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1.
Charcot-Marie-Tooth type X1 disease (CMTX1) is an X-dominant peripheral neuropathy caused by mutations in the GJB1 gene. Molecular genetic analysis of the GJB1 gene is crucial for CMTX1 diagnosis and for genetic counselling. To date, molecular genetic analysis of the GJB1 gene revealed 264 mutations in the GJB1 gene. In spite of the rising number of GJB1 gene mutations, family history was documented in only a few CMTX1 cases. The aim of this study was a molecular genetic analysis of the GJB1 gene in 7 families, performed in 19 CMTX1-affected patients and 13 healthy family members. Moreover, we attempted to report evidence of effects of 6 amino-acid substitutions described in this study. To the best of our knowledge, the G110D, V152D and K167E mutations are novel substitutions, which have not been reported so far. 相似文献
2.
de Brouwer AP Williams KL Duley JA van Kuilenburg AB Nabuurs SB Egmont-Petersen M Lugtenberg D Zoetekouw L Banning MJ Roeffen M Hamel BC Weaving L Ouvrier RA Donald JA Wevers RA Christodoulou J van Bokhoven H 《American journal of human genetics》2007,81(3):507-518
Arts syndrome is an X-linked disorder characterized by mental retardation, early-onset hypotonia, ataxia, delayed motor development, hearing impairment, and optic atrophy. Linkage analysis in a Dutch family and an Australian family suggested that the candidate gene maps to Xq22.1-q24. Oligonucleotide microarray expression profiling of fibroblasts from two probands of the Dutch family revealed reduced expression levels of the phosphoribosyl pyrophosphate synthetase 1 gene (PRPS1). Subsequent sequencing of PRPS1 led to the identification of two different missense mutations, c.455T-->C (p.L152P) in the Dutch family and c.398A-->C (p.Q133P) in the Australian family. Both mutations result in a loss of phosphoribosyl pyrophosphate synthetase 1 activity, as was shown in silico by molecular modeling and was shown in vitro by phosphoribosyl pyrophosphate synthetase activity assays in erythrocytes and fibroblasts from patients. This is in contrast to the gain-of-function mutations in PRPS1 that were identified previously in PRPS-related gout. The loss-of-function mutations of PRPS1 likely result in impaired purine biosynthesis, which is supported by the undetectable hypoxanthine in urine and the reduced uric acid levels in serum from patients. To replenish low levels of purines, treatment with S-adenosylmethionine theoretically could have therapeutic efficacy, and a clinical trial involving the two affected Australian brothers is currently underway. 相似文献
3.
Linkage localization of X-linked Charcot-Marie-Tooth disease. 总被引:7,自引:3,他引:4
J Bergoffen J Trofatter M A Pericak-Vance J L Haines P F Chance K H Fischbeck 《American journal of human genetics》1993,52(2):312-318
Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory neuropathy, is a heterogeneous group of slowly progressive, degenerative disorders of peripheral nerve. X-linked CMT (CMTX) (McKusick 302800), a subdivision of type I, or demyelinating, CMT is an X-linked dominant condition with variable penetrance. Previous linkage analysis using RFLPs demonstrated linkage to markers on the proximal long and short arms of the X chromosome, with the more likely localization on the proximal long arm of the X chromosome. Available variable simple-sequence repeats (VSSRs) broaden the possibilities for linkage analysis. This paper presents new linkage data and recombination analysis derived from work with four VSSR markers--AR, PGKP1, DXS453, and DXYS1X--in addition to analysis using RFLP markers described elsewhere. These studies localize the CMTX gene to the proximal Xq segment between PGKP1 (Xq11.2-12) and DXS72 (Xq21.1), with a combined maximum multipoint lod score of 15.3 at DXS453 (theta = 0). 相似文献
4.
Xuezhong Liu Dongyi Han Jianzhong Li Xiaomei Ouyang Xu Li Zhanguo Jin Maria Bitner-Glindzicz Heng Xu Roland D. Eavey Jonathan G. Seidman Li L. Du Pu Dai Denise Yan 《American journal of human genetics》2010,86(1):65-627
We report a large Chinese family with X-linked postlingual nonsyndromic hearing impairment in which the critical linkage interval spans a genetic distance of 5.41 cM and a physical distance of 15.1 Mb that overlaps the DFN2 locus. Mutation screening of the PRPS1 gene in this family and in the three previously reported DFN2 families identified four different missense mutations in PRPS1. These mutations result in a loss of phosphoribosyl pyrophosphate (PRPP) synthetase 1 activity, as was shown in silico by structural analysis and was shown in vitro by enzymatic activity assays in erythrocytes and fibroblasts from patients. By in situ hybridization, we demonstrate expression of Prps1 in murine vestibular and cochlea hair cells, with continuous expression in hair cells and postnatal expression in the spiral ganglion. Being the second identified gene associated with X-linked nonsyndromic deafness, PRPS1 will be a good candidate gene for genetic testing for X-linked nonsyndromic hearing loss. 相似文献
5.
