HGNC Approved Gene Symbol: GLRA1
Cytogenetic location: 5q33.1 Genomic coordinates (GRCh38): 5:151,822,513-151,924,851 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 5q33.1 | Hyperekplexia 1 | 149400 | Autosomal dominant; Autosomal recessive | 3 |
The GLRA1 gene encodes the alpha-1 subunit of the glycine receptor, a ligand-gated chloride channel. This inhibitory glycine receptor mediates postsynaptic inhibition in the spinal cord and other regions of the central nervous system. It is a pentameric receptor composed of alpha and beta subunits. (Grenningloh et al., 1990). The GLRB gene (138492) encodes the beta subunit of the receptor.
From a human fetal brain cDNA library, Grenningloh et al. (1990) isolated 2 cDNAs encoding 2 forms of the strychnine-binding subunit of the inhibitory glycine receptor, alpha-1 and alpha-2 (GLRA2; 305990). The predicted 449-amino acid sequence of GLRA1 shows approximately 99% identity to the rat 48-kD polypeptide.
Siren et al. (2006) noted that the GLRA1 gene contains 9 exons.
By radiation hybrid analysis and in situ hybridization, Warrington et al. (1992) and Shiang et al. (1993) mapped the GLRA1 gene to chromosome 5q33-q35. By fluorescence in situ hybridization, Baker et al. (1994) mapped the GLRA1 gene to chromosome 5q32.
Lape et al. (2008) investigated partial agonists for 2 members of the nicotinic superfamily, the muscle nicotinic acetylcholine receptor (100690) and the glycine receptor, and found that the open-shut reaction is similar for both full and partial agonists, but the response to partial agonists is limited by an earlier conformation change (flipping) that takes place when the channel is still shut. Lape et al. (2008) suggested that their observations have implications for the interpretation of structural studies and for the design of partial agonists for therapeutic use.
In Xenopus oocytes and human embryonic kidney cells, Laube et al. (2000) found that low concentrations (10 microM) of extracellular zinc increased both the opening frequency and mean burst duration of the glycine receptor. In contrast, higher levels of zinc (50-500 microM) reduced the open probability of the glycine receptor mainly by decreasing the open frequency and the relative contribution of the longest burst of the single-channel events. Site-directed mutagenesis identified the asp80 and thr112 codons in the GLRA1 gene as important determinants of zinc potentiation and inhibition, respectively. The findings indicated that zinc modulates different steps of the receptor binding and gating cycle via specific allosteric high- and low-affinity binding sites in the extracellular N-terminal region of the GLRA1 subunit.
Hutchinson et al. (2008) reported a 54-year-old man with clinical features of progressive encephalomyelitis with rigidity and myoclonus (PERM; see 184850) associated with serum GLRA1 autoantibodies. There was no evidence of malignancy. The clinical course was progressive, beginning with tingling sensation and spontaneous violent jerks of the limbs and trunk. He later developed ptosis, horizontal gaze palsies, facial weakness, spinal rigidity, and difficulty walking. Aggressive immunosuppressive therapy resulted in significant improvement. The authors noted that mutations in the GLRA1 gene result in hereditary hyperekplexia (149400), which is characterized by excessive startle response. Hutchinson et al. (2008) postulated that anti-GLRA1 antibodies may disrupt glycinergic inhibition in the brainstem and spinal cord.
In 4 different families with autosomal dominant hereditary hyperekplexia-1 (HKPX1; 149400), Shiang et al. (1993) identified 2 different heterozygous point mutations in exon 6 of the GLRA1 gene (138491.0001-138491.0002).
Rees et al. (2001) described an apparently sporadic case of hyperekplexia in an offspring of a consanguineous mating who was homozygous for a mutation in the GLRA1 gene (138491.0003). Thus, human startle disease can display recessive, as well as dominant, inheritance depending on the mutation in GLRA1; this is analogous to the recessive inheritance of the mouse mutant 'spasmodic.'
