Severe Congenital Neutropenia Type 4: A Rare Disease Harboring a G6pc3 Gene Pathogenic Variant Particular to the Mexican Population
Document title: Severe Congenital Neutropenia Type 4: A Rare Disease Harboring a G6pc3 Gene Pathogenic Variant Particular to the Mexican Population
Journal: Revista de investigación clínica
Database: PERIÓDICA
System number: 000452917
ISSN: 0034-8376
Authors: 1
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Institutions: 1Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Departamento de Genética, Ciudad de México. México
Year:
Season: Nov-Dic
Volumen: 74
Number: 6
Pages: 328-339
Country: México
Language: Inglés
Document type: Artículo
Approach: Experimental, aplicado
English abstract Background: Severe congenital neutropenia type 4 (SCN4) is a rare autosomal recessive granulopoiesis disorder caused by G6PC3 gene pathogenic variants. The estimated prevalence is 1/10,000,000 people. Over 90% of patients present a syndromic form with variable multisystemic involvement, including congenital heart defects, increased visibility of superficial veins (IVSV), inflammatory bowel disease, and congenital urogenital defects as prominent symptoms. Objectives: The objective of the study was to study non-hematological phenotypic findings that suggest a clinical diagnosis of SCN4. Methods: We examined medical records of patients diagnosed with neutropenia from January 2000 to December 2020, selecting cases with non-hematologic manifestations for phenotypic description and G6PC3 gene sequencing. Results: We found 11 cases with non-hematologic features: congenital heart defects in 8, IVSV in 6, inflammatory bowel disease in 4, urogenital defects in 4, and similar facial appearance. In addition, Sanger sequencing confirmed 3 homozygous cases for the c.210delC variant, a compound heterozygous harboring this variant, and a c.199_218+1 deletion. Conclusions: Our findings of the c.210delC variant in very close geographical settings, to date, have only been reported among Mexicans, and a mutual uncommon surname in two families strongly supports a founder effect for the variant in the studied population. Furthermore, the described non-hematologic symptoms in patients with severe primary neutropenia should be explored, confirming SCN4 by investigating G6PC3 gene mutations
Disciplines: Medicina
Keyword: Genética,
Inmunología,
Neutropenia,
Neutropenia congénita severa,
Mutaciones génicas
Keyword: Genetics,
Immunology,
Neutropenia,
Severe congenital neutropenia,
Gene mutations
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