Sylvia Bort E. Nelis Vincent Timmerman Teresa Sevilla Antonio Cruz-Martínez Francisco Martínez José M. Millán Javier Arpa Juan J. Vílchez Felix Prieto Christine Van Broeckhoven F. Palau 《Human genetics》1997,99(6):746-754
Charcot-Marie-Tooth disease (CMT) and hereditary neuropathy with liability to pressure palsies (HNPP) are two inherited peripheral
neuropathies. The most prevalent mutations are a reciprocal 1.5-Mb duplication and 1.5-Mb deletion, respectively, at the CMT1A/HNPP
locus on chromosome 17p11.2. Point mutations in the coding region of the myelin genes, peripheral myelin protein 22 (PMP22),
myelin protein zero (MPZ) or connexin 32 (Cx32) have been reported in CMT patients, including CMT type 1 (CMT1), CMT type
2 (CMT2) and Déjérine-Sottas neuropathy (DS) patients, and only in the coding region of PMP22 in HNPP families lacking a deletion.
We have investigated point and small mutations in the MPZ, PMP22 and Cx32 genes in a series of patients of Spanish ancestry:
47 CMT patients without duplications, and 5 HNPP patients without deletions. We found 15 different mutations in 16 CMT patients
(34%). Nine different mutations in ten patients were detected in the Cx32 gene, this being the most frequently involved gene
in this series, whereas five mutations involved the MPZ gene and only one the PMP22 gene. Six out of nine nucleotide substitutions
in the Cx32 gene involved two codons encoding arginine at positions 164 and 183, suggesting that these two codons may constitute
two Cx32 regions prone to mutate in the Spanish population. Analysis of HNPP patients revealed a 5′ splicing mutation in intron
1 of the PMP22 gene in a family with autosomal dominance, which confirms allelic heterogeneity in HNPP. Ectopic mRNA analysis
on leukocytes suggests that this mutation might behave as a null allele.
Received: 25 July 1996 / Revised: 15 November 1996 相似文献
6.
X-linked dominant Charcot-Marie-Tooth neuropathy (CMTX): new mutations in the connexin32 gene 总被引:2,自引:0,他引:2
Catherine Ressot Philippe Latour Françoise Blanquet-Grossard Franck Sturtz Sylvie Duthel Jacques Battin Emmanuel Corbillon Elizabeth Ollagnon Françoise Serville Antoon Vandenberghe André Dautigny D. Pham-Dinh 《Human genetics》1996,98(2):172-175
X-linked dominant Charcot-Marie-Tooth (CMTX) neuropathy has been mapped to the Xq13 region. Subsequently, several mutations
that could account for CMTX have been detected in the coding part of the connexin32 (Cx32) gene, which is located within this
region. In order to develop more specific diagnostic tools, we have begun a systematic screening of families with dominant
CMTX for mutations in the coding region of the Cx32 gene. This report describes a study of ten families and different mutations
segregating with the disease were detected in five of them. In addition to the previously reported Arg22stop and Arg215Trp
substitutions, three novel mutations are described, including two different missense mutations at codon Arg22 (Arg22Pro and
Arg22Gly), and a nonsense mutation at codon Trp133. The identification of new CMTX-causing mutations is a critical step for
carrier detection and presymptomatic diagnosis, and should provide essential information on the structure-function relationship
of Cx32 in vitro as well as in vivo.
Received: 11 January 1996 / Revised: 29 March 1996 相似文献
7.
