{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T16:34:41Z","timestamp":1772814881460,"version":"3.50.1"},"reference-count":40,"publisher":"BMJ","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1997,7]]},"abstract":"<jats:p>In 1972, Fried described a large Scottish family affected by X linked mental retardation (XLMR), hydrocephalus, and mild facial dysmorphism. The phenotype has considerable similarity to the MASA syndrome, which results from mutations of the L1CAM gene in Xq28, and this family has since been assumed to be an example of this condition. We have reinvestigated the family for linkage to X chromosome markers, and obtained additional clinical information on surviving affected subjects. The phenotype in these patients has evolved into a distinctive syndrome, with severe mental retardation (MR), spastic diplegia, ventricular dilatation, and calcification of the basal ganglia. Linkage to Xq28 markers has been excluded, suggesting that Fried syndrome is not allelic with MASA syndrome. Two point and multipoint linkage analysis indicates that the gene for this condition lies within the interval KAL-DXS989 in Xp22. We propose the designation Fried syndrome to emphasise the disorder's distinctive phenotype.<\/jats:p>","DOI":"10.1136\/jmg.34.7.535","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"535-540","source":"Crossref","is-referenced-by-count":23,"title":["Fried syndrome is a distinct X linked mental retardation syndrome mapping to Xp22."],"prefix":"10.1136","volume":"34","author":[{"given":"L","family":"Strain","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A F","family":"Wright","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D T","family":"Bonthron","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1997,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/j.1399-0004.1972.tb04274.x","article-title":"X-linked mental retardation and\/or hydrocephalus","volume":"3","author":"Fried, K.","year":"1972","unstructured":"Fried K. 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Hum Genet 1989;82:367-70.","journal-title":"Hum Genet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/ng0794-402","article-title":"X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the LI gene","volume":"7","author":"Jouet, M.; Rosenthal, A.; Armstrong, G.","year":"1994","unstructured":"Jouet M, Rosenthal A, Armstrong G, et al. X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the LI gene. Nat Genet 1994;7:402-7.","journal-title":"Nat Genet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1136\/jmg.10.1.17","article-title":"Possible linkage between Xg and the locus for a gene causing mental retardation with or without hydrocephalus","volume":"10","author":"Fried, K.; Sanger, R.","year":"1973","unstructured":"Fried K, Sanger R. Possible linkage between Xg and the locus for a gene causing mental retardation with or without hydrocephalus. Med Genet 1973; 10: 17-18.","journal-title":"Med Genet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/0888-7543(90)90294-5","article-title":"Assignment of X-linked hydrocephalus to Xq28 by linkage analysis","volume":"8","author":"Willems, P.J.; Dijkstra, I.; Van der Auwera, B.J.","year":"1990","unstructured":"Willems PJ, Dijkstra I, Van der Auwera BJ, et al. Assignment of X-linked hydrocephalus to Xq28 by linkage analysis. Genomics 1990;8:367-70.","journal-title":"Genomics"},{"key":"ref_7","article-title":"The London Dysmorphology Database. Version 1.2","author":"Winter, R.; Baraitser, M.","year":"1995","unstructured":"Winter R, Baraitser M. The London Dysmorphology Database. Version 1.2. Oxford: Oxford University Press, 1995."},{"key":"ref_8","first-page":"59","article-title":"X linked hydrocephalus and MASA syndrome","volume":"33","author":"Kenwrick, S.; Jouet, M.; Donnai, D.","year":"1996","unstructured":"Kenwrick S, Jouet M, Donnai D. X linked hydrocephalus and MASA syndrome. J7Med Genet 1996;33:59-65."