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. 1998 May;62(5):1070–1076. doi: 10.1086/301821

A syndrome of severe mental retardation, spasticity, and tapetoretinal degeneration linked to chromosome 15q24.

S J Mitchell 1, D P McHale 1, D A Campbell 1, N J Lench 1, R F Mueller 1, S E Bundey 1, A F Markham 1
PMCID: PMC1377078  PMID: 9545391

Abstract

Nine affected individuals are described from a large extended Pakistani family manifesting a syndrome characterized by a triad of varying degrees of spasticity, severe mental retardation, and visual impairment resulting from tapetoretinal degeneration. In all cases, the parents were at least first cousins, since there was complex consanguinity within the pedigree. The clinical features differ from previously reported syndromes involving pigmentary retinal degeneration and appear to represent a new recessively inherited neurodegenerative condition. Linkage to a 4-5 cM-region between markers D15S211 and D15S152 on 15q24 has been established by autozygosity mapping.

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Selected References

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  1. ALSTROM C. H., HALLGREN B., NILSSON L. B., ASANDER H. Retinal degeneration combined with obesity, diabetes mellitus and neurogenous deafness: a specific syndrome (not hitherto described) distinct from the Laurence-Moon-Bardet-Biedl syndrome: a clinical, endocrinological and genetic examination based on a large pedigree. Acta Psychiatr Neurol Scand Suppl. 1959;129:1–35. [PubMed] [Google Scholar]
  2. Allen A. W., Jr, Moon J. B., Hovland K. R., Minckler D. S. Ocular findings in thoracic-pelvic-phalangeal dystrophy. Arch Ophthalmol. 1979 Mar;97(3):489–492. doi: 10.1001/archopht.1979.01020010239010. [DOI] [PubMed] [Google Scholar]
  3. Amir N., Zlotogora J., Bach G. Mucolipidosis type IV: clinical spectrum and natural history. Pediatrics. 1987 Jun;79(6):953–959. [PubMed] [Google Scholar]
  4. BASSEN F. A., KORNZWEIG A. L. Malformation of the erythrocytes in a case of atypical retinitis pigmentosa. Blood. 1950 Apr;5(4):381–387. [PubMed] [Google Scholar]
  5. Ben Hamida C., Doerflinger N., Belal S., Linder C., Reutenauer L., Dib C., Gyapay G., Vignal A., Le Paslier D., Cohen D. Localization of Friedreich ataxia phenotype with selective vitamin E deficiency to chromosome 8q by homozygosity mapping. Nat Genet. 1993 Oct;5(2):195–200. doi: 10.1038/ng1093-195. [DOI] [PubMed] [Google Scholar]
  6. Boucher B. J., Gibberd F. B. Familial ataxia, hypogonadism and retinal degeneration. Acta Neurol Scand. 1969;45(4):507–510. [PubMed] [Google Scholar]
  7. Eller M. S., Oleksiak M. F., McQuaid T. J., McAfee S. G., Gilchrest B. A. The molecular cloning and expression of two CRABP cDNAs from human skin. Exp Cell Res. 1992 Feb;198(2):328–336. doi: 10.1016/0014-4827(92)90387-n. [DOI] [PubMed] [Google Scholar]
  8. Gerich J. E. Hunter's syndrome: beta-galactosidase deficiency in skin. N Engl J Med. 1969 Apr 10;280(15):799–802. doi: 10.1056/NEJM196904102801502. [DOI] [PubMed] [Google Scholar]
  9. HALLGREN B. Retinitis pigmentosa combined with congenital deafness; with vestibulo-cerebellar ataxia and mental abnormality in a proportion of cases: A clinical and genetico-statistical study. Acta Psychiatr Scand Suppl. 1959;34(138):1–101. [PubMed] [Google Scholar]
  10. Joubert M., Eisenring J. J., Robb J. P., Andermann F. Familial agenesis of the cerebellar vermis. A syndrome of episodic hyperpnea, abnormal eye movements, ataxia, and retardation. Neurology. 1969 Sep;19(9):813–825. doi: 10.1212/wnl.19.9.813. [DOI] [PubMed] [Google Scholar]
  11. Kruglyak L., Daly M. J., Lander E. S. Rapid multipoint linkage analysis of recessive traits in nuclear families, including homozygosity mapping. Am J Hum Genet. 1995 Feb;56(2):519–527. [PMC free article] [PubMed] [Google Scholar]
  12. Lander E. S., Botstein D. Homozygosity mapping: a way to map human recessive traits with the DNA of inbred children. Science. 1987 Jun 19;236(4808):1567–1570. doi: 10.1126/science.2884728. [DOI] [PubMed] [Google Scholar]
  13. Mahloudji M., Chuke P. O. Familial spastic paraplegia with retinal degeneration. Johns Hopkins Med J. 1968 Sep;123(3):142–144. [PubMed] [Google Scholar]
