Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Disorders known to be caused by molecular and cytogenetic abnormalities of the proximal short arm of chromosome 17 include Charcot-Marie-Tooth disease type 1A (CMT1A), hereditary neuropathy with liability to pressure palsies (HNPP), Smith-Magenis syndrome (SMS), and mental retardation and congenital anomalies associated with partial duplication of 17p. We identified a patient with multifocal mononeuropathies and mild distal neuropathy, growth hormone deficiency, and mild mental retardation who was found to have a duplication of the SMS region of 17p11.2 and a deletion of the peripheral myelin protein 22 (PMP22) gene within 17p12 on the homologous chromosome. Further molecular analyses reveal that the dup(17)(p11.2p11.2) is a de novo event but that the PMP22 deletion is familial. The family members with deletions of PMP22 have abnormalities indicative of carpal tunnel syndrome, documented by electrophysiological studies prior to molecular analysis. The chromosomal duplication was shown by interphase FISH analysis to be a tandem duplication. These data indicate that familial entrapment neuropathies, such as carpal tunnel syndrome and focal ulnar neuropathy syndrome, can occur because of deletions of the PMP22 gene. The co-occurrence of the 17p11.2 duplication and the PMP22 deletion in this patient likely reflects the relatively high frequency at which these abnormalities arise and the underlying molecular characteristics of the genome in this region.
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PMID:DNA rearrangements on both homologues of chromosome 17 in a mildly delayed individual with a family history of autosomal dominant carpal tunnel syndrome. 997 84

We report a case of dystonia with a partial deletion of the short arm (p) of chromosome 18 and androgen insensitivity. Neurologic findings in the 18p syndrome are reported to include mental retardation, seizures, incoordination, tremor, and chorea. A 15-year-old girl with a denovo 18p deletion [karyotype 46, XY, del (18)(p11.1)] developed progressive asymmetric dystonia. She had oromotor apraxia and partial expressive aphasia since childhood, and she was able to partially communicate through elementary sign language. At the age of 15 years, she developed subacute and progressive choreic movements of the right arm, severe dystonic posturing of the left arm, and spastic dystonia in both legs. Her response to parenteral or oral benzodiazepines, oral trihexyphenidyl, benztropine mesylate, baclofen, and L-dopa were brief and inadequate. The response to intrathecal baclofen has been sustained over 18 months. In all likelihood, the 18p deletion syndrome affecting this patient is significant in the pathogenesis of her acquired dystonia. Chronic intrathecal baclofen therapy via pump has been effective in this case and should be considered as a treatment modality in carefully selected patients with dystonia.
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PMID:Progressive dystonia in a child with chromosome 18p deletion, treated with intrathecal baclofen. 1007 26

Two families with nonspecific X-linked mental retardation (MRX) are presented. In the first family, MRX51, three male patients showed mild to borderline mental retardation. Multipoint linkage analysis yielded a maximal LOD score of 2.10 between markers DXS8012 and DXS1003, localizing the MRX51 gene at Xp11.3-p11.23. In the second family, XLMR7, three men showed moderate mental retardation (MR), and one possible female carrier had mild MR. Multipoint linkage analysis yielded an LOD score of 1.80 between markers DXS8063 and DXS1047, situating the disease gene at Xq23-q26.1. When the analysis was performed considering the affected female to be an expressing heterozygote carrier of the disease mutation, a maximal LOD score of 2.10 was found in the same region.
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PMID:Regional localization of a gene for nonspecific XLMR to Xp11.3-p11. 23 (MRX51) and tentative localization of an MRX gene to Xq23-q26.1. 1039 44

Four families are described in which mental retardation segregates in an X-linked fashion. Mental retardation was the only consistent clinical finding in all affected males. The degree of retardation varied from mild to profound both between and within families. Linkage analysis localized the genetic defect of MRX43 to Xp22. 31-p21.2, MRX44 to Xp11.3-p11.21, MRX45 to Xp11.3-p11.21, and MRX52 to Xp11.21-q21.33 with LOD scores of >2 at straight theta = 0.0 in all four families.
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PMID:Four families (MRX43, MRX44, MRX45, MRX52) with nonspecific X-linked mental retardation: clinical and psychometric data and results of linkage analysis. 1039 46

Tandem repeats of a novel, putative, zinc-binding motif (MYM) have been described within the products of two, highly homologous genes: ZNF198/RAMP/FIM and ZNF261/DXS6673E. ZNF198, mapping to 13q11-q12, was recently shown to fuse to the fibroblast growth factor receptor 1 gene in the t(8;13)(p11;q11-q12) rearrangement associated with a stem cell leukemia/lymphoma syndrome. ZNF261 at Xq13.1 is disrupted by a t(X;13)(q13.1;q32) rearrangement in a mentally retarded patient and is a candidate gene for nonspecific X-linked mental retardation. Here we have cloned another member of this family, designated ZNF258, and mapped it to chromosome band 14q12. In addition, ZNF262/KIAA0425 was identified as a further member of the family and mapped to 1p32-p34. The predicted protein products of ZNF258 and ZNF262 maintain the repeats of the MYM motif. Isolation of these new members will facilitate the functional characterization of the MYM family and motif.
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PMID:Cloning and mapping of members of the MYM family. 1048 18

