Mutations in DMD genes can lead to muscular dystrophy (DMD or BMD). If the deletion or duplication mutations in DMD gene destroys the reading frame and result in the anti-myatrophin protein content less than 3% or can't produce myoatrophin, patients show DMD. If deletion or duplication mutations keep the reading frame intact or less destoryed , it leads to the anti-myojiatrophy protein keeping part of the function, patients show BMD. But there are also a few patients who DMD gene deletion or duplication did not alter the reading frame , it still show DMD. [8]
The main DMD gene mutation type of is partial deletion or repetition of 79 gene exons, nearly account for 60%~70% of all mutation types. The rest are point mutations, minor insertion or deletion mutations|. Despite many studies on gene therapy in DMD, such as exon hopping, readout of nonsense stop codon or injection of vectors with full DMD gene, gene therapy still faces great challenges and dilemmas[9]. There is still no effective treatment for DMD/BMD patients until now [10,11], early diagnosis and early treatment can prolong the survival age and improve the quality of life of DMD patients, but can not be cured. DMD patients with no family history of hereditary diseases can not usually be found before birth [12-16]. A majority of DMD patients develop clinical symptoms around age 3. But the results of serum creatine kinase level, neuroelectrical trophysiological examination and DMD gene detection were clearly diagnosed until 5 years old, so genetic counseling and screening for DMD genes prior to or in early pregnancy are particularly important, prenatal diagnosis is an important approach to prevent the birth of the patient with a family history of DMD/BMD or with no history.
High-resolution genomic CMA and high-throughput next generation sequencing CNV were used in prenatal diagnosis not only detect chromosomal microdeletion and microduplication syndrome, but also helped to detect single gene disease caused by gene deletion or duplication, can improve the diagnosis rate of disease. In this study, the pregnancy of all male fetuses were terminated. Two female fetuses were born: Case6 is normal; but Case 3 showed upward bent legs and heavy hair, WES did not find problems. One female fetus (Case 5) was aborted.,( data of 7 patients showed in Tab 1).We compared the DMD gene mutations between fetus and mother, found some mutations inherited from mother(Fig 1) and some didn’t(Fig 2), it also reveals the importance of prenatal diagnosis because the mother is carrier or healthy woman, and with no family history of DMD. So it is beneficial to the correct evaluation of fetal prognosis in prenatal clinical consultation, and provide a more comprehensive advice to decide if the pregnancy should continue or be terminated to prevent the birth of children with defects.
Table 1
Clinical and experimental data of the 7 analyzed patients
Case
|
Weeks
|
Gender
|
Medical history
|
Sample
|
Results
|
MLPA
|
Inheritance
|
Follow-up
|
1
|
24+1
|
male
|
Omphalocele
|
amniotic fluid
|
Xp21.1(31691172_31766673)x0 (CMA)
|
E52-53
del
|
Y
|
abortion
|
2
|
30
|
male
|
1.right aortic arch
2.left artery vagal
3.left ventricular bright spot.
|
amniotic fluid
|
Xp21.2(31016983_31351900)x2 (CMA)
|
E61-79
dup
|
Y
|
abortion
|
3
|
32+1
|
female
|
1.NF:6.8mm
2.Down risk:1:413
|
amniotic fluid
|
Xp21.2(31182699_31474949)x3 (CMA)
|
E58-74
dup
|
Y
|
born with problems
|
4
|
31+3
|
male
|
sacrococcygeal vertebrae dysplasia
|
amniotic fluid
|
Xp21.1(31777925_32152126)x2 (CMA)
|
E45-51
dup
|
Y
|
abortion
|
5
|
24+5
|
female
|
Down risk:1:227
|
amniotic fluid
|
dup(X)(p21.2) chrX:g.30860000_31260000
(CNV-seq)
|
E64-79
dup
|
N
|
abortion
|
6
|
22+6
|
female
|
Sex Chromosome Number Variant (NIPT)
|
amniotic fluid
|
dup(X)(p21.1)chrX:g.32820000_33560000
(CNV-seq)
|
E1-7
dup
|
N
|
born
|
7
|
21+2
|
female
|
1.skin edema
2.scites
3.bilateral foot varus
|
aborted fetus
|
del(X)(p21.1) chrX:g.31760000_32000000
(CNV-seq)
|
E45-51
del
|
Y
|
|