Your browser doesn't support javascript.
loading
Identification of novel compound heterozygous variants of the ALMS1 gene in a child with Alström syndrome by whole genome sequencing.
Xu, Haikun; Wang, Ziju; Sa, Sha; Yang, Ying; Zhang, Xiaofei; Li, Dejun.
Afiliación
  • Xu H; Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun 130033, P.R. China.
  • Wang Z; Department of Pediatrics, China-Japan Union Hospital of Jilin University, Changchun 130033, P.R. China.
  • Sa S; Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun 130033, P.R. China.
  • Yang Y; Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun 130033, P.R. China.
  • Zhang X; Department of Pediatrics, China-Japan Union Hospital of Jilin University, Changchun 130033, P.R. China. Electronic address: xiaofei@jlu.edu.cn.
  • Li D; Center for Reproductive Medicine and Prenatal Diagnosis, The First Hospital of Jilin University, Changchun 130021, P.R. China. Electronic address: lidejun@jlu.edu.cn.
Gene ; 929: 148827, 2024 Dec 15.
Article en En | MEDLINE | ID: mdl-39122231
ABSTRACT

BACKGROUND:

Alström syndrome (ALMS), a rare recessively inherited ciliopathy caused by mutations in ALMS1, is characterized by retinal dystrophy, childhood obesity, sensorineural hearing loss, and type 2 diabetes mellitus. The majority of pathogenic variants in ALMS1 are nonsense and frameshift mutations, which would lead to premature protein truncation, whereas copy number variants are seldom reported.

METHODS:

Herein, we present a 10-year-old Chinese girl with ALMS. The potential causative genetic variant was confirmed through whole genome sequencing, quantitative real-time PCR analysis, and Sanger sequencing. Additionally, breakpoint analysis was performed to determine the exact breakpoint site of the large deletion and elucidate its probable formation mechanism.

RESULTS:

The patient had a cor triatriatum sinister (CTS) structure. Genetic analysis identified novel compound heterozygous variants in the patient, consisting of a frameshift variant c.4414_4415delGT (p.V1472Nfs*26) in ALMS1 and a novel large deletion at chr273,612,355-73,626,339, which encompasses exon 1 of the ALMS1 gene. Moreover, breakpoint analysis revealed that the large deletion probably formed through the microhomology-mediated end joining (MMEJ) mechanism due to the 6-bp microhomologies (TCCTTC) observed at both ends of the breakpoints.

CONCLUSIONS:

In this study, novel compound heterozygous variants in the ALMS1 gene were identified in an ALMS patient with a CTS structure. The molecular confirmation of these variants expands the mutational spectrum of ALMS1, while the manifestation of ALMS in the patient provides additional clinical insights into this syndrome.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mutación del Sistema de Lectura / Proteínas de Ciclo Celular / Síndrome de Alstrom / Secuenciación Completa del Genoma / Heterocigoto Límite: Child / Female / Humans Idioma: En Revista: Gene Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mutación del Sistema de Lectura / Proteínas de Ciclo Celular / Síndrome de Alstrom / Secuenciación Completa del Genoma / Heterocigoto Límite: Child / Female / Humans Idioma: En Revista: Gene Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos