Expanding the clinical and genetic spectra of NKX6-2 -related disorder
Autor: | Hanadi A. Abdelrahman, Arndt Rolfs, Fahad Al-Hakami, L.I. Al-Gazali, Nouriya Al-Sannaa, Aida M. Bertoli-Avella, Peter Bauer, Halenur Yavuz, A.A. Elmonairy, A.M. Al Shamsi, Aiman Shawli, Seham Alameer, Krishna Kumar Kandaswamy, Oliver Brandau, Majid Alfadhel, Khalid Al-Thihli, Caterina Baldi |
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Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine Adolescent Nystagmus 030105 genetics & heredity White matter Genetic Heterogeneity 03 medical and health sciences 0302 clinical medicine Seizures Exome Sequencing Genetics Humans Medicine Exome Genetic Predisposition to Disease Child Genetic Association Studies Genetics (clinical) Homeodomain Proteins Whole Genome Sequencing Genetic heterogeneity business.industry Homozygote Infant White Matter Phenotype Hypotonia Hereditary Central Nervous System Demyelinating Diseases medicine.anatomical_structure Child Preschool Mutation Female Related disorder medicine.symptom business Psychomotor delay Developmental regression 030217 neurology & neurosurgery |
Zdroj: | Clinical Genetics. 93:1087-1092 |
ISSN: | 0009-9163 |
Popis: | Hypomyelinating leukodystrophies (HLDs) affect the white matter of the central nervous system and manifest as neurological disorders. They are genetically heterogeneous. Very recently, biallelic variants in NKX6-2 have been suggested to cause a novel form of autosomal recessive HLD. Using whole-exome or whole-genome sequencing, we identified the previously reported c.196delC and c.487C>G variants in NKX6-2 in 3 and 2 unrelated index cases, respectively; the novel c.608G>A variant was identified in a sixth patient. All variants were homozygous in affected family members only. Our patients share a primary diagnosis of psychomotor delay, and they show spastic quadriparesis, nystagmus and hypotonia. Seizures and dysmorphic features (observed in 2 families each) represent an addition to the phenotype, while developmental regression (observed in 3 families) appears to be a notable and previously underestimated clinical feature. Our findings extend the clinical and mutational spectra associated with this novel form of HLD. Comparative analysis of our 10 patients and the 15 reported previously did, however, not reveal clear evidence for a genotype-phenotype correlation. |
Databáze: | OpenAIRE |
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