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1111\/j.1399-0004.1992.tb03150.x","article-title":"MASA syndrome","volume":"42","author":"Schrander-Stumpel, C.; Fryns, J.P.","year":"1992","unstructured":"Schrander-Stumpel C, Fryns JP. MASA syndrome. Clin Genet 1992;42: 102-3.","journal-title":"Clin Genet"},{"key":"ref_10","first-page":"10716","article-title":"Spectrum of X-linked hydrocephalus (HSAS), MASA syndrome, and complicated spastic paraplegia (SPG1) - clinical review with 6 additional families","volume":"57","author":"Schrander-Stumpel, C.; Howeler, C.; Jones, M.","year":"1995","unstructured":"Schrander-Stumpel C, Howeler C, Jones M, et al. Spectrum of X-linked hydrocephalus (HSAS), MASA syndrome, and complicated spastic paraplegia (SPG1) - clinical review with 6 additional families. Am Med Genet 1995;57:10716.","journal-title":"Am Med Genet"},{"key":"ref_11","first-page":"307","article-title":"Further localization of X-linked hydrocephalus in the chromosomal region Xq28","volume":"51","author":"Willems, P.J.; Vits, L.; Raeymaekers, P.","year":"1992","unstructured":"Willems PJ, Vits L, Raeymaekers P, et al. Further localization of X-linked hydrocephalus in the chromosomal region Xq28. Am Hum Genet 1992;51:307-15.","journal-title":"Am Hum Genet"},{"key":"ref_12","first-page":"246339","article-title":"The 1993-94 Genethon human genetic linkage map","volume":"7","author":"Gyapay, G.; Morissette, J.; Vignal, A.","year":"1994","unstructured":"Gyapay G, Morissette J, Vignal A, et al. The 1993-94 Genethon human genetic linkage map. Nat Genet 1994;7:246339.","journal-title":"Nat Genet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/ajmg.1320430140","article-title":"Characterization of new PCR based markers for mapping and diagnosis: AC dinucleotide repeat markers at the DXS237 (GMGX9) and DXS102 (cX38.1) loci","volume":"43","author":"Gedeon, A.K.; Holman, K.; Richards, R.I.; Mulley, J.C.","year":"1992","unstructured":"Gedeon AK, Holman K, Richards RI, Mulley JC. Characterization of new PCR based markers for mapping and diagnosis: AC dinucleotide repeat markers at the DXS237 (GMGX9) and DXS102 (cX38.1) loci. Am J7Med Genet 1992;43:255-60.","journal-title":"Am J7Med Genet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5453","DOI":"10.1093\/nar\/19.19.5453","article-title":"A dinucleotide repeat polymorphism at the Kallmann locus (Xp22.3)","volume":"19","author":"Bouloux, P.M.G.; Hardelin, J.P.; Munroe, P.","year":"1991","unstructured":"Bouloux PMG, Hardelin JP, Munroe P, et al. A dinucleotide repeat polymorphism at the Kallmann locus (Xp22.3). Nucleic Acids Res 1991;19:5453.","journal-title":"Nucleic Acids Res"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1136\/jmg.30.4.300","article-title":"Characterisation of a highly polymorphic microsatellite at the DXS207 locus. Confirmation of a very close linkage to the retinoschisis disease gene","volume":"30","author":"Oudet, C.; Weber, C.; Kaplan, J.","year":"1992","unstructured":"Oudet C, Weber C, Kaplan J, et al. Characterisation of a highly polymorphic microsatellite at the DXS207 locus. 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Am Hum Genet 1991;48:621-7.","journal-title":"Am Hum Genet"},{"key":"ref_20","first-page":"935","article-title":"Localization of the microsatellite probe DXS426 between DXS7 and DXS255 on Xp and linkage to X-linked retinitis pigmentosa","volume":"47","author":"Coleman, M.; Bhattacharya, S.; Lindsay, S.","year":"1990","unstructured":"Coleman M, Bhattacharya S, Lindsay S, et al. Localization of the microsatellite probe DXS426 between DXS7 and DXS255 on Xp and linkage to X-linked retinitis pigmentosa. Am JHum Genet 1990;47:935-40.","journal-title":"Am JHum Genet"},{"key":"ref_21","first-page":"1427","article-title":"Trinucleotide repeat polymorphism in the androgen receptor gene (AR)","volume":"20","author":"Sleddens, H.F.B.M.; Oostra, B.A.; Brinkmann, A.O.; Trapman, J.","year":"1992","unstructured":"Sleddens HFBM, Oostra BA, Brinkmann AO, Trapman J. Trinucleotide repeat polymorphism in the androgen receptor gene (AR). Nucleic