Publications by authors named "D M LaCombe"
Purpose: Heterozygous pathogenic variants in SPAST are known to cause Hereditary Spastic Paraplegia 4 (SPG4), the most common form of HSP, characterized by progressive bilateral lower limbs spasticity with frequent sphincter disorders. However, there are very few descriptions in the literature of patients carrying biallelic variants in SPAST.
Methods: Targeted Sanger sequencing, panel sequencing and exome sequencing were used to identify the genetic causes in 9 patients from 6 unrelated families with symptoms of HSP or infantile neurodegenerative disorder.
Rubinstein-Taybi syndrome (RTS) is a rare and severe genetic developmental disorder characterized by multiple congenital anomalies and intellectual disability. CREBBP and EP300, the two genes known to cause RTS encode transcriptional coactivators with a catalytic lysine acetyltransferase (KAT) activity. Loss of CBP or p300 function results in a deficit in protein acetylation, in particular at histones.
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- PTEN hamartoma tumour syndrome (PHTS) includes syndromes like Cowden syndrome, with missense variants making up 30% of PHTS cases, yet their classification is complex.
- A study from the Bergonie Institute identified 76 non-truncating variants in 166 patients, developing a new classification method using criteria like functional analysis, phenotypic features, and familial patterns.
- The new approach successfully reclassifies 25 variants, revealing the need to update current classification standards based on multiple factors, and it requires further validation in future research.