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)

Microdeletion 12p13.33, though very rare, is an emerging condition associated with variable phenotype including a specific speech delay sound disorder, labelled childhood apraxia of speech (CAS), intellectual disability (ID) and neurobehavioral problems. Here we report a de novo 2.3 Mb interstitial 12p13.33-p13.32 deletion in a 5 year-old child with mild ID, speech delay, microcephaly, muscular hypotonia, and joint laxity. In contrast to previously reported patients with 12p13.33 monosomy, our patient's interstitial deletion spans the 12p13.33-12p13.32 region with the distal breakpoint within intron 12 of CACNA1C. Phenotype-genotype comparison between our case, previously reported patients, and subjects with 12p13.33 deletions led us to propose that haploinsufficiency of CACNA1C may influence the variability of the patients' phenotype, since the gene resulted disrupted or entirely deleted in the majority of reported patients. In addition, phenotypic features such as microcephaly, muscular hypotonia, and joint laxity are mainly present in patients with monosomy of 12p13.33 extending to the 12p13.32 portion. A common region of ~300 kb, harbouring EFCAB4B and PARP11, is deleted in patients with microcephaly while a second region of ~700 kb, including TSPAN9 and PMTR8, could be associated with muscle hypotonia and joint laxity. These data reinforce the hypothesis that multiple haploinsufficient genes and age-dependent observation may concur to generate the variable phenotype associated with 12p13.33 deletion.
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PMID:Genotype-phenotype relationship in a child with 2.3 Mb de novo interstitial 12p13.33-p13.32 deletion. 2478 Jun 30

Submicroscopic duplications of 5p13 have been recently reported in several cases, warranting the description of a new clinical entity (Chromosome 5p13 Duplication Syndrome; MIM 613174). These microduplications, while variable in size, all contain at least part of the NIPBL gene. Patients with duplications in this region present with intellectual disability/developmental delay (ID/DD) and dysmorphic facies. In addition, skeletal and brain abnormalities have been variably reported, as well as propensity for obesity in adulthood and hypotonia. We report a family with two affected sons and two affected daughters, each carrying a duplication at 5p13.2 encompassing the 3' portion of SLC1A3 and the 5' portion of NIPBL. Upon confirming the SNP microarray finding by FISH in the proband, it was discovered that the 5p13.2 duplication was located on the short arm of the X chromosome. Further FISH studies on the family demonstrated that all affected children and their mother carried a derivative X chromosome with insertion of material from 5p13.2 into the intermediate region of Xp [der(X)ins(X;5)(p2?2.1;p13.2p13.2)]. To our knowledge, this is the first report of an inherited duplication of 5p13.2 with multiple affected family members. This family underscores the need to confirm array findings by FISH, both in the proband and family members, to discern implications for pathogenicity and more accurately define the recurrence risk.
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PMID:Familial transmission of 5p13.2 duplication due to maternal der(X)ins(X;5). 2585 3

Prader-Willi syndrome (PWS) is a complex, multisystem genetic disorder characterized by endocrine, neurologic, and behavioral abnormalities. We report the first case of an unbalanced de novo reciprocal translocation of chromosomes 15 and 19, 45,XY,-15,der(19)t(15;19)(q12;p13.3), resulting in monosomy for the PWS critical chromosome region. Our patient had several typical features of PWS including infantile hypotonia, a poor suck and feeding difficulties, tantrums, skin picking, compulsions, small hands and feet, and food seeking, but not hypopigmentation, a micropenis, cryptorchidism or obesity as common findings seen in PWS at the time of examination at 6 years of age. He had seizures noted from 1 to 3 years of age and marked cognitive delay. High-resolution SNP microarray analysis identified an atypical PWS type I deletion in chromosome 15 involving the proximal breakpoint BP1. The deletion extended beyond the GABRB3 gene but was proximal to the usual distal breakpoint (BP3) within the 15q11q13 region, and GABRA5, GABRG3, and OCA2 genes were intact. No deletion of band 19p13.3 was detected; therefore, the patient was not at an increased risk of tumors from the Peutz-Jeghers syndrome associated with a deletion of the STK11 gene.
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PMID:Prader-Willi Syndrome due to an Unbalanced de novo Translocation t(15;19)(q12;p13.3). 2789 6

The GRIN2B (glutamate receptor, ionotropic, N-methyl-d-aspartate 2B) gene, located in the short arm of chromosome 12, encoding the NR2B subunit of the N-methyl-D-aspartate receptor, has recently been recognized to play an important role in corticogenesis and brain plasticity. Deletions in the short arm of chromosome 12 are rare. Hemizygous loss of function of the GRIN2B gene results in developmental delay, whereas gain of function leads to epilepsy, and infantile spasms in particular. In addition, GRIN2B variants have been associated with autism spectrum disorder and schizophrenia. Here the authors report a child with global developmental delay, autistic behavioural features, central hypotonia, dysmorphic features and isolated congenital anomalies of the fingers and toes, and a de novo heterozygous deletion in chromosome locus 12p13.2-p13.1, involving loss of several genes, including GRIN2B. This report and our review of the literature help clarify the distinct phenotypes associated with loss or gain of GRIN2B function.
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PMID:Chromosome 12p Deletion Spanning the GRIN2B Gene Presenting With a Neurodevelopmental Phenotype: A Case Report and Review of Literature. 2850 5

Copy number variation in loss of 3p13 is an infrequently reported entity characterized by hypertelorism, aniridia, microphthalmia, high palate, neurosensorial deafness, camptodactyly, heart malformation, development delay, autism spectrum disorder, seizures, and choanal atresia. The entity is caused probably by haploinsufficiency for FOXP1, UBA3, FAM19A1, and MITF. We report a newborn male with hypotonia, facial dysmorphism, heart malformation, and without clinical diagnosis; nevertheless, the use of appropriate genetic test, such us the chromosomal microarray analysis allowed identification of a copy number variant in loss of 5.5 Mb at chromosome 3 (p13-p14.1), that included 54 genes, encompassing FOXP1 gene. We compare the findings in our Peruvian patient to those of earlier reported patients; furthermore, add new signs for this entity.
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PMID:Peruvian Newborn Male with 3p13 Deletion Syndrome Encompassing the FOXP1 Gene: Review of the Literature. 3276 32


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