Acids Res 1992;20:1427.","journal-title":"Nucleic Acids Res"},{"key":"ref_22","first-page":"4793","article-title":"Polymorphic dinucleotide repeat at the DXS3 locus","volume":"19","author":"Stanier, P.; Newton, R.; Forbes, S.A.; Ivens, A.; Moore, G.E.","year":"1991","unstructured":"Stanier P, Newton R, Forbes SA, Ivens A, Moore GE. Polymorphic dinucleotide repeat at the DXS3 locus. Nucleic Acids Res 1991;19:4793.","journal-title":"Nucleic Acids Res"},{"key":"ref_23","first-page":"37","article-title":"Genetic mapping of new RFLPs at Xq27-q28","volume-title":"Genomics","volume":"9","author":"Suthers, G.K.; Oberle, I.; Nancarrow, J.","year":"1991","unstructured":"Suthers GK, Oberle I, Nancarrow J, et al. Genetic mapping of new RFLPs at Xq27-q28. Genomics 1991;9:37-43."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/0092-8674(91)90283-5","article-title":"Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox","volume":"67","author":"Fu, Y.H.; Kuhl, D.P.A.; Pizzuti, A.","year":"1991","unstructured":"Fu YH, Kuhl DPA, Pizzuti A, et al. Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell 1991;67: 1047-58.","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1126\/science.2573953","article-title":"A new DNA marker tightly linked to the fragile X locus (FRAXA)","volume":"246","author":"Suthers, G.K.; Callen, D.F.; Hyland, V.J.","year":"1989","unstructured":"Suthers GK, Callen DF, Hyland VJ, et al. A new DNA marker tightly linked to the fragile X locus (FRAXA). Science 1989;246: 1298-300.","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/BF00288280","article-title":"A new polymorphic marker very closely linked to DXS52 in the q28 region of the human X chromosome","volume":"82","author":"Vincent, A.; Kretz, C.; Oberle, I.; Mandel, J.L.","year":"1989","unstructured":"Vincent A, Kretz C, Oberle I, Mandel JL. A new polymorphic marker very closely linked to DXS52 in the q28 region of the human X chromosome. Hum Genet 1989;82:85-6.","journal-title":"Hum Genet"},{"issue":"207-1","key":"ref_27","first-page":"1","article-title":"Haemophilia A diagnosis by analysis of a hypervariable dinucleotide repeat within the factor VIII gene","volume":"338","author":"Lalloz, M.R.A.; McVey, J.H.; Pattinson, J.K.; Tuddenham, E.G.D.","year":"1991","unstructured":"Lalloz MRA, McVey JH, Pattinson JK, Tuddenham EGD. Haemophilia A diagnosis by analysis of a hypervariable dinucleotide repeat within the factor VIII gene. Lancet 1991;338:207-1 1.","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/j.1365-2141.1990.tb07839.x","article-title":"The utility of a HindIII polymorphism of factor VIII examined by rapid DNA analysis","volume":"76","author":"Graham, J.B.; Kunkel, G.R.; Fowlkes, D.M.; Lord, S.T.","year":"1990","unstructured":"Graham JB, Kunkel GR, Fowlkes DM, Lord ST. The utility of a HindIII polymorphism of factor VIII examined by rapid DNA analysis. BrJ Haematol 1990;76:75-9.","journal-title":"BrJ Haematol"},{"key":"ref_29","first-page":"543","article-title":"Improved DNA markers for efficient analysis of fragile X families","volume":"30","author":"Heilig, R.; Oberle, I.; Arveiler, B.; Hanauer, A.; Vidaud, M.; Mandel, J.L.","year":"1988","unstructured":"Heilig R, Oberle I, Arveiler B, Hanauer A, Vidaud M, Mandel JL. Improved DNA markers for efficient analysis of fragile X families. AmJrMed Genet 1988;30:543-50.","journal-title":"AmJrMed Genet"},{"key":"ref_30","first-page":"460","article-title":"Easy calculations of lod scores and genetic risks on small computers","volume":"36","author":"Lathrop, G.M.; Lalouel, J.M.","year":"1984","unstructured":"Lathrop GM, Lalouel JM. Easy calculations of lod scores and genetic risks on small computers. Am Hum Genet 1984;36:460-5.","journal-title":"Am Hum Genet"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/ng0395-261","article-title":"A 2D crossover-based map of the human X chromosome as a model for map integration","volume":"9","author":"Fain, P.R.; Kort, E.N.; Chance, P.F.","year":"1995","unstructured":"Fain PR, Kort EN, Chance PF, et al. A 2D crossover-based map of the human X chromosome as a model for map integration. Nat Genet 1995;9:261-6.","journal-title":"Nat Genet"},{"key":"ref_32","article-title":"Handbook of human genetic linkage","author":"Terwilliger, J.D.; Ott, J.","year":"1994","unstructured":"Terwilliger JD, Ott J. Handbook of human genetic linkage. Baltimore: Johns Hopkins University Press, 1994."