Two unrelated mildly retarded males with inversions of the X chromosome and non-specific mental retardation (MRX) are described. Case 1 has a pericentric inversion 46,Y,inv(X) (p11.1q13.1) and case 2 a paracentric inversion 46,Y,inv(X) (q13.1q28). Both male patients have severe learning difficulties. The same chromosomal abnormalities were found in their mothers who are intellectually normal. Fluorescence in situ hybridisation mapping showed a common area of breakage of each of the inverted chromosomes in Xq13.1 near DXS131 and DXS162. A detailed long range restriction map of the breakpoint region was constructed using YAC, PAC, and cosmid clones. We show that the two inverted chromosomes break within a short 250 kb region. Moreover, a group of ESTs corresponding to an as yet uncharacterised gene was mapped to the same critical interval. We hypothesise that the common inversion breakpoint region of the two cases in Xq13.1 may contain a new MRX gene.
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PMID:Two unrelated patients with inversions of the X chromosome and non-specific mental retardation: physical and transcriptional mapping of their common breakpoint region in Xq13.1. 1052 54

A small ring-shaped supernumerary marker chromosome (SMC) was detected in 50% of metaphase cells in an 18-month-old boy with mental retardation and multiple congenital anomalies. Conventional cytogenetic methods had failed to identify the origin of the marker. When the patient was age 11.5 years, we defined the origin of the SMC by fluorescence in situ hybridization using a battery of centromere-specific DNA probes. The marker was positive with the probe for locus D2Z. More detailed characterization was achieved by using chromosome 2 arm-specific and marker-specific DNA libraries, which were constructed by microdissection of the two arms chromosome 2 and SMC with subsequent amplification of the chromosomal material by a degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR). The marker was identified as r(2)(p11.2-->q14.1). The propositus had dolichocephaly, coarse hair, low-set ears, exophthalmos, epicanthal folds, strabismus, depressed nasal bridge, high-arched palate, excess of skin on the neck, tapered fingers with mild clinodactyly, talipes varus on the right, inguinal hernia, hypogenitalism, muscular hypotonia, and mental retardation. This is the first case of SMC derived from chromosome 2 that was characterized by forward and reverse chromosome painting.
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PMID:Characterization of a small supernumerary ring marker derived from chromosome 2 by forward and reverse chromosome painting. 1056 73

Recombination between repeated sequences at various loci of the human genome are known to give rise to DNA rearrangements associated with many genetic disorders. Perhaps the most extensively characterized genomic region prone to rearrangement is 17p12, which is associated with the peripheral neuropathies, hereditary neuropathy with liability to pressure palsies (HNPP) and Charcot-Marie-Tooth disease type 1A (CMT1A;ref. 2). Homologous recombination between 24-kb flanking repeats, termed CMT1A-REPs, results in a 1.5-Mb deletion that is associated with HNPP, and the reciprocal duplication product is associated with CMT1A (ref. 2). Smith-Magenis syndrome (SMS) is a multiple congenital anomalies, mental retardation syndrome associated with a chromosome 17 microdeletion, del(17)(p11.2p11.2) (ref. 3,4). Most patients (>90%) carry deletions of the same genetic markers and define a common deletion. We report seven unrelated patients with de novo duplications of the same region deleted in SMS. A unique junction fragment, of the same apparent size, was identified in each patient by pulsed field gel electrophoresis (PFGE). Further molecular analyses suggest that the de novo17p11.2 duplication is preferentially paternal in origin, arises from unequal crossing over due to homologous recombination between flanking repeat gene clusters and probably represents the reciprocal recombination product of the SMS deletion. The clinical phenotype resulting from duplication [dup(17)(p11.2p11.2)] is milder than that associated with deficiency of this genomic region. This mechanism of reciprocal deletion and duplication via homologous recombination may not only pertain to the 17p11.2 region, but may also be common to other regions of the genome where interstitial microdeletion syndromes have been defined.
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PMID:Molecular mechanism for duplication 17p11.2- the homologous recombination reciprocal of the Smith-Magenis microdeletion. 1061 34

Wolf-Hirschhorn Syndrome (WHS) is caused by distal deletion of the short arm of chromosome 4 and is characterized by growth deficiency, mental retardation, a distinctive, 'greek-helmet' facial appearance, microcephaly, ear lobe anomalies, and sacral dimples. We report a family with a balanced chromosomal translocation 4;18(p15.32;p11.21) in the father and an unbalanced translocation resulting in partial monosomy 4 and partial trisomy 18 in one living boy and a prenatally diagnosed male fetus. Both showed abnormalities consistent with WHS and had in addition aplasia of one umbilical artery. Karyotyping of another stillborn fetus revealed a supernumerary derivative chromosome der(18)t(4;18)(p15.32;p11.21) of paternal origin and two normal chromosomes 4. The umbilical cord had three normal vessels. A third stillborn fetus with the same balanced translocation as the father had a single umbilical artery and hygroma colli.
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PMID:Prenatal diagnosis of a fetus with a cryptic translocation 4p;18p and Wolf-Hirschhorn syndrome (WHS). 1069 89

Ring chromosome 22 has been described in over 50 cases. A characteristic phenotype has not been fully delineated; however, long face, thick eyebrows, 2-3 toe syndactyly, mental retardation, adequate somatic growth and the absence of major malformations are noted in many cases. An 11-year-old boy with ring chromosome 22 and 46,XY,r(22)(p11.31-q13.31 approximately q13.33) karyotype presented with global developmental delay, autistic disorder, and dolichocephaly, apparently low-set and large ears, midface hypoplasia, and 2-3 toe syndactyly. This is the second report of a ring chromosome 22 with autistic disorder. There appears to be an association between abnormalities of chromosome 22, including r(22), and autistic disorder; however, this occurrence may be a result of the association of autistic disorder with mental retardation rather than specifically due to r(22). The physical findings in this case also suggest that ring chromosome 22 causes a subtle but distinct phenotype which has previously been proposed.
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PMID:Ring chromosome 22 and autism: report and review. 1070 59


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