Titre
KIF1A novel frameshift variant p.(Ser887Profs*64) exhibits clinical heterogeneity in a Pakistani family with hereditary sensory and autonomic neuropathy type IIC.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Ghafoor, S.
Auteure/Auteur
Rafiq, M.A.
Auteure/Auteur
Abbas Shah, S.T.
Auteure/Auteur
Ansar, M.
Auteure/Auteur
Paton, T.
Auteure/Auteur
Ajmal, M.
Auteure/Auteur
Agha, Z.
Auteure/Auteur
Qamar, R.
Auteure/Auteur
Azam, M.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1563-5279
Statut éditorial
Publié
Date de publication
2024-06
Volume
134
Numéro
6
Première page
665
Dernière page/numéro d’article
675
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Case Reports
Publication Status: ppublish
Publication Status: ppublish
Résumé
Background: Hereditary sensory and autonomic neuropathies (HSANs) are rare heterogeneous group of neurological disorders caused by peripheral nerve deterioration. The HSANs sub-clinical classes have clinical and genetic overlap which often lead to misdiagnosis. In the present study a Pakistani family with five affected members suffering from severe neuropathy were genetically analyzed to identify the disease causative element in the family. Methods: Genome wide high-density single nucleotide polymorphism (SNP) microarray analysis was carried out followed by whole exome sequencing of the affected proband and another affected sibling. Shared homozygous regions in all severely affected members were identified through homozygosity mapping approach. Results: The largest homozygous region of 14.1 Mb shared by the five severely affected members of the family was identified on chromosome 2. Subsequent exome sequencing identified a novel single nucleotide deletion c.2658del; p.(Ser887Profs*64) in KIF1A. Segregation analysis revealed that this mutation was homozygous in all five affected individuals of the family with severe clinical manifestation, while members of the family that were heterozygous carriers shared abnormal skin features (scaly skin) only with the homozygous affected members. Conclusions: A novel frameshift mutation p.(Ser887Profs*64) in KIF1A is the potential cause of severe HSANIIC in a Pakistani family along with incomplete penetrance in mutation carriers. We demonstrate that using a combination of different techniques not only strengthens the gene finding approach but also helps in proper sub-clinical characterization along with identification of mutated alleles exhibiting incomplete penetrance leading to intrafamilial clinical variability in HSAN group of inherited diseases.
PID Serval
serval:BIB_D055B7C2568B
PMID
Date de création
2022-11-02T07:27:28.260Z
Date de création dans IRIS
2025-05-21T00:22:32Z