},{"key":"ref_33","article-title":"Analysis of human genetic linkage. Revised edition","author":"Ott, J.","year":"1991","unstructured":"Ott J. Analysis of human genetic linkage. Revised edition. Baltimore: Johns Hopkins University Press, 1991."},{"key":"ref_34","first-page":"332","article-title":"Agenesis of the corpus callosum associated with MASA syndrome","volume":"2","author":"Boyd, E.; Schwartz, C.E.; Schroer, R.J.","year":"1993","unstructured":"Boyd E, Schwartz CE, Schroer RJ, et al. Agenesis of the corpus callosum associated with MASA syndrome. Clin Dysmorphol 1993;2:332-41.","journal-title":"Clin Dysmorphol"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/ng0494-394","article-title":"Cloning of PBDX, an MIC2-related gene that spans the pseudoautosomal boundary on chromosome Xp","volume":"6","author":"Ellis, N.A.; Ye, T.Z.; Patton, S.; German, J.; Goodfellow, P.N.; Weller, P.","year":"1994","unstructured":"Ellis NA, Ye TZ, Patton S, German J, Goodfellow PN, Weller P. Cloning of PBDX, an MIC2-related gene that spans the pseudoautosomal boundary on chromosome Xp. Nat Genet 1994;6:394-9.","journal-title":"Nat Genet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1006\/geno.1994.1435","article-title":"Construction of a high-resolution linkage map for Xp22. 1-p22.2 and refinement of the genetic localization of the Coffin-Lowry syndrome gene","volume":"22","author":"Biancalana, V.; Trivier, E.; Weber, C.","year":"1994","unstructured":"Biancalana V, Trivier E, Weber C, et al. Construction of a high-resolution linkage map for Xp22. 1-p22.2 and refinement of the genetic localization of the Coffin-Lowry syndrome gene. Genomics 1994;22:617-25.","journal-title":"Genomics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1002\/(SICI)1096-8628(19960712)64:1<50::AID-AJMG7>3.0.CO;2-V","article-title":"X-linked mental retardation with thin habitus, osteoporosis, and kyphoscoliosis: linkage to Xp2l.3-p22.12","volume":"64","author":"Arena, J.F.; Schwartz, C.; Ouzts, L.","year":"1996","unstructured":"Arena JF, Schwartz C, Ouzts L, et al. X-linked mental retardation with thin habitus, osteoporosis, and kyphoscoliosis: linkage to Xp2l.3-p22.12. Am JMed Genet 1996;64:50-8.","journal-title":"Am JMed Genet"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/BF01876467","article-title":"Calcified ligamenta flava in a patient with Coffin-Lowry syndrome: biochemical analysis of glycosaminoglycans","volume":"35","author":"Miyazaki, K.; Yamanaka, T.; Ishida, Y.; Oohira, A.","year":"1990","unstructured":"Miyazaki K, Yamanaka T, Ishida Y, Oohira A. Calcified ligamenta flava in a patient with Coffin-Lowry syndrome: biochemical analysis of glycosaminoglycans. Jpn Hum Genet 1990;35:215-21.","journal-title":"Jpn Hum Genet"},{"key":"ref_39","first-page":"14451","article-title":"Coffin-Lowry syndrome associated with calcium pyrophosphate crystal deposition in the ligamenta flava","volume":"275","author":"Ishida, Y.; Oki, T.; Ono, Y.; Nogami, H.","year":"1992","unstructured":"Ishida Y, Oki T, Ono Y, Nogami H. Coffin-Lowry syndrome associated with calcium pyrophosphate crystal deposition in the ligamenta flava. Clin Orthop Rel Res 1992;275:14451.","journal-title":"Clin Orthop Rel Res"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/384567a0","article-title":"Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome","volume":"384","author":"Trivier, E.; De Cesare, D.; Jacquot, S.","year":"1996","unstructured":"Trivier E, De Cesare D, Jacquot S, et al. Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome. 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