The spectrum of novel ABCB11 gene variations in children with progressive familial intrahepatic cholestasis type 2 in Pakistani cohorts.
Sci Rep
; 14(1): 18876, 2024 08 14.
Article
en En
| MEDLINE
| ID: mdl-39143102
ABSTRACT
Progressive familial intrahepatic cholestasis (PFIC) is a rare childhood manifested disease associated with impaired bile secretion with severe pruritus yellow stool, and sometimes hepatosplenomegaly. PFIC is caused by mutations in ATP8B1, ABCB11, ABCB4, TJP2, NR1H4, SLC51A, USP53, KIF12, ZFYVE19, and MYO5B genes depending on its type. ABCB11 mutations lead to PFIC2 that encodes the bile salt export pump (BSEP). Different mutations of ABCB11 have been reported in different population groups but no data available in Pakistani population being a consanguineous one. We sequenced coding exons of the ABCB11 gene along with its flanking regions in 66 unrelated Pakistani children along with parents with PFIC2 phenotype. We identified 20 variations of ABCB11 12 in homozygous form, one compound heterozygous, and seven heterozygous. These variants include 11 missenses, two frameshifts, two nonsense mutations, and five splicing variants. Seven variants are novel candidate variants and are not detected in any of the 120 chromosomes from normal ethnically matched individuals. Insilico analysis revealed that four homozygous missense variations have high pathogenic scores. Minigene analysis of splicing variants showed exon skipping and the addition of exon. This data is a useful addition to the disease variants genomic database and would be used in the future to build a diagnostic algorithm.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Colestasis Intrahepática
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Miembro 11 de la Subfamilia B de Transportador de Casetes de Unión al ATP
Límite:
Child
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Child, preschool
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Female
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Humans
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Infant
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Male
País/Región como asunto:
Asia
Idioma:
En
Revista:
Sci Rep
Año:
2024
Tipo del documento:
Article
País de afiliación:
Canadá