SGCA gene mutation analysis and prenatal diagnosis of two pedigrees with limb-girdle muscular dystrophy type 2D
10.3760/cma.j.cn113903-20190112-00010
- VernacularTitle:两个肢带型肌营养不良2D型家系 SGCA基因遗传分析和产前诊断
- Author:
Yanjie XIA
1
;
Zhihui JIAO
;
Qinghua WU
;
Xiangdong KONG
Author Information
1. 郑州大学第一附属医院遗传与产前诊断中心 450052
- From:
Chinese Journal of Perinatal Medicine
2020;23(3):208-213
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the variations of SGCA gene in two Chinese pedigrees of Han nationality with limb-girdle muscular dystrophy type 2D (LGMD2D) and provide prenatal diagnosis and genetic counseling for subsequent pregnancies within the pedigrees. Methods:This study involved two unrelated patients who were the probands of their pedigrees diagnosed with LGMD2D in the First Affiliated Hospital of Zhengzhou University from June 2017 to January 2018. Genomic DNA was extracted from peripheral blood samples of the probands and their parents. Coding sequences and flanking sequences of 21 LGMD-related genes from the probands were captured and subjected to high-throughput sequencing. Suspected mutations in their parents were detected and validated by Sanger sequencing and/or fluorescence quantitative polymerase chain reaction (PCR). Prenatal genetic diagnosis for high-risk fetuses in the two pedigrees was performed after the causative factors being identified.Results:(1) The proband of pedigree 1 carried compound heterozygous point mutations in SGCA gene with c.218C>G(p.P73R) and c.101G>A(p.R34H) inherited from his father and mother, respectively. Prenatal diagnosis indicated that the second fetus of the family carried the same mutations as the proband, and the family chose to terminate the gestation. (2) The proband of pedigree 2 inherited the compound heterozygous mutations of c.218C>T (p.P73L) and heterozygous deletion of exons 7 and 8 in SGCA gene from his parents. Their second fetus did not carry any of the above mutations and was delivered at full term. Serum creatinase level and physical, motor and mental development of the child were all within the normal range during a two-year follow-up after birth. Conclusions:The heterozygous mutations in SGCA gene are the cause of LGMD2D in the two pedigrees, and c.218C>G(p.P73R) and c.218C>T(p.P73L) are novel mutations. Genetic and prenatal diagnosis based on high-throughput targeted next-generation sequencing can rapidly and accurately detect the mutations responsible for LGMD2D.