In a case of recessively inherited hyperekplexia, Brune et al. (1996) found a deletion of exons 1-6 of the GLRA1 gene. Born to consanguineous parents, the affected child was homozygous for this null allele, consistent with complete loss of gene function. The child displayed exaggerated startle responses and pronounced head-retraction jerks reflecting a disinhibition of vestigial brainstem reflexes. In contrast, proprio- and exteroceptive inhibition of muscle activity previously correlated to glycinergic mechanisms were not affected. From studying this patient, the authors concluded that, in contrast to the lethal effect of a null mutation in the recessive mouse mutant 'oscillator' in the Glra1 gene, the loss of the glycine receptor alpha-1 subunit is effectively compensated in man.
Rees et al. (2001) analyzed the GLRA1 gene in 22 unrelated individuals with hyperekplexia and hyperekplexia-related conditions and reported several novel missense mutations and the first nonsense point mutations in GLRA1, most of which were localized outside the regions previously associated with dominant, disease-segregating mutations. The studies corroborated the existence of a recessive form of hyperekplexia. They found that a proportion of sporadic hyperekplexia is accounted for by the homozygous inheritance of recessive GLRA1 mutations or as part of compound heterozygosity.
The mouse mutant phenotype 'spasmodic' (spd) is inherited as a recessive disorder and is phenotypically similar to hyperekplexia, including an altered startle response. The spd gene maps to mouse chromosome 11 in a region that shows extensive syntenic homology to human 5q21-q32. In studies of the lethal neurologic mutant mouse 'oscillator,' Buckwalter et al. (1994) demonstrated that the mutation maps to mouse chromosome 11 and is allelic to 'spasmodic.' They demonstrated that oscillator is caused by a microdeletion in the Glra1 gene. The oscillator deletion causes a frameshift resulting in loss of the highly conserved third cytoplasmic loop and fourth transmembrane domain of the protein.
In mice, Becker et al. (1992) showed that the neonatal Glra2 (305990) subunit is expressed in the first and second postnatal weeks, and is later replaced by the adult Glra1 subunit. This isoform switch is responsible for the relatively later onset of neuromotor symptoms at the end of the second postnatal week in spasmodic and oscillator mice, who have mutant Glra1 subunits.
Hirzel et al. (2006) generated transgenic mice with a homozygous D80A mutation in the Glra1 gene. The substitution selectively eliminates a region in the N-terminal extracellular domain to which zinc binds and potentiates glycine receptor currents at low zinc concentrations. Mutant D80A mice showed a phenotype that was similar to human hyperekplexia, with increased neuromuscular tone, inducible tremor, and abnormal gait. Detailed neurophysiologic studies showed that mutant mice had impaired glycinergic suppression of cone signal transmission and increased response to sudden loud acoustic stimuli. In vitro studies of spinal neurons and brainstem slices showed that the D80A substitution in Glra1 selectively suppressed zinc-mediated potentiation of synaptic inhibitory glycine-receptor currents in the presence of low zinc concentrations compared to wildtype Glra1. Thus, the phenotype in mutant D80A mice specifically resulted from impaired zinc potentiation rather than from a reduction or malfunction of mutant glycine receptors. The findings demonstrated the importance of zinc for proper glycinergic neurotransmission.
In affected members of a large 5-generation family with hereditary hyperekplexia-1 (HKPX1; 149400), originally reported by Ryan et al. (1992), Shiang et al. (1993) identified a heterozygous 1192G-T transversion in exon 6 of the GLRA1 gene, resulting in an arg271-to-leu (R271L) substitution in the extracellular domain adjacent to the second transmembrane domain. The mutation was not found in 50 control individuals.
Rajendra et al. (1994) demonstrated that the R271L mutation causes a significant decrease in the binding affinity for glycine and a decrease in the sensitivity of receptor currents activated by glycine, thus reducing glycinergic inhibitory neurotransmission by producing receptors with diminished agonist responsiveness.
