CYP7B1 mutations in pure and complex forms of hereditary spastic paraplegia type 5

Goizet, Cyril; Boukhris, A.; Dürr, Alexandra; Beetz, Christian; Truchetto, Jérémy; Tesson, Christelle; Tsaousidou, Maria; Forlani, Sylvie; Guyant‐Maréchal, Lucie; Fontaine, Bertrand; Guimarães, João Tiago; Isidor, Bertrand; Chazouillères, Olivier; Wendum, Dominique; Grid, Djamel; Chevy, Françoise; Chinnery, Patrick F.; Coutinho, Paula; Azulay, Jean‐Philippe; Feki, Imed; Mochel, Fanny; Wolf, Claude; Mhiri, Chokri; Crosby, Andrew H.; Brice, Alexis; Stevanin, Giovanni

doi:10.1093/brain/awp073

Cited by 96 publications

(96 citation statements)

References 36 publications

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“…There are several reports in the literature of white matter hyperintensities (diffuse or patchy) and corpus callosum abnormalities in association with HSP. 9,10,17,19,20,[26][27][28][29][30] Thinning of the cervical and thoracic spinal cord has been noted in HSP. 31 Volume loss is an expected finding as there is a degeneration of the longer corticospinal tracts to the spinal cord (mainly to the lower limbs) and dorsal column pathway within the spinal cord.…”

Section: Discussionmentioning

confidence: 99%

Clinical Spectrum of Hereditary Spastic Paraplegia in Children : A Study of 74 Cases = الطيف السريري للشلل السفلي التشنجي الوراثي في الأطفال : دراسة 74 حالة

Koul¹,

Al-Murshedi²,

Al-Azri³

et al. 2013

SQUMJ

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abstract:Objectives: The aim of the study was to explore the spectrum of hereditary spastic paraplegia (HSP) in children in Oman. Methods: This retrospective study was carried out between January 1994 and August 2011 on children with delayed development, gait disorders and motor handicaps, with signs of symmetrical pyramidal tract involvement. A detailed perinatal and family history, including the age of onset of symptoms, was recorded. The children were labelled as having either the pure or complicated form of HSP based on the established diagnostic criteria. In families with more than one affected child, parents and all other siblings were also examined. Results: Within the study, 74 children from 31 families were diagnosed with HSP. Parental consanguinity was seen in 91% of cases, with 44 children (59.4%) experiencing onset of the disease under one year of age. Complicated HSP was the most common type, seen in 81.1%. Speech involvement, mental retardation, and epilepsy were the most common associated abnormalities. Nonspecific white matter changes and corpus callosum abnormalities were noted in 24.3% of cases on magnetic resonance imaging. Conclusion: The study described clinical features of 74 children with HSP. Autosomal recessive complicated HSP was seen in 81.1% of cases. Keywords

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Section: Discussionmentioning

confidence: 99%

Clinical Spectrum of Hereditary Spastic Paraplegia in Children : A Study of 74 Cases = الطيف السريري للشلل السفلي التشنجي الوراثي في الأطفال : دراسة 74 حالة

Koul¹,

Al-Murshedi²,

Al-Azri³

et al. 2013

SQUMJ

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“…Age at onset varied from 2 to 39 years old (mean, 13.6 ± 11.4 years) but very early ages at onset were exclusively observed in the family published by Erlich et al 4 The coexistence of pure and complicated profiles within one form of HSP is well known in SPG4, SPG5, SPG7, SPG10, SPG27 and SPG31 patients. 13,[16][17][18][19][20][21] Several recently discovered ARHSP forms were initially thought to be pure ARHSP without any cerebellar signs or cerebellar atrophy on brain imaging, a view that was subsequently revised after more families were identified. This was the case for SPG7 (paraplegin) and SPG5 (CYB7B1).…”

