Spondyloenchondrodysplasia in five new patients: identification of three novel ACP5 variants with variable neurological presentations.
Mol Genet Genomics
; 298(3): 709-720, 2023 May.
Article
in En
| MEDLINE
| ID: mdl-37010587
ABSTRACT
Spondyloenchondrodysplasia (SPENCD) is an immune-osseous disorder caused by biallelic variants in ACP5 gene and is less commonly associated with neurological abnormalities such as global developmental delay, spasticity and seizures. Herein, we describe five new patients from four unrelated Egyptian families with complex clinical presentations including predominant neurological presentations masking the skeletal and immunological manifestations. All our patients had spasticity with variable associations of motor and mental delay or epilepsy. All except for one patient had bilateral calcification in the basal ganglia. One patient had an associated growth hormone deficiency with fair response to growth hormone therapy (GH) where the height improved from -3.0 SD before GH therapy to -2.35 SD at presentation. Patients had different forms of immune dysregulation. All patients except for one had either cellular immunodeficiency (3 patients) or combined immunodeficiency (1 patient). Whole exome sequencing was performed and revealed four ACP5 variants c.629C > T (p.Ser210Phe), c.526C > T (p.Arg176Ter), c.742dupC (p.Gln248ProfsTer3) and c.775G > A (p.Gly259Arg). Of them, three variants were not described before. Our study reinforces the striking phenotypic variability associated with SPENCD and expands the mutational spectrum of this rare disorder. Further, it documents the positive response to growth hormone therapy in the studied patient.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autoimmune Diseases
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Mol Genet Genomics
Journal subject:
BIOLOGIA MOLECULAR
/
GENETICA
Year:
2023
Type:
Article
Affiliation country:
Egypt