Dr Heema Patel

Research interests

My research interests include the investigation of neurological disorders in genetically isolated populations, particularly anencephaly, spina bifida and the underlying causes of the hereditary spastic paraplegias (HSPs).

I mapped the first Silver syndrome (OMIM), a dominantly-inherited form of HSP, locus (SPG17) and in collaboration with a group in Austria identified the gene responsible (BSCL2, encoding seipin) for this condition and a form of distal hereditary motor neuropathy [Patel et al. 2001; Windpassinger et al. 2004].

The ‘Windows of Hope’ Amish research project, initiated by Dr Andrew Crosby, has provided samples for the study of a number of neurological conditions, one of which being Troyer syndrome (OMIM), a childhood onset autosomal recessively-inherited form of HSP. Homozygosity mapping led to the identification of a novel gene (SPG20, encoding spartin; GeneReviews) responsible for this disorder and the elucidation of three novel protein domains [Patel et al. 2002; Ciccarelli et al. 2003]. Our subsequent studies have included the subcellular localisation and interactions of spartin using a variety of cell culture techniques such as immunocytochemistry and transfections of neuronal cell lines, and confocal microscopy. These studies directly led to the proposal that defects in subcellular transportation dynamics are an underlying cause of the neurodegenerative process seen in HSP as well as other degenerative diseases of the motor neuron.

As a result of our work, we were a key member of the FP6 European consortium of researchers working toward a common goal of elucidating the cause(s) of HSPs.

Publications

Tsaousidou MK, Ouahchi K, Warner TT, Yang Y, Simpson MA, Laing NG, Wilkinson PA, Madrid RE, Patel H, Hentati F, Patton MA, Hentati A, Lamont PJ, Siddique T, Crosby AH (2007) Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration. Am J Hum Genet 82(2):510-515 PubMed

Robay D, Patel H (joint first author), Simpson MA, Brown N, Crosby AH (2006) Endogenous spartin, mutated in hereditary spastic paraplegia, has a complex subcellular localisation suggesting diverse roles in neurons. Exp Cell Res 312(15):2764-2777 PubMed

Reed JA, Wilkinson PA, Patel H, Simpson MA, Chatonnet A, Robay D, Patton MA, Crosby AH, Warner TT (2005) A novel NIPA1 mutation associated with a pure form of autosomal dominant hereditary spastic paraplegia. Neurogenetics 6(2):79-84 PubMed

Patel H, Crosby A (November 2004) Troyer Syndrome. In: GeneReviews at GeneTests: Medical Genetics Information Resource [database online]. Copyright, University of Washington, Seattle, 1997-2004

Wilkinson PA, Simpson MA, Bastaki L, Patel H, Reed JA, Kalidas K, Samilchuk E, Khan R, Warner TT, Crosby AH (2004) A new locus for autosomal recessive complicated hereditary spastic paraplegia (SPG26) maps to chromosome 12p11.1—12q14. J Med Genet 42(1):80-82 PubMed

Proukakis C, Cross H, Patel H, Patton MA, Valentine A, Crosby AH (2004)Troyer syndrome revisited: A clinical and radiological study of a complicated hereditary spastic paraplegia. J Neurol 251(9):1105-1110 PubMed

Warner T, Patel H, Proukakis C, Reed JA, McKie L, Wills A, Patton MA, Crosby AH (2004) A clinical, genetic and candidate gene study of Silver syndrome, a complicated form of hereditary spastic paraplegia. J Neurol 251(9):1068-1074 PubMed

Windpassinger C, Auer-Grumbach M, Irobi J, Patel H, Petek E, Horl G, Malli R, Reed JA, Dierick I, Verpoorten N, Warner TT, Proukakis C, Van den Bergh P, Verellen C, Van Maldergem L, Merlini L, De Jonghe P, Timmerman V, Crosby AH, Wagner K (2004) Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome. Nat Genet 36(3):271-276 PubMed

Wilkinson PA, Hart PE, Patel H, Warner TT, Crosby AH (2003) SPG3A mutation screening in English families with early onset autosomal hereditary spastic paraplegia. J Neurol Sci 216(1):43-45 PubMed

Wilkinson PA, Crosby AH, Turner C, Patel H, Wood NW, Schapira AH, Warner TT (2003) A clinical and genetic study of SPG5A linked autosomal recessive hereditary spastic paraplegia. Neurology 61(2):235-238 PubMed

Ciccarelli FD, Proukakis C, Patel H, Cross H, Azam S, Patton MA, Bork P, Crosby AH (2003) The identification of a conserved domain in both spartin and spastin, mutated in hereditary spastic paraplegia. Genomics 81(4):437-441 PubMed

Patel H, Cross H, Proukakis C, Hershberger R, Bork P, Ciccarelli FD, Patton MA, McKusick VA, Crosby AH (2002) SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia. Nat Genet 31(4):347-348 PubMed

Patel H, Hart PE, Warner TT, Houlston RS, Patton MA, Jeffery S, Crosby AH (2001) The Silver syndrome variant of hereditary spastic paraplegia maps to chromosome 11q12-q14, with evidence for genetic heterogeneity within this subtype. Am J Hum Genet 69(1):209-215 PubMed

Patel H, Hart PE, Warner T, Allen I, Phillimore HE, Silver JR, Wood NW, Jeffery S, Patton MA and Crosby AH (2001) Silver syndrome is not linked to any of the previously established autosomal dominant hereditary spastic paraplegia loci. Am J Med Genet 102(1):68-72 PubMed

Patel H, Nardelli M, Fenn T, Houlston R, Coonar A, Patton MA, Crosby AH (2001) Homozygosity at chromosome 8qter in individuals affected by mal de Meleda (Meleda disease) originating from the island of Meleda. Br J Dermatol 144(4):731-734 PubMed