Section: Spg30 Phenotypementioning

confidence: 99%

KIF1A missense mutations in SPG30, an autosomal recessive spastic paraplegia: distinct phenotypes according to the nature of the mutations

et al. 2012

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The hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurodegenerative diseases characterised by progressive spasticity in the lower limbs. The nosology of autosomal recessive forms is complex as most mapped loci have been identified in only one or a few families and account for only a small percentage of patients. We used next-generation sequencing focused on the SPG30 chromosomal region on chromosome 2q37.3 in two patients from the original linked family. In addition, wide genome scan and candidate gene analysis were performed in a second family of Palestinian origin. We identified a single homozygous mutation, p.R350G, that was found to cosegregate with the disease in the SPG30 kindred and was absent in 970 control chromosomes while affecting a strongly conserved amino acid at the end of the motor domain of KIF1A. Homozygosity and linkage mapping followed by mutation screening of KIF1A allowed us to identify a second mutation, p.A255V, in the second family. Comparison of the clinical features with the nature of the mutations of all reported KIF1A families, including those reported recently with hereditary sensory and autonomic neuropathy, suggests phenotypegenotype correlations that may help to understand the mechanisms involved in motor neuron degeneration. We have shown that mutations in the KIF1A gene are responsible for SPG30 in two autosomal recessive HSP families. In published families, the nature of the KIF1A mutations seems to be of good predictor of the underlying phenotype and vice versa. INTRODUCTIONThe hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurodegenerative diseases characterised by progressive spasticity in the lower limbs. 1 The mode of inheritance may be autosomal dominant, autosomal recessive (ARHSP) or X-linked. More than 48 different loci (SPGn) have been mapped so far, and 23 responsible genes identified. The corresponding proteins are often involved in intracellular trafficking or mitochondrial functions. 2,3 Clinically, one can distinguish between pure and complicated forms of HSP. 1,2 Pure forms consist of isolated pyramidal signs, such as spasticity, abnormal reflexes (brisk reflexes and Babinski sign) and motor deficit, often associated with sphincter disturbances and deep sensory loss. In the complicated forms of HSP the disease is variably associated with numerous combinations of neurological and extraneurological signs, such as cerebellar ataxia, dysarthria, mental retardation, peripheral neuropathy, optic atrophy, retinitis pigmentosa and/or hearing loss, which may be accompanied by abnormal brain MRI (atrophy of the cortex, cerebellum or corpus callosum, white matter abnormalities, etc).Mutations in the KIF1A gene (MIM 601255) were very recently described in two different clinically and genetically heterogeneous groups of neurodegenerative diseases. 4,5 In hereditary sensory and autonomic neuropathy (HSAN), all patients from four families with different origins shared a common hom...

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“…The proband had definite HSP with disease onset at the age of seven, and some sensory involvement and seizures. A homozygous c.1450G>A mutation was previously reported in a Tunisian consanguineous family 2 and as a compound heterozygous state in a French sporadic case 4 . The second case was an unrelated French Canadian family (Figure, Family B), both the HSP proband and her affected brother had compound heterozygous mutations in CYP7B1.…”

Section: Resultsmentioning

confidence: 76%

“…Both the proband and her brother had an allele with a c.825T>A change that translates to a protein truncating nonsense mutation (p.Y275X). Homozygous c.825T>A mutations were previously reported in a Portuguese sporadic HSP case in whom additional features of optic atrophy were noted 4 . The second mutated allele of CYP7B1 was found to be a c.1456C>T change that creates a missense mutation p.R486C in the last exon.…”

Section: Resultsmentioning

confidence: 76%

CYP7B1 Mutations in French-Canadian Hereditary Spastic Paraplegia Subjects

Noreau

Szuto²,

Levert³

et al. 2012

Can. J. Neurol. Sci.

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CYP7B1 mutations in pure and complex forms of hereditary spastic paraplegia type 5

Cited by 96 publications

References 36 publications

Clinical Spectrum of Hereditary Spastic Paraplegia in Children : A Study of 74 Cases = الطيف السريري للشلل السفلي التشنجي الوراثي في الأطفال : دراسة 74 حالة

Clinical Spectrum of Hereditary Spastic Paraplegia in Children : A Study of 74 Cases = الطيف السريري للشلل السفلي التشنجي الوراثي في الأطفال : دراسة 74 حالة

KIF1A missense mutations in SPG30, an autosomal recessive spastic paraplegia: distinct phenotypes according to the nature of the mutations

CYP7B1 Mutations in French-Canadian Hereditary Spastic Paraplegia Subjects

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