In affected members of 3 families with hyperekplexia-1 (HKPX1; 149400), Shiang et al. (1993) identified a heterozygous 1192G-A transition in exon 6 of the GLRA1 gene, resulting in an arg271-to-gln (R271Q) substitution in the extracellular domain adjacent to the second transmembrane domain. One of the families had previously been reported by Ryan et al. (1992).
Rees et al. (1994) demonstrated the R271Q mutation in affected members of a U.K. family showing autosomal dominant transmission of startle disease.
In a 17-year-old Swiss girl who had had numerous episodes of falling and myoclonia in response to stimuli, Schorderet et al. (1994) identified a heterozygous 1192G-A mutation in the GLRA1 gene. Her older sister and mother also suffered from abnormal startle reflex.
Rajendra et al. (1994) demonstrated that the R271Q mutation causes a significant decrease in the binding affinity for glycine and a decrease in the sensitivity of receptor currents activated by glycine, thus reducing glycinergic inhibitory neurotransmission by producing receptors with diminished agonist responsiveness.
Shiang et al. (1995) reported an additional 5 hyperekplexia families with the 1192G-A mutation. Haplotype analysis suggested that this mutation has arisen at least twice and possibly 4 times.
Elmslie et al. (1996) found the R271Q mutation in 2 of 8 probands with familial hyperekplexia.
In an apparently sporadic case of startle disease (HKPX1; 149400) in the offspring of a consanguineous marriage, Rees et al. (1994) identified homozygosity for a 1112T-A transversion in the GLRA1 gene, resulting in an ile244-to-asn (I244N) substitution. Both parents and 1 asymptomatic sister were heterozygous for the mutation, which was not found in 300 control chromosomes. The 22-year-old patient was 1 of 6 children in a family described as 'Welsh gypsy of Romany origin' who presented with a long history of recurrent injurious falls. She gave a history of excessive startle and repeated falls in response to sudden, unexpected stimuli. She fell with arms held stiffly by her side and had over the years sustained multiple injuries to body, face, head, and knees. No abnormality was detected on MRI scan. Treated with clonazepam, 4 mg daily, she had no more falls and could walk up and down stairs and outside on her own. The phenotype was indistinguishable from that of dominant hyperekplexia.
In 2 families segregating autosomal dominant hyperekplexia (HKPX1; 149400), Shiang et al. (1995) identified a tyr279-to-cys (Y279C) substitution.
In an Italian family with hereditary hyperekplexia (HKPX1; 149400), Milani et al. (1996) identified a mutation in the GLRA1 gene, resulting in a gln266-to-his (Q266H) amino acid substitution.
In a family in which affected members over 4 generations had both hyperekplexia (HKPX1; 149400) and spastic paraparesis, Elmslie et al. (1996) identified a heterozygous 1206A-G transition in exon 6 of the GLRA1 gene, resulting in a lys276-to-glu (K276E) substitution.
In a family from the northeast of Italy with autosomal dominant transmission of startle disease, Seri et al. (1997) demonstrated heterozygosity for the K276E mutation. They noted that the mutation eliminated a StyI restriction site. The affected members of the Italian family had a classic presentation with neonatal rigidity and exaggerated startle response to acoustic or tactile stimuli.
In a pedigree with dominant transmission of hyperekplexia (HKPX1; 149400), Saul et al. (1999) identified a mutation in the GLRA1 gene, resulting in a pro250-to-thr (P250T) substitution. The mutation was predicted to be in the cytoplasmic loop linking transmembrane regions M1 and M2 of the mature alpha-1 polypeptide. After recombinant expression, homomeric mutant subunit channels showed a strong reduction of maximum whole-cell chloride currents and an altered desensitization, consistent with a prolonged recovery from desensitization.
In a sporadic case of hyperekplexia (HKPX1; 149400), Rees et al. (2001) identified compound heterozygosity for 2 mutations in the GLRA1 gene: maternal transmission of a 1-bp deletion of C from a run of 4 Cs at nucleotides 601-605 in exon 4 of the GLRA1 gene, resulting in a truncated GLRA1 polypeptide, and paternal transmission of an 830A-G transition in exon 5A, resulting in a met147-to-val (M147V) amino acid change (138491.0009). The mutations resulted in an ineffective maternal transcript and a paternal transcript representing the sole contributor of the glycine receptor alpha-1 subunit polypeptides. Electrophysiologic responses were unable to demonstrate differences between wildtype and M147V whole-cell concentration-response curves, indicating that ligand binding and macroscopic ion channel function were not affected by the mutation. It remained, however, that compound heterozygosity of 830A-G and 601delC in this patient was associated with the onset of hyperekplexia, while parental and sib carriers of either mutation were asymptomatic.
For discussion of the met147-to-val (M147V) mutation in the GLRA1 gene that was found in compound heterozygous state in a sporadic case of hyperekplexia (HKPX1; 149400) by Rees et al. (2001), see 138491.0008.
Rees et al. (2001) observed a patient with hyperekplexia (HKPX1; 149400) and homozygosity for a 986C-A transversion in exon 5B of the GLRA1 gene, resulting in a tyr202-to-ter (Y202X) premature stop codon. This was the first reported incidence of a nonsense mutation and the second of a null GLRA1 genotype, the first having been described by Brune et al. (1996) on the basis of a deletion. The Pakistani parents were consanguineous and heterozygous carriers. This family confirmed that, in contrast to the murine model oscillator, the complete loss of human glycine receptor-mediated neurotransmission is not lethal (Buckwalter et al., 1994).
Del Giudice et al. (2001) identified an 1158G-A transition in exon 6 of the GLRA1 gene in an Italian family with hyperekplexia (HKPX1; 149400). The mutation was present in heterozygous state in the index patient, a 12-month-old boy with muscular hypertonia and exaggerated startle response, and in his father who had suffered from abnormal startle responses and 'a sort of rigidity' during early infancy. The mutation resulted in a val260-to-met (V260M) substitution near the center of the highly conserved M2 transmembrane domain of the mature polypeptide. The location suggested a role in altering ion channel properties. The mutation was not found in 150 Italian controls.
In an apparently sporadic case of startle disease (HKPX1; 149400), Humeny et al. (2002) identified homozygosity for a 1073C-G transversion in exon 7 of the GLRA1 gene, leading to a ser231-to-arg (S231R) substitution in transmembrane region TM1. The patient was the 6-year-old son of apparently healthy consanguineous parents of Iranian origin. Both parents and 1 asymptomatic sister were heterozygous for the S231R mutation. The proband presented with nocturnal generalized jerks accompanied by short-windedness and slight trembling from birth, and at age 6 years displayed increased muscle proprioceptive reflexes, exaggerated head retraction jerks, myoclonia, atactic gait disturbances, and mild mental retardation. Functional analysis by immunoblotting demonstrated a marked reduction of receptor expression in membrane fractions from cells transfected with the mutant compared to wildtype, and cells transfected with the mutant plasmid displayed a strong reduction of the maximal current. Confocal laser scanning microscopy of transfected cells showed predominant localization in the plasma membrane of wildtype receptors, whereas mutant receptors were mostly distributed intracellularly. The observations suggested that the recessive phenotype may be a consequence of a dramatic loss of functional receptor in the homozygous state.
In affected members of 2 consanguineous Turkish Kurd families with hyperekplexia (HKPX1; 149400), Siren et al. (2006) identified a homozygous 170-kb deletion, beginning 93 kb upstream of the start codon of the GLRA1 gene and including exons 1 to 7. The deletion breakpoints were determined to be the same as that reported by Gilbert et al. (2004) in another affected Turkish Kurd family. Siren et al. (2006) suggested a founder effect.
