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Hereditary spastic paraplegia type 35 in a family from Mali
Author(s) -
Landouré Guida,
Dembélé Kékouta,
Cissé Lassana,
Samassékou Oumar,
Diarra Salimata,
Bocoum Abdoulaye,
Dembélé Mohamede E.,
Fischbeck Kenneth H.,
Guinto Cheick O.
Publication year - 2019
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61179
Subject(s) - hereditary spastic paraplegia , spasticity , weakness , medicine , population , spastic , paraplegia , family history , genetics , exon , phenotype , biology , physical medicine and rehabilitation , gene , anatomy , psychiatry , cerebral palsy , spinal cord , environmental health
Abstract Variants in FA2H have been associated with a wide range of phenotypes including hereditary spastic paraplegia type 35 (SPG35); however, genetically confirmed cases have not been reported in Africa. We report here the first African family with a variant in the FA2H gene causing SPG35. Four affected siblings with consanguineous parents presented with walking difficulty at age 2–3 and progressive limb weakness. They became wheelchair‐bound 2 years after disease onset. Neurological examination confirmed lower greater than upper limb weakness and atrophy, brisk reflexes throughout, and spasticity with scissor legs. The patients also had choking, urinary urgency, and mental retardation. A brain MRI showed thin corpus callosum and periventricular leucodystrophy. Testing of 58 SPG genes showed a homozygous variant in FA2H at the exon 5 donor site c.786+1G>A, which has previously been shown to cause skipping of exons 5 and 6 of the gene transcript. This variant segregated with the disease in the family. This variant has been reported previously with a similar phenotype and slow progression in a population with different background. Here, we confirm its pathogenicity and expand its genetic epidemiology. Studying diverse populations may help to increase understanding of the disease mechanism and ultimately lead to therapeutic targets.