  14. Maw M. A., Kennedy B., Knight A., Bridges R., Roth K. E., Mani E. J., Mukkadan J. K., Nancarrow D., Crabb J. W., Denton M. J. Mutation of the gene encoding cellular retinaldehyde-binding protein in autosomal recessive retinitis pigmentosa. Nat Genet. 1997 Oct;17(2):198–200. doi: 10.1038/ng1097-198. [DOI] [PubMed] [Google Scholar]
  15. Mendez H. M., Paskulin G. A., Vallandro C. The syndrome of retinal pigmentary degeneration, microcephaly, and severe mental retardation (Mirhosseini-Holmes-Walton syndrome): report of two patients. Am J Med Genet. 1985 Oct;22(2):223–228. doi: 10.1002/ajmg.1320220202. [DOI] [PubMed] [Google Scholar]
  16. Mirhosseini S. A., Holmes L. B., Walton D. S. Syndrome of pigmentary retinal degeneration, cataract, microcephaly, and severe mental retardation. J Med Genet. 1972 Jun;9(2):193–196. doi: 10.1136/jmg.9.2.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mitchell S., Bundey S. Symmetry of neurological signs in Pakistani patients with probable inherited spastic cerebral palsy. Clin Genet. 1997 Jan;51(1):7–14. doi: 10.1111/j.1399-0004.1997.tb02406.x. [DOI] [PubMed] [Google Scholar]
  18. Moser A. B., Rasmussen M., Naidu S., Watkins P. A., McGuinness M., Hajra A. K., Chen G., Raymond G., Liu A., Gordon D. Phenotype of patients with peroxisomal disorders subdivided into sixteen complementation groups. J Pediatr. 1995 Jul;127(1):13–22. doi: 10.1016/s0022-3476(95)70250-4. [DOI] [PubMed] [Google Scholar]
  19. Norio R., Raitta C. Are the Mirhosseini-Holmes-Walton syndrome and the Cohen syndrome identical? Am J Med Genet. 1986 Oct;25(2):397–398. doi: 10.1002/ajmg.1320250227. [DOI] [PubMed] [Google Scholar]
  20. Petit C. Genes responsible for human hereditary deafness: symphony of a thousand. Nat Genet. 1996 Dec;14(4):385–391. doi: 10.1038/ng1296-385. [DOI] [PubMed] [Google Scholar]
  21. REFSUM S. Heredopathia atactica polyneuritiformis. J Nerv Ment Dis. 1952 Dec;116(6):1046–1050. doi: 10.1097/00005053-195212000-00051. [DOI] [PubMed] [Google Scholar]
  22. Reed P. W., Davies J. L., Copeman J. B., Bennett S. T., Palmer S. M., Pritchard L. E., Gough S. C., Kawaguchi Y., Cordell H. J., Balfour K. M. Chromosome-specific microsatellite sets for fluorescence-based, semi-automated genome mapping. Nat Genet. 1994 Jul;7(3):390–395. doi: 10.1038/ng0794-390. [DOI] [PubMed] [Google Scholar]
  23. SENIOR B., FRIEDMANN A. I., BRAUDO J. L. Juvenile familial nephropathy with tapetoretinal degeneration. A new oculorenal dystrophy. Am J Ophthalmol. 1961 Nov;52:625–633. doi: 10.1016/0002-9394(61)90147-7. [DOI] [PubMed] [Google Scholar]
  24. Schuler G. D., Boguski M. S., Stewart E. A., Stein L. D., Gyapay G., Rice K., White R. E., Rodriguez-Tomé P., Aggarwal A., Bajorek E. A gene map of the human genome. Science. 1996 Oct 25;274(5287):540–546. [PubMed] [Google Scholar]
  25. Scotto J. M., Hadchouel M., Odievre M., Laudat M. H., Saudubray J. M., Dulac O., Beucler I., Beaune P. Infantile phytanic acid storage disease, a possible variant of Refsum's disease: three cases, including ultrastructural studies of the liver. J Inherit Metab Dis. 1982;5(2):83–90. doi: 10.1007/BF01799998. [DOI] [PubMed] [Google Scholar]
  26. Sjaastad O., Berstad J., Gjesdahl P., Gjessing L. Homocarnosinosis. 2. A familial metabolic disorder associated with spastic paraplegia, progressive mental deficiency, and retinal pigmentation. Acta Neurol Scand. 1976 Apr;53(4):275–290. doi: 10.1111/j.1600-0404.1976.tb04348.x. [DOI] [PubMed] [Google Scholar]
  27. Steinlein O., Tariverdian G., Boll H. U., Vogel F. Tapetoretinal degeneration in brothers with apparent Cohen syndrome: nosology with Mirhosseini-Holmes-Walton syndrome. Am J Med Genet. 1991 Nov 1;41(2):196–200. doi: 10.1002/ajmg.1320410213. [DOI] [PubMed] [Google Scholar]
  28. Stewart R. M. Amentia, Familial Cerebellar Diplegia, and Retinitis Pigmentosa. Proc R Soc Med. 1937 May;30(7):849–850. [PMC free article] [PubMed] [Google Scholar]
  29. Wisneiwski K. E., Kida E., Patxot O. F., Connell F. Variability in the clinical and pathological findings in the neuronal ceroid lipofuscinoses: review of data and observations. Am J Med Genet. 1992 Feb 15;42(4):525–532. doi: 10.1002/ajmg.1320420420. [DOI] [PubMed] [Google Scholar]

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