In a boy with hyperekplexia (HKPX1; 149400), Bellini et al. (2007) identified a de novo 1267C-A transversion in exon 7 of the GLRA1 gene, resulting in a ser296-to-ter (S296X) substitution in the transmembrane 3 domain. Functional expression studies in HEK293 cells showed that the mutant protein failed to elicit chloride currents. Coexpression with the wildtype protein resulted in smaller currents, indicating a dominant-negative effect of the mutant protein. The findings indicated that the mutant protein is expressed and leaves the endoplasmic reticulum, but interacts with normal subunits to suppress normal GLRA1 channel function.
In a father and son with hyperekplexia (HKPX1; 149400), Becker et al. (2008) identified a heterozygous 1180G-A transition in exon 7 of the GLRA1 gene, resulting in a ser267-to-asn (S267N) substitution in transmembrane-2, close to the extracellular opening of the glycine channel. The son had onset shortly after birth, whereas the father had a milder phenotype with later onset. In vitro functional expression studies showed that the mutant channel had similar maximum currents as the wildtype channel, but significantly decreased affinity for glycine. Glycine affinity was reduced about 2.3-fold in cells cotransfected with the mutant and wildtype channels. Tests with other agonists, including taurine and alanine, also showed decreased binding to the mutant channel, resulting in the conversion of these agonists to functional antagonists. There was also decreased modulation of the mutant channel by ethanol.
Baker, E., Sutherland, G. R., Schofield, P. R. Localization of the glycine receptor alpha-1 subunit gene (GLRA1) to chromosome 5q32 by FISH. Genomics 22: 491-493, 1994. [PubMed: 7806244] [Full Text: https://doi.org/10.1006/geno.1994.1419]
Becker, C.-M., Schmieden, V., Tarroni, P., Strasser, U., Betz, H. Isoform-selective deficit of glycine receptors in the mouse mutant spastic. Neuron 8: 283-289, 1992. [PubMed: 1371219] [Full Text: https://doi.org/10.1016/0896-6273(92)90295-o]
Becker, K., Breitinger, H.-G., Humeny, A., Meinck, H.-M., Dietz, B., Aksu, F., Becker, C.-M. The novel hyperekplexia allele GLRA1(S267N) affects the ethanol site of the glycine receptor. Europ. J. Hum. Genet. 16: 223-228, 2008. [PubMed: 18043720] [Full Text: https://doi.org/10.1038/sj.ejhg.5201958]
Bellini, G., Miceli, F., Mangano, S., Miraglia del Giudice, E., Coppola, G., Barbagallo, A., Taglialatela, M., Pascotto, A. Hyperekplexia caused by dominant-negative suppression of GLYRA1 (sic) function. Neurology 68: 1947-1949, 2007. [PubMed: 17536053] [Full Text: https://doi.org/10.1212/01.wnl.0000263193.75291.85]
Brune, W., Weber, R. G., Saul, B., von Knebel Doeberitz, M., Grond-Ginsbach, C., Kellermann, K., Meinck, H.-M., Becker, C.-M. A GLRA1 null mutation in recessive hyperekplexia challenges the functional role of glycine receptors. Am. J. Hum. Genet. 58: 989-997, 1996. [PubMed: 8651283]
Buckwalter, M. S., Cook, S. A., Davisson, M. T., White, W. F., Camper, S. A. A frameshift mutation in the mouse alpha-1 glycine receptor gene (Glra1) results in progressive neurological symptoms and juvenile death. Hum. Molec. Genet. 3: 2025-2030, 1994. [PubMed: 7874121] [Full Text: https://doi.org/10.1093/hmg/3.11.2025]