Seung-Hyun Bae Jeong-In Baek Jong Dae Lee Mee Hyun Song Tae-Jun Kwon Se-Kyung Oh Ji Yun Jeong Jae Young Choi Kyu-Yup Lee Un-Kyung Kim 《Gene》2013
Auditory neuropathy spectrum disorder (ANSD) is caused by dys-synchronous auditory neural response as a result of impairment of the functions of the auditory nerve or inner hair cells, or synapses between inner hair cells and the auditory nerve. To identify a causative gene causing ANSD in the Korean population, we conducted gene screening of the OTOF, DIAPH3, and PJVK genes in 19 unrelated Korean patients with ANSD. A novel nonsense mutation (p.Y1064X) and a known pathogenic mutation (p.R1939Q) of the OTOF gene were identified in a patient as compound heterozygote. Pedigree analysis for these mutations showed co-segregation of mutation genotype and the disease in the family, and it supported that the p.Y1064X might be a novel genetic cause of autosomal recessive ANSD. A novel missense variant p.K1017R (c.3050A>G) in the DIAPH3 gene was also identified in the heterozygous state. In contrast, no mutation was detected in the PJVK gene. These results indicate that no major causative gene has been reported to date in the Korean population and that pathogenic mutations in undiscovered candidate genes may have an effect on ANSD. 相似文献
8.
Rivière JB Ramalingam S Lavastre V Shekarabi M Holbert S Lafontaine J Srour M Merner N Rochefort D Hince P Gaudet R Mes-Masson AM Baets J Houlden H Brais B Nicholson GA Van Esch H Nafissi S De Jonghe P Reilly MM Timmerman V Dion PA Rouleau GA 《American journal of human genetics》2011,89(2):767-230
Hereditary sensory and autonomic neuropathy type II (HSANII) is a rare autosomal-recessive disorder characterized by peripheral nerve degeneration resulting in a severe distal sensory loss. Although mutations in FAM134B and the HSN2 exon of WNK1 were associated with HSANII, the etiology of a substantial number of cases remains unexplained. In addition, the functions of WNK1/HSN2 and FAM134B and their role in the peripheral nervous system remain poorly understood. Using a yeast two-hybrid screen, we found that KIF1A, an axonal transporter of synaptic vesicles, interacts with the domain encoded by the HSN2 exon. In parallel to this screen, we performed genome-wide homozygosity mapping in a consanguineous Afghan family affected by HSANII and identified a unique region of homozygosity located on chromosome 2q37.3 and spanning the KIF1A gene locus. Sequencing of KIF1A in this family revealed a truncating mutation segregating with the disease phenotype. Subsequent sequencing of KIF1A in a series of 112 unrelated patients with features belonging to the clinical spectrum of ulcero-mutilating sensory neuropathies revealed truncating mutations in three additional families, thus indicating that mutations in KIF1A are a rare cause of HSANII. Similarly to WNK1 mutations, pathogenic mutations in KIF1A were almost exclusively restricted to an alternatively spliced exon. This study provides additional insights into the molecular pathogenesis of HSANII and highlights the potential biological relevance of alternative splicing in the peripheral sensory nervous system. 相似文献
9.
Boerkoel CF Takashima H Stankiewicz P Garcia CA Leber SM Rhee-Morris L Lupski JR 《American journal of human genetics》2001,68(2):325-333
The periaxin gene (PRX) encodes two PDZ-domain proteins, L- and S-periaxin, that are required for maintenance of peripheral nerve myelin. Prx(-/-) mice develop a severe demyelinating peripheral neuropathy, despite apparently normal initial formation of myelin sheaths. We hypothesized that mutations in PRX could cause human peripheral myelinopathies. In accordance with this, we identified three unrelated Dejerine-Sottas neuropathy patients with recessive PRX mutations-two with compound heterozygous nonsense and frameshift mutations, and one with a homozygous frameshift mutation. We mapped PRX to 19q13.13-13.2, a region recently associated with a severe autosomal recessive demyelinating neuropathy in a Lebanese family (Delague et al. 2000) and syntenic to the location of Prx on murine chromosome 7 (Gillespie et al. 1997). 相似文献
10.
11.
Evidence for genetic heterogeneity underlying hereditary neuropathy with liability to pressure palsies 总被引:3,自引:0,他引:3
E. C. M. Mariman A. A. W. M. Gabreëls-Festen S. E. C. van Beersum P. J. H. Jongen E. van de Looij F. Baas P. A. Bolhuis H. H. Ropers F. J. M. Gabreëls 《Human genetics》1994,93(2):151-156
Hereditary neuropathy with liability to pressure palsies (HNPP) is a disorder of the peripheral nervous system, the cause of which has recently been identified as a deletion on chromosome 17p. The deletion corresponds to the duplication that is commonly observed in patients with hereditary motor and sensory neuropathy type Ia (HMSNIa, 17p11.2–p12). Therefore, the gene for peripheral myelin protein 22 (PMP-22) is a candidate gene for both HMSNIa and HNPP. Here, we show that a similar deletion is present in one family with HNPP but is clearly absent in another family. Affected members of this family carry the expected two copies of the PMP-22 gene and the surrounding region. Furthermore, linkage analyses of this family exclude a large part of 17p, spanning the area deleted in other families with HNPP, as the location for the disease gene. These data strongly argue for the existence of genetic heterogeneity underlying HNPP. Results from two-point linkage analysis with markers on chromosome 1q are inconsistent with a possible involvement of the locus for HMSNIb in the present family. 相似文献
12.
