Exome sequencing discloses KALRN homozygous variant as likely cause of intellectual disability and short stature in a consanguineous pedigree

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Serval ID
serval:BIB_AF21F258E20A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Exome sequencing discloses KALRN homozygous variant as likely cause of intellectual disability and short stature in a consanguineous pedigree
Journal
Hum Genomics
Author(s)
Makrythanasis P., Guipponi M., Santoni F. A., Zaki M., Issa M. Y., Ansar M., Hamamy H., Antonarakis S. E.
ISSN
1479-7364 (Electronic)
ISSN-L
1473-9542
Publication state
Published
Issued date
2016
Volume
10
Number
1
Pages
26
Language
english
Notes
Makrythanasis, Periklis
Guipponi, Michel
Santoni, Federico A
Zaki, Maha
Issa, Mahmoud Y
Ansar, Muhammad
Hamamy, Hanan
Antonarakis, Stylianos E
eng
Research Support, Non-U.S. Gov't
England
Hum Genomics. 2016 Jul 16;10(1):26. doi: 10.1186/s40246-016-0082-2.
Abstract
BACKGROUND: The recent availability of whole-exome sequencing has opened new possibilities for the evaluation of individuals with genetically undiagnosed intellectual disability. RESULTS: We report two affected siblings, offspring of first-cousin parents, with intellectual disability, hypotonia, short stature, growth hormone deficiency, and delayed bone age. All members of the nuclear family were genotyped, and exome sequencing was performed in one of the affected individuals. We used an in-house algorithm (CATCH v1.1) that combines homozygosity mapping with exome sequencing results and provides a list of candidate variants. One identified novel homozygous missense variant in KALRN (NM_003947.4:c.3644C>A: p.(Thr1215Lys)) was predicted to be pathogenic by all pathogenicity prediction software used (SIFT, PolyPhen, Mutation Taster). KALRN encodes the protein kalirin, which is a GTP-exchange factor protein with a reported role in cytoskeletal remodeling and dendritic spine formation in neurons. It is known that mice with ablation of Kalrn exhibit age-dependent functional deficits and behavioral phenotypes. CONCLUSION: Exome sequencing provided initial evidence linking KALRN to monogenic intellectual disability in man, and we propose that KALRN is the causative gene for the autosomal recessive phenotype in this family.
Keywords
Adolescent, Child, Consanguinity, DNA Mutational Analysis, Developmental Disabilities/*genetics, Exome/genetics, Female, Genetic Association Studies, Guanine Nucleotide Exchange Factors/*genetics, Homozygote, Humans, Intellectual Disability/*genetics, Male, Mutation, Missense, Protein-Serine-Threonine Kinases/*genetics, *Consanguineous, *Exome sequencing, *Intellectual disability, *kalrn, *Short stature
Pubmed
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20/05/2019 12:52
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13/01/2021 7:10
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