An autosomal recessive leucoencephalopathy with ischemic stroke, dysmorphic syndrome and retinitis pigmentosa maps to chromosome 17q24.2-25.3

Ahmed Bouhouche,Jehanne Aasfara,Naima Bouslam,Layachi Chabraoui,Ali Benomar,Sanaa Sefiani,Mohamed Jiddane,Elmostafa El Fahime,Lamiae Lachhab,Leila Errguig,Mohamed Yahyaoui,Abdeljalil El Quessar

doi:10.1186/1471-2350-13-18

Abstract

BackgroundSingle-gene disorders related to ischemic stroke seem to be an important cause of stroke in young patients without known risk factors. To identify new genes responsible of such diseases, we studied a consanguineous Moroccan family with three affected individuals displaying hereditary leucoencephalopathy with ischemic stroke, dysmorphic syndrome and retinitis pigmentosa that appears to segregate in autosomal recessive pattern.MethodsAll family members underwent neurological and radiological examinations. A genome wide search was conducted in this family using the ABI PRISM linkage mapping set version 2.5 from Applied Biosystems. Six candidate genes within the region linked to the disease were screened for mutations by direct sequencing.ResultsEvidence of linkage was obtained on chromosome 17q24.2-25.3. Analysis of recombination events and LOD score calculation suggests linkage of the responsible gene in a genetic interval of 11 Mb located between D17S789 and D17S1806 with a maximal multipoint LOD score of 2.90. Sequencing of seven candidate genes in this locus, ATP5H, FDXR, SLC25A19, MCT8, CYGB, KCNJ16 and GRIN2C, identified three missense mutations in the FDXR gene which were also found in a homozygous state in three healthy controls, suggesting that these variants are not disease-causing mutations in the family.ConclusionA novel locus for leucoencephalopathy with ischemic stroke, dysmorphic syndrome and retinitis pigmentosa has been mapped to chromosome 17q24.2-25.3 in a consanguineous Moroccan family.

Highlights

Single-gene disorders related to ischemic stroke seem to be an important cause of stroke in young patients without known risk factors
Nuclear single-gene disorders related to ischemic stroke are an important cause of stroke, especially in young patients without known risk factors [1]
We report on a consanguineous Moroccan family with three patients displaying an autosomal recessive leucoencephalopathy with ischemic stroke, dysmorphic syndrome and retinitis pigmentosa

Summary

Introduction

Single-gene disorders related to ischemic stroke seem to be an important cause of stroke in young patients without known risk factors. Nuclear single-gene disorders related to ischemic stroke are an important cause of stroke, especially in young patients without known risk factors [1]. These diseases could be associated with different stroke phenotypes including arterial dissection, small vessel, and large vessel which are inherited as dominant, recessive or X linked trait. Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) which is a generalized disease of the small arteries, largely predominating in the brain caused by mutations in NOTCH3 gene [2,3]. The EhlersDanlos syndrome type IV (EDS) is a connective tissue disorder defined by characteristic facial features, translucent skin, easy bruising, and severe arterial, digestive and uterine complications resulting from mutations in COL3A1 gene [6]

Methods

Results

Conclusion