Loss of helicase C-terminal domain of SMARCAL1 protein associated with severe Schimke immuno-osseous dysplasia.
Pathol Res Pract
; 254: 155092, 2024 Feb.
Article
en En
| MEDLINE
| ID: mdl-38218042
ABSTRACT
Schimke immuno-osseous dysplasia (SIOD) is a rare multi-system condition caused by biallelic loss-of-function mutations in the SMARCAL1 gene. This disorder is characterized by disproportionate growth failure, T-cell deficiency, and renal dysfunction. Pathogenic variants in the SMARCAL1 gene have been reported in only approximately half of SIOD-affected individuals. Among these alterations, nonsense and frameshift mutations generally lead to a severe phenotype with early onset. In this study, we identified novel mutations in an Iranian patient with SIOD. A 4-year-old girl with developmental delay and facial dysmorphism was referred to our center for molecular diagnosis. We applied whole-exome and Sanger sequencing for co-segregation analysis. Subsequently, bioinformatic analysis was performed to assess the pathogenic effects of the variants and their post-transcriptional effects. We discovered two novel mutations (c.2281delT and c.2283delA) in exon 15 of the SMARCAL1 gene, resulting in a truncated protein with a loss of 193 amino acids (p.S761Rfs*1). Variant effect predictors indicated that these variants are pathogenic, and multi-sequence alignments revealed high conservation of this region among different species. Given that our patient exhibited severe a phenotype and passed away soon after receiving a definitive molecular diagnosis, we propose that the loss of the helicase C-terminal domain in the deleted part of SMARCAL1 may lead to the severe form of SIOD. Besides, the combination of growth retardation and bone abnormalities also plays a crucial role in the early diagnosis of the disease.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Osteocondrodisplasias
/
Arteriosclerosis
/
Embolia Pulmonar
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Enfermedades de Inmunodeficiencia Primaria
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Síndromes de Inmunodeficiencia
/
Síndrome Nefrótico
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Screening_studies
Límite:
Child, preschool
/
Female
/
Humans
País/Región como asunto:
Asia
Idioma:
En
Revista:
Pathol Res Pract
Año:
2024
Tipo del documento:
Article
País de afiliación:
Irán