pericentric inversion of the X chromosome, 46,Y,inv(X)(p21.2q22.2). His mother carried this inversion on one X allele. The patient's condition was originally misdiagnosed as cerebral palsy, and only later was it diagnosed as DMD. Because the DMD gene is located at Xp21.2, which is one breakpoint of the inv(X), and because its defects are rarely associated with severe mental retardation, the other clinical features of this patient were deemed likely to be associated with the opposite breakpoint at Xq22. Our precise molecular-cytogenetic characterization of both breakpoints revealed three catastrophic genetic events that had probably influenced neuromuscular and cognitive development: deletion of part of the DMD gene at Xp21.2, duplication of the human proteolipid protein gene (PLP) at Xq22.2, and disruption of a novel gene. The latter sequence, showing a high degree of homology to the Sec4 gene of yeast, encoded a putative small guanine-protein, Ras-like GTPase that we have termed "RLGP." Immunocytochemistry located RLGP at mitochondria. We speculate that disruption of RLGP was responsible for the patient's profound mental retardation.
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PMID:The Xq22 inversion breakpoint interrupted a novel Ras-like GTPase gene in a patient with Duchenne muscular dystrophy and profound mental retardation. 1214 44

An 8-year-old boy presenting with hypotonia, moderate mental retardation, developmental delay, and psychomotor retardation is reported. Magnetic resonance imaging of the brain at age 3 years revealed a Dandy-Walker variant. Cytogenetic analysis of the peripheral blood revealed a derivative chromosome 12 with unknown additional material attached to the distal region of the long arm of chromosome 12. The parental karyotypes were normal. Spectral karyotyping (SKY) using the 24-color SKY probes and fluorescence in situ hybridization (FISH) using the specific 7p, 7q, 12p, and 12q telomeric probes confirmed a duplication of distal 7p and a deletion of terminal 12q. The karyotype of the proband was designated as 46,XY.ish der(12)t(7;12) (p21.2;q24. 33)(SKY+, 7pTEL+, 12qTEL-). The present case provides evidence for the association of partial trisomy 7p (7p21.2-->pter) and partial monosomy 12q (12q24.33-->qter) with a cerebellar malformation and the usefulness of SKY and FISH in the identification of a de novo aberrant chromosome resulting from an unbalanced translocation.
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PMID:Spectral karyotyping and fluorescence in situ hybridization analysis of de novo partial trisomy 7p (7p21.2-->pter) and partial monosomy 12q (12q24.33-->qter). 1671 78

Translocations involving the short arms of the X and Y chromosomes are rare and can result in a functional disomy of the short arm of the X chromosome, including the dosage-sensitive sex reversal (DSS) locus. A result of such imbalance may be sex reversal with multiple congenital anomalies. We present the clinical and cytogenetic evaluation of a newborn infant with DSS and additional clinical findings of minor facial anomalies, left abdominal mass, 5th finger clinodactyly, and mild hypotonia. The external genitalia appeared to be normal female. The infant had bilateral corneal opacities and findings suggestive of anterior segment dysgenesis. Ultrasonography showed a small uterus with undetectable ovaries, and a left multicystic dysplastic kidney. High-resolution chromosome analysis identified the presence of a derivative Y chromosome, 47,XY, +der(Y)t(X;Y)(p21.1;p11.2), which was confirmed by fluorescence in situ hybridization studies. Array CGH showed a 35.1 Mb copy number gain of chromosome region Xp22.33-p21.1 and a 52.2 Mb copy number gain of Yp11.2-qter, in addition to the intact X and Y chromosomes. Previously reported patients with XY sex reversal have not had DSS with corneal opacities, dysgenesis of the anterior segment of the eye, and unilateral multicystic dysplastic kidney. These findings represent a new form of XY sex reversal due to an Xp duplication.
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PMID:47, XY, +der(Y),t(X;Y)(p21.1;p11.2): a unique case of XY sex reversal. 2127 59

X-chromosome inactivation (XCI) is an essential mechanism in females that compensates for the genome imbalance between females and males. It is known that XCI can spread into an autosome of patients with X;autosome translocations. The subject was a 5-year-old boy with Prader-Willi syndrome (PWS)-like features including hypotonia, hypo-genitalism, hypo-pigmentation, and developmental delay. G-banding, fluorescent in situ hybridization, BrdU-incorporated replication, human androgen receptor gene locus assay, SNP microarrays, ChIP-on-chip assay, bisulfite sequencing, and real-time RT-PCR were performed. Cytogenetic analyses revealed that the karyotype was 46,XY,der(X)t(X;15)(p21.1;q11.2),-15. In the derivative chromosome, the X and half of the chromosome 15 segments showed late replication. The X segment was maternal, and the chromosome 15 region was paternal, indicating its post-zygotic origin. The two chromosome 15s had a biparental origin. The DNA methylation level was relatively high in the region proximal from the breakpoint, and the level decreased toward the middle of the chromosome 15 region; however, scattered areas of hypermethylation were found in the distal region. The promoter regions of the imprinted SNRPN and the non-imprinted OCA2 genes were completely and half methylated, respectively. However, no methylation was found in the adjacent imprinted gene UBE3A, which contained a lower density of LINE1 repeats. Our findings suggest that XCI spread into the paternal chromosome 15 led to the aberrant hypermethylation of SNRPN and OCA2 and their decreased expression, which contributes to the PWS-like features and hypo-pigmentation of the patient. To our knowledge, this is the first chromosome-wide methylation study in which the DNA methylation level is demonstrated in an autosome subject to XCI.
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PMID:Spread of X-chromosome inactivation into chromosome 15 is associated with Prader-Willi syndrome phenotype in a boy with a t(X;15)(p21.1;q11.2) translocation. 2173 74

Protein tyrosine phosphatase-like A (PTPLa) has been implicated in skeletal myogenesis and cardiogenesis. Mutations in PTPLa correlated with arrhythmogenic right ventricular dysplasia in humans and congenital centronuclear myopathy with severe hypotonia in dogs. The molecular mechanisms of PTPLa in myogenesis are unknown. In this report, we demonstrate that PTPLa is required for myoblast growth and differentiation. The cells lacking PTPLa remained immature and failed to differentiate into mature myotubes. The repressed MyoG expression was responsible for the impaired myoblast differentiation. Meanwhile, impeded cell growth, with an obvious S-phase arrest and compromised G(2)/M transition, was observed in PTPLa-deficient myoblasts. Further study demonstrated that the upregulation of cyclin D1 and cyclin E2 complexes, along with a compromised G(2)/M transition due to the decreased CDK1 (cyclin-dependent kinase 1) activity and upregulated p21, contributed to the mutant cell S-phase arrest and eventually led to the retarded cell growth. Finally, the transcriptional regulation of the PTPLa gene was explored. We identified PTPLa as a new target gene of the serum response factor (SRF). Skeletal- and cardiac-muscle-specific SRF knockouts resulted in significant decreases in PTPLa expression, suggesting a conserved transcriptional regulation of the PTPLa gene in mice.
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PMID:Protein tyrosine phosphatase-like A regulates myoblast proliferation and differentiation through MyoG and the cell cycling signaling pathway. 2875 70


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