Resko P Radvansky J Odnogova Z Baldovic M Minarik G Polakova H Palffy R Kadasi L 《General physiology and biophysics》2011,30(4):379-388
Charcot-Marie-Tooth disease (CMT) and related peripheral neuropathies are the most commonly inherited neurological disorders in humans, characterized by clinical and genetic heterogeneity. The most prevalent clinical entities belonging to this group of disorders are CMT type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP). CMT1A and HNPP are predominantly caused by a 1.5 Mb duplication and deletion in the chromosomal region 17p11.2, respectively, and less frequently by other mutations in the peripheral myelin protein 22 (PMP22) gene. Despite being relatively common diseases, they haven't been previously studied in the Slovak population. Therefore, the aim of this study was to identify the spectrum and frequency of PMP22 mutations in the Slovak population by screening 119 families with CMT and 2 families with HNPP for causative mutations in this gene. The copy number determination of PMP22 resulted in the detection of CMT1A duplication in 40 families and the detection of HNPP deletion in 7 families, 6 of which were originally diagnosed as CMT. Consequent mutation screening of families without duplication or deletion using dHPLC and sequencing identified 6 single base changes (3 unpublished to date), from which only c.327C>A (Cys109X) present in one family was provably causative. These results confirm the leading role of PMP22 mutation analysis in the differential diagnosis of CMT and show that the spectrum and frequency of PMP22 mutations in the Slovak population is comparable to that seen in the global population. 相似文献
13.
Eun Kyung Park Ki Wha Chung Kyu Sun Lee Hye Jin Lee Bo Ram Yun Je-Nyun Kim Jong Hyu Shin Byung-Ok Choi 《Genes & genomics.》2011,33(6):659-664
Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous peripheral neuropathy. Myelin protein zero (MPZ) is a major myelin protein of the peripheral nerve and mutations in its gene cause a wide phenotypic spectrum including CMT1B, CMT2I, CMT2J and Dejerine-Sottas syndrome. The objective of this study was to find the causative mutation in a Korean large autosomal dominant demyelinating CMT family (FC240). Clinical disabilities were measured by a functional disability scale (FDS), a CMT neuropathy score (CMTNS), and a 9-hole peg test (9-HPT). Mutational analysis of the FC240 family revealed a novel c.410G>A (Gly137Asp) mutation in the MPZ gene. The mutation was completely co-segregated with affected members in the family, and was not found in controls. The clinical features and electrophysiological findings were compatible with CMT1B. Clinical symptoms revealed phenotypic diversities among family members and generations within the same family. In addition, the present patients with Gly137Asp mutation showed earlier age at onset and slow progression than the reported patient with Gly137Ser. Therefore, it seems that there were wide phenotypic variations within the same family harboring Gly137Asp mutation, and between Gly137Asp and Gly137Ser mutations. 相似文献
14.
Guelly C Zhu PP Leonardis L Papić L Zidar J Schabhüttl M Strohmaier H Weis J Strom TM Baets J Willems J De Jonghe P Reilly MM Fröhlich E Hatz M Trajanoski S Pieber TR Janecke AR Blackstone C Auer-Grumbach M 《American journal of human genetics》2011,(1):948-105
Hereditary sensory neuropathy type I (HSN I) is an axonal form of autosomal-dominant hereditary motor and sensory neuropathy distinguished by prominent sensory loss that leads to painless injuries. Unrecognized, these can result in delayed wound healing and osteomyelitis, necessitating distal amputations. To elucidate the genetic basis of an HSN I subtype in a family in which mutations in the few known HSN I genes had been excluded, we employed massive parallel exon sequencing of the 14.3 Mb disease interval on chromosome 14q. We detected a missense mutation (c.1065C>A, p.Asn355Lys) in atlastin-1 (ATL1), a gene that is known to be mutated in early-onset hereditary spastic paraplegia SPG3A and that encodes the large dynamin-related GTPase atlastin-1. The mutant protein exhibited reduced GTPase activity and prominently disrupted ER network morphology when expressed in COS7 cells, strongly supporting pathogenicity. An expanded screen in 115 additional HSN I patients identified two further dominant ATL1 mutations (c.196G>C [p.Glu66Gln] and c.976 delG [p.Val326TrpfsX8]). This study highlights an unexpected major role for atlastin-1 in the function of sensory neurons and identifies HSN I and SPG3A as allelic disorders. 相似文献
15.