del Giudice, E. M., Coppola, G., Bellini, G., Cirillo, G., Scuccimarra, G., Pascotto, A. A mutation (V260M) in the middle of the M2 pore-lining domain of the glycine receptor causes hereditary hyperekplexia. Europ. J. Hum. Genet. 9: 873-876, 2001. [PubMed: 11781706] [Full Text: https://doi.org/10.1038/sj.ejhg.5200729]
Elmslie, F. V., Hutchings, S. M., Spencer, V., Curtis, A., Covanis, T., Gardiner, R. M., Rees, M. Analysis of GLRA1 in hereditary and sporadic hyperekplexia: a novel mutation in a family cosegregating for hyperekplexia and spastic paraparesis. J. Med. Genet. 33: 435-436, 1996. [PubMed: 8733061] [Full Text: https://doi.org/10.1136/jmg.33.5.435]
Gilbert, S. L., Ozdag, F., Ulas, U. H., Dobyns, W. B., Lahn, B. T. Hereditary hyperekplexia caused by novel mutations of GLRA1 in Turkish families. Molec. Diag. 8: 151-155, 2004. [PubMed: 15771552] [Full Text: https://doi.org/10.1007/BF03260058]
Grenningloh, G., Schmieden, V., Schofield, P. R., Seeburg, P. H., Siddique, T., Mohandas, T. K., Becker, C.-M., Betz, H. Alpha subunit variants of the human glycine receptor: primary structures, functional expression and chromosomal localization of the corresponding genes. EMBO J. 9: 771-776, 1990. [PubMed: 2155780] [Full Text: https://doi.org/10.1002/j.1460-2075.1990.tb08172.x]
Hirzel, K., Muller, U., Latal, A. T., Hulsmann, S., Grudzinska, J., Seeliger, M. W., Betz, H., Laube, B. Hyperekplexia phenotype of glycine receptor alpha-1 subunit mutant mice identifies Zn(2+) as an essential endogenous modulator of glycinergic neurotransmission. Neuron 52: 679-690, 2006. [PubMed: 17114051] [Full Text: https://doi.org/10.1016/j.neuron.2006.09.035]
Humeny, A., Bonk, T., Becker, K., Jafari-Boroujerdi, M., Stephani, U., Reuter, K., Becker, C.-M. A novel recessive hyperekplexia allele GLRA1 (S231R): genotyping by MALDI-TOF mass spectrometry and functional characterisation as a determinant of cellular glycine receptor trafficking. Europ. J. Hum. Genet. 10: 188-196, 2002. [PubMed: 11973623] [Full Text: https://doi.org/10.1038/sj.ejhg.5200779]
Hutchinson, M., Waters, P., McHugh, J., Gorman, G., O'Riordan, S., Connolly, S., Hager, H., Yu, P., Becker, C.-M., Vincent, A. Progressive encephalomyelitis, rigidity, and myoclonus: a novel glycine receptor antibody. Neurology 71: 1291-1292, 2008. [PubMed: 18852446] [Full Text: https://doi.org/10.1212/01.wnl.0000327606.50322.f0]
Lape, R., Colquhoun, D., Sivilotti, L. G. On the nature of partial agonism in the nicotinic receptor superfamily. Nature 454: 722-727, 2008. [PubMed: 18633353] [Full Text: https://doi.org/10.1038/nature07139]
Laube, B., Kuhse, J., Betz, H. Kinetic and mutational analysis of Zn(2+) modulation of recombinant human inhibitory glycine receptors. J. Physiol. 522: 215-230, 2000. [PubMed: 10639099] [Full Text: https://doi.org/10.1111/j.1469-7793.2000.t01-1-00215.x]
Milani, N., Dalpra, L., del Prete, A., Zanini, R., Larizza, L. A novel mutation (gln266-to-his) in the alpha1 subunit of the inhibitory glycine-receptor gene (GLRA1) in hereditary hyperekplexia. (Letter) Am. J. Hum. Genet. 58: 420-422, 1996. [PubMed: 8571969]
