Hereditary spastic paraplegia type 35 in a family from Mali
© Published 2019. This article is a U.S. Government work and is in the public domain in the USA..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:179 |
|---|---|
| Enthalten in: |
American journal of medical genetics. Part A - 179(2019), 7 vom: 13. Juli, Seite 1122-1125 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Landouré, Guida [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Africa |
|---|
| Anmerkungen: |
Date Completed 08.06.2020 Date Revised 09.01.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1002/ajmg.a.61179 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM297065491 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM297065491 | ||
| 003 | DE-627 | ||
| 005 | 20231225091206.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/ajmg.a.61179 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0990.xml |
| 035 | |a (DE-627)NLM297065491 | ||
| 035 | |a (NLM)31087769 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Landouré, Guida |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Hereditary spastic paraplegia type 35 in a family from Mali |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 08.06.2020 | ||
| 500 | |a Date Revised 09.01.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © Published 2019. This article is a U.S. Government work and is in the public domain in the USA. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Case Reports | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a FA2H variant | |
| 650 | 4 | |a Africa | |
| 650 | 4 | |a Mali | |
| 650 | 4 | |a SPG35 | |
| 650 | 4 | |a genetic epidemiology | |
| 650 | 7 | |a Mixed Function Oxygenases |2 NLM | |
| 650 | 7 | |a EC 1.- |2 NLM | |
| 650 | 7 | |a fatty acid alpha-hydroxylase |2 NLM | |
| 650 | 7 | |a EC 1.- |2 NLM | |
| 700 | 1 | |a Dembélé, Kékouta |e verfasserin |4 aut | |
| 700 | 1 | |a Cissé, Lassana |e verfasserin |4 aut | |
| 700 | 1 | |a Samassékou, Oumar |e verfasserin |4 aut | |
| 700 | 1 | |a Diarra, Salimata |e verfasserin |4 aut | |
| 700 | 1 | |a Bocoum, Abdoulaye |e verfasserin |4 aut | |
| 700 | 1 | |a Dembélé, Mohamede E |e verfasserin |4 aut | |
| 700 | 1 | |a Fischbeck, Kenneth H |e verfasserin |4 aut | |
| 700 | 1 | |a Guinto, Cheick O |e verfasserin |4 aut | |
| 700 | 0 | |a from The H3Africa Consortium |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t American journal of medical genetics. Part A |d 2003 |g 179(2019), 7 vom: 13. Juli, Seite 1122-1125 |w (DE-627)NLM122607996 |x 1552-4833 |7 nnns |
| 773 | 1 | 8 | |g volume:179 |g year:2019 |g number:7 |g day:13 |g month:07 |g pages:1122-1125 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/ajmg.a.61179 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 179 |j 2019 |e 7 |b 13 |c 07 |h 1122-1125 | ||