G Nishimura E Lausch R Savarirayan M Shiba J Spranger B Zabel S Ikegawa A Superti-Furga S Unger 《American journal of medical genetics. Part C, Seminars in medical genetics》2012,(3):190-204
Dominant mutations in the TRPV4 gene result in a bone dysplasia family and form a continuous phenotypic spectrum that includes, in decreasing severity, lethal, and nonlethal metatropic dysplasia (MD), spondylometaphyseal dysplasia Kozlowski type (SMDK), and autosomal dominant brachyolmia. Several rare variant phenotypes that have some overlap but deviate in some ways from the general pattern have also been described. The known variant phenotypes are spondyloepiphyseal dysplasia Maroteaux type (Pseudo-Morquio type 2), parastremmatic dysplasia, and familial digital arthropathy with brachydactyly. Interestingly, different TRPV4 mutations have been associated with dominantly inherited neurologic disorders such as congenital spinal muscular atrophy and hereditary motor and sensory neuropathy. Finally, a small number of patients have been identified in whom a TRPV4 mutation results in a phenotype combining skeletal dysplasia with peripheral neuropathy. The TRPV4 gene encodes a regulated calcium channel implicated in multiple and diverse cellular processes. Over 50 different TRPV4 mutations have been reported, with two codons appearing to be mutational hot spots: P799 in exon 15, mostly associated with MD, and R594 in exon 11, associated with SMDK. While most pathogenic mutations tested so far result in activation of the calcium channel in vitro, the mechanisms through which TRPV4 activation results in skeletal dysplasia and/or peripheral neuropathy remain unclear and the genotype-phenotype correlations in this group of disorders remains somewhat mysterious. Since the phenotypic expression of most mutations seems to be relatively constant, careful clinical and radiographic assessment is useful in directing molecular analysis. 相似文献
16.
An active dominant mutation of glycyl-tRNA synthetase causes neuropathy in a Charcot-Marie-Tooth 2D mouse model 总被引:7,自引:0,他引:7
Of the many inherited Charcot-Marie-Tooth peripheral neuropathies, type 2D (CMT2D) is caused by dominant point mutations in the gene GARS, encoding glycyl tRNA synthetase (GlyRS). Here we report a dominant mutation in Gars that causes neuropathy in the mouse. Importantly, both sensory and motor axons are affected, and the dominant phenotype is not caused by a loss of the GlyRS aminoacylation function. Mutant mice have abnormal neuromuscular junction morphology and impaired transmission, reduced nerve conduction velocities, and a loss of large-diameter peripheral axons, without defects in myelination. The mutant GlyRS enzyme retains aminoacylation activity, and a loss-of-function allele, generated by a gene-trap insertion, shows no dominant phenotype in mice. These results indicate that the CMT2D phenotype is caused not by reduction of the canonical GlyRS activity and insufficiencies in protein synthesis, but instead by novel pathogenic roles for the mutant GlyRS that specifically affect peripheral neurons. 相似文献
17.
Rotthier A Auer-Grumbach M Janssens K Baets J Penno A Almeida-Souza L Van Hoof K Jacobs A De Vriendt E Schlotter-Weigel B Löscher W Vondráček P Seeman P De Jonghe P Van Dijck P Jordanova A Hornemann T Timmerman V 《American journal of human genetics》2010,87(4):513-4745
Hereditary sensory and autonomic neuropathy type I (HSAN-I) is an axonal peripheral neuropathy associated with progressive distal sensory loss and severe ulcerations. Mutations in the first subunit of the enzyme serine palmitoyltransferase (SPT) have been associated with HSAN-I. The SPT enzyme catalyzes the first and rate-limiting step in the de novo sphingolipid synthesis pathway. However, different studies suggest the implication of other genes in the pathology of HSAN-I. Therefore, we screened the two other known subunits of SPT, SPTLC2 and SPTLC3, in a cohort of 78 HSAN patients. No mutations were found in SPTLC3, but we identified three heterozygous missense mutations in the SPTLC2 subunit of SPT in four families presenting with a typical HSAN-I phenotype. We demonstrate that these mutations result in a partial to complete loss of SPT activity in vitro and in vivo. Moreover, they cause the accumulation of the atypical and neurotoxic sphingoid metabolite 1-deoxy-sphinganine. Our findings extend the genetic heterogeneity in HSAN-I and enlarge the group of HSAN neuropathies associated with SPT defects. We further show that HSAN-I is consistently associated with an increased formation of the neurotoxic 1-deoxysphinganine, suggesting a common pathomechanism for HSAN-I. 相似文献
18.