Rajendra, S., Lynch, J. W., Pierce, K. D., French, C. R., Barry, P. H., Schofield, P. R. Startle disease mutations reduce the agonist sensitivity of the human inhibitory glycine receptor. J. Biol. Chem. 269: 18739-18742, 1994. [PubMed: 7518444]
Rees, M. I., Andrew, M., Jawad, S., Owen, M. J. Evidence for recessive as well as dominant forms of startle disease (hyperekplexia) caused by mutations in the alpha-1 subunit of the inhibitory glycine receptor. Hum. Molec. Genet. 3: 2175-2179, 1994. [PubMed: 7881416] [Full Text: https://doi.org/10.1093/hmg/3.12.2175]
Rees, M. I., Lewis, T. M., Vafa, B., Ferrie, C., Corry, P., Muntoni, F., Jungbluth, H., Stephenson, J. B. P., Kerr, M., Snell, R. G., Schofield, P. R., Owen, M. J. Compound heterozygosity and nonsense mutations in the alpha-1-subunit of the inhibitory glycine receptor in hyperekplexia. Hum. Genet. 109: 267-270, 2001. [PubMed: 11702206] [Full Text: https://doi.org/10.1007/s004390100569]
Ryan, S. G., Dixon, M. J., Nigro, M. A., Kelts, K. A., Markand, O. N., Terry, J. C., Shiang, R., Wasmuth, J. J., O'Connell, P. Genetic and radiation hybrid mapping of the hyperekplexia region on chromosome 5q. Am. J. Hum. Genet. 51: 1334-1343, 1992. [PubMed: 1334371]
Saul, B., Kuner, T., Sobetzko, D., Brune, W., Hanefeld, F., Meinck, H.-M., Becker, C.-M. Novel GLRA1 missense mutation (P250T) in dominant hyperekplexia defines an intracellular determinant of glycine receptor channel gating. J. Neurosci. 19: 869-877, 1999. [PubMed: 9920650] [Full Text: https://doi.org/10.1523/JNEUROSCI.19-03-00869.1999]
Schorderet, D. F., Pescia, G., Bernasconi, A., Regli, F. An additional family with startle disease and a G1192A mutation at the alpha-1 subunit of the inhibitory glycine receptor gene. Hum. Molec. Genet. 3: 1201, 1994. [PubMed: 7981700] [Full Text: https://doi.org/10.1093/hmg/3.7.1201]
Seri, M., Bolino, A., Galietta, L. J. V., Lerone, M., Silengo, M., Romeo, G. Startle disease in an Italian family by mutation (K276E): the alpha-subunit of the inhibiting glycine receptor. Hum. Mutat. 9: 185-187, 1997. [PubMed: 9067762] [Full Text: https://doi.org/10.1002/(SICI)1098-1004(1997)9:2<185::AID-HUMU14>3.0.CO;2-Z]
Shiang, R., Ryan, S. G., Zhu, Y.-Z., Fielder, T. J., Allen, R. J., Fryer, A., Yamashita, S., O'Connell, P., Wasmuth, J. J. Mutational analysis of familial and sporadic hyperekplexia. Ann. Neurol. 38: 85-91, 1995. [PubMed: 7611730] [Full Text: https://doi.org/10.1002/ana.410380115]
Shiang, R., Ryan, S. G., Zhu, Y.-Z., Hahn, A. F., O'Connell, P., Wasmuth, J. J. Mutations in the alpha-1 subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia. Nature Genet. 5: 351-357, 1993. [PubMed: 8298642] [Full Text: https://doi.org/10.1038/ng1293-351]
Siren, A., Legros, B., Chahine, L., Misson, J.-P., Pandolfo, M. Hyperekplexia in Kurdish families: a possible GLRA1 founder mutation. Neurology 67: 137-139, 2006. [PubMed: 16832093] [Full Text: https://doi.org/10.1212/01.wnl.0000223347.73493.af]
Warrington, J. A., Bengtsson, U., Bailey, S. K., Lovett, M., Wasmuth, J. J. A comparison of three methods to produce a high resolution physical map of 11 genes on the distal region of the long arm of human electrophoresis and fluorescent in situ hybridization. (Abstract) Am. J. Hum. Genet. 51 (suppl.): A248, 1992.