case presentation Guida Landour, MD, PhD Department of Neurology - - PowerPoint PPT Presentation

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case presentation Guida Landour, MD, PhD Department of Neurology - - PowerPoint PPT Presentation

Jan 13, 2024 39 likes •189 views

Neurogenetic diseases in Mali: case presentation Guida Landour, MD, PhD Department of Neurology Teaching Hospital of Point G Bamako, Mali Introduction Neurogenetic diseases are neglected - incurable and debilitating - social

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Neurogenetic diseases in Mali: case presentation

Guida Landouré, MD, PhD Department of Neurology Teaching Hospital of Point “G” Bamako, Mali

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Introduction

  • Neurogenetic diseases are neglected
  • incurable and debilitating
  • social factors and limited resources increase this burden
  • raising awareness may lessen the burden
  • Previous studies in Mali
  • Malians favor genetic testing
  • Malians gain knowledge with genetic counseling
  • Novel mutations and gene in 27 families
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Questions

  • Are there new hereditary neurological diseases

entities or variants in Mali?

  • Are these variants due to novel genetic defects
  • r other genetic or environmental factors?
  • Premises
  • Malian have specific phenotypic variants
  • mutations in novel genes or novel mutations in known genes
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Specific aims

  • Specific aim 1
  • Characterize families with hereditary neurological

disorders

  • Specific aim 2
  • Identify mutations causing these diseases and explore their

effect in cell culture models

  • Specific aim 3
  • Train faculty members and students in genetics and

molecular biology

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Methods

  • Patients recruitment
  • patients from our neurology clinic or referred
  • field trips to enroll disabled patients and significant subjects
  • Genetic analysis
  • clinically relevant genes will be tested in some families
  • exome sequencing + linkage analysis
  • variants in mapped regions will be first assessed
  • Cell culture studies and animal models
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Summary

  • 141 families with 486 subjects
  • 485 DNA were collected
  • 224 patients (150 expected for the year)
  • 22 have other diseases
  • Main diseases
  • 29 Spinocerebellar ataxia: SCA2, SCA3, SCA7, unknown
  • 26 Muscular disease
  • 13 Spastic paraplegia
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Spinocerebellar ataxia

  • Autosomal dominant
  • Ataxia, visual and hearing loss
  • Psychiatric symptoms
  • Challenging:
  • father less symptomatic
  • one not showing symptoms
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New Limb-Girdle-Muscular-Dystrophy?

  • Very slow progressive proximal weakness
  • childhood onset but ambulatory at 33 years
  • CK levels normal
  • slight bone deformity in older patients
  • Negative for all muscle genes, SMA, Pompe
  • New gene???

2

* * * * * * * * * * * * * * * * *

2 2

* * *

40 11 58 33 31 28

?

24 9
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Hereditary spastic paraplegia

  • Targeted NextGen panel (all 58 SPG genes)
  • 3 families with novel mutations
  • SPG42: one Chinese family
  • SPG10 and SPG11
  • 4 negative families

<1 23 903 20 16 25 * * 28 32 * 907 909 908 865 IV III II I 11 54 50 30 * * * * ? 9 * * * * * * * * * * * * * * 866 920 904 10 2 V VI 67 46 19 15 16 34 88 9 62 50 22 37 17 48 867 906 916 902 905 913 912 919 917 910 915 911 918

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Spinal muscular atrophy

  • Autosomal recessive and most common severe

inherited disorder of childhood

  • Low carrier frequency in population with African

ancestry: Mali 1/209 (1/25-1/50)

  • Genetic analysis: 0 copies SMN1, 3 copies SMN2
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Challenges

  • Long consent process: low literacy, translation
  • Blood chemistries expensive or unavailable
  • Access to patients in the countryside difficult
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Conclusion/Perspectives

  • Genetic heterogeneity of Malian population
  • Opportunity to consolidate previous finding

and find new genes relevant to other populations

  • Whole exome sequencing and cell studies
  • Reach out to other countries
  • Center for training in neuro- or genetics
  • West African neurogenetic disease survey
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Acknowledgments

University College London, London

  • Robert Kleta
  • Horia Stanescu

GOD and my parents Participating families Neurogenetics Branch/NINDS/NIH

  • Kenneth Fischbeck
  • Christopher Grunseich
  • Alice Schindler
  • Kelian Chen

Teaching Hospital of Point “G”

  • Pr. Traoré M
  • Dr. Fischbeck KH
  • National Institutes of Health
  • Grant#: U01HG007044

Research team

  • Pr. Guinto Cheick O.
  • Pr. Coulibaly Souleymane
  • Pr. Traoré Mahamadou
  • Dr. Sango Hammadoun A.
  • Pr. Youssoufa Maiga
  • Pr. Keita Mohamed
  • Dr. Simaga Assiatou
  • Dr. Ba Hamidou
  • Dr. Samassékou Oumar
  • Dr. Diallo Seybou H.
  • Dr. Coulibaly Thomas
  • Dr. Diallo Salimata
  • Dr. Dramane Coulibaly
  • Dr. Cissé Lassana
  • Diarra Salimata
  • Abdoulaye Yalcouyé
  • Abdoulaye Tamega
  • Kani Aghate Coulibaly
  • Nouhoum Koita
  • Soumaila Niaré