Oral curcumin mitigates the clinical and neuropathologic phenotype of the Trembler-J mouse: a potential therapy for inherited neuropathy
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Khajavi M Shiga K Wiszniewski W He F Shaw CA Yan J Wensel TG Snipes GJ Lupski JR 《American journal of human genetics》2007,81(3):438-453
Mutations in myelin genes cause inherited peripheral neuropathies that range in severity from adult-onset Charcot-Marie-Tooth disease type 1 to childhood-onset Dejerine-Sottas neuropathy and congenital hypomyelinating neuropathy. Many myelin gene mutants that cause severe disease, such as those in the myelin protein zero gene (MPZ) and the peripheral myelin protein 22 gene (PMP22), appear to make aberrant proteins that accumulate primarily within the endoplasmic reticulum (ER), resulting in Schwann cell death by apoptosis and, subsequently, peripheral neuropathy. We previously showed that curcumin supplementation could abrogate ER retention and aggregation-induced apoptosis associated with neuropathy-causing MPZ mutants. We now show reduced apoptosis after curcumin treatment of cells in tissue culture that express PMP22 mutants. Furthermore, we demonstrate that oral administration of curcumin partially mitigates the severe neuropathy phenotype of the Trembler-J mouse model in a dose-dependent manner. Administration of curcumin significantly decreases the percentage of apoptotic Schwann cells and results in increased number and size of myelinated axons in sciatic nerves, leading to improved motor performance. Our findings indicate that curcumin treatment is sufficient to relieve the toxic effect of mutant aggregation-induced apoptosis and improves the neuropathologic phenotype in an animal model of human neuropathy, suggesting a potential therapeutic role in selected forms of inherited peripheral neuropathies. 相似文献
19.
Leal A 《Revista de biología tropical》2004,52(3):475-483
Hereditary motor and sensory neuropathy (HMSN) or Charcot-Marie-Tooth disease (CMT) is the most common hereditary illness of the peripheral nervous system. The genetics and the physiopathological aspects of the disease clarified until know, are here summarized. More than twenty genes and ten additional loci have been related with HMSN. These findings contribute to understand the metabolism of peripheral nerves and give the basis for molecular diagnostics and future therapy. Several Costa Rican families with CMT have been identified, specially with axonal forms. Two families present mutations in the myelin protein zero gene (IMPZ). In addition, linkage have been found between the disease and locus 19q13.3 in an extended family, and a mutation segregating with the disease is present in a candidate gene of the critical interval. Costa Rica has several advantages for genetical studies, that can contribute importantly in the generation of knowledge in the neurogenetical field. 相似文献
20.
Cloning of cDNAs for human phosphoribosylpyrophosphate synthetases 1 and 2 and X chromosome localization of PRPS1 and PRPS2 genes 总被引:3,自引:0,他引:3
M A Becker S A Heidler G I Bell S Seino M M Le Beau C A Westbrook W Neuman L J Shapiro T K Mohandas B J Roessler 《Genomics》1990,8(3):555-561
Cloned cDNAs representing the entire, homologous (80%) translated sequences of human phosphoribosylpyrophosphate synthetase (PRS) 1 and PRS 2 cDNAs were utilized as probes to localize the corresponding human PRPS1 and PRPS2 genes, previously reported to be X chromosome linked. PRPS1 and PRPS2 loci mapped to the intervals Xq22-q24 and Xp22.2-p22.3, respectively, using a combination of in situ chromosomal hybridization and human x rodent somatic cell panel genomic DNA hybridization analyses. A PRPS1-related gene or pseudogene (PRPS1L2) was also identified using in situ chromosomal hybridization at 9q33-q34. Human HPRT and PRPS1 loci are not closely linked. Despite marked cDNA and deduced amino acid sequence homology, human PRS 1 and PRS 2 isoforms are encoded by genes widely separated on the X chromosome. 相似文献