Analysis of a child with autosomal dominant mental retardation type 40 due to variant of CHAMP1 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic features of a child with autosomal dominant mental retardation type 40 (MRD40) due to variant of the CHAMP1 gene.@*METHODS@#Clinical characteristics of the child were analyzed. Genetic testing was carried out by low-depth high-throughput and whole genome copy number variant sequencing (CNV-seq) and whole exome sequencing (WES). A literature review was also carried out for the clinical phenotype and genetic characteristics of patients with MRD40 due to CHAMP1 gene variants.@*RESULTS@#The child, a 11-month-old girl, has presented with intellectual and motor developmental delay. CNV-seq revealed no definite pathogenic variants. WES has detected the presence of a heterozygous c.1908C>G (p.Y636*) variant in the CHAMP1 gene, which was carried by neither parent and predicted to be pathogenic. Literature review has identified 33 additional children from 12 previous reports. All children had presented with developmental delay and mental retardation, and most had dystonia (94.1%), delayed speech and/or walking (85.2%, 82.4%) and ocular abnormalities (79.4%). In total 26 variants of the CHAMP1 gene were detected, with all nonsense variants being of loss-of-function type, located in exon 3, and de novo in origin.@*CONCLUSION@#The heterozygous c.1908C>G (p.Y636*) variant of the CHAMP1 gene probably underlay the WRD40 in this child. Genetic testing should be considered for children featuring global developmental delay, mental retardation, hypertonia and facial dysmorphism.

Novel compound heterozygous SCN9A variations causing congenital insensitivity to pain in a patient / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child featuring congenital insensitivity to pain (CIP).@*METHODS@#Targeted capture and next generation sequencing (NGS) was carried out for the proband. Suspected pathogenic variants were confirmed by Sanger sequencing of the proband and his parents.@*RESULTS@#The proband was found to harbor compound heterozygous variants of SCN9A gene, namely c.1598delA (p.N533Ifs*31) and c.295_296delCGinsAT (p.R99I), which were respectively inherited from his father and mother. Both variants were predicted to be pathogenic, and neither was reported previously.@*CONCLUSION@#The compound heterozygous variants of the SCN9A gene probably underlay the CIP in this child. Above finding has enabled genetic counseling for this family.

Prenatal diagnosis and genetic counselling for a pedigree carrying a large fragment deletion of 13q / 中华医学遗传学杂志

OBJECTIVE@#To carry out prenatal diagnosis for a fetus with normal ultrasonographic finding at 20 weeks' gestation but a copy number variant(CNV) of 13q indicated by non-invasive prenatal test (NIPT).@*METHODS@#Karyotyping analysis and chromosomal CNV assay were carried out on the amniotic fluid sample. Parental peripheral blood sample was collected for chromosomal analysis. Detailed fetal ultrasound scan was carried out to rule out structural abnormalities of the fetus.@*RESULTS@#The fetus was detected with a heterozygous 10.14 Mb deletion at 13q21.1q21.32, which has originated from the phenotypically normal mother. No apparent karyotypic abnormality was detected in the fetus and its parents. No ultrasonic abnormality was found in the fetus.@*CONCLUSION@#Both the fetus and its mother have carried a heterozygous 10.14 Mb deletion at 13q21.1q21.32 and presented normal phenotypes.Combined with literature review, the segmental deletion was judged to be a benign variant.

Analysis of LRP5 gene variants in a Chinese pedigree affected with Osteoporosis-pseudoglioma syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree with two individuals suffering from congenital blindness.@*METHODS@#Clinical data and peripheral blood samples of the pedigree were collected. Whole exome sequencing was carried out. Suspected variants were verified by Sanger sequencing. Pathogenicity of candidate variants was validated through searching of PubMed and related databases, and analyzed with bioinformatics software.@*RESULTS@#Both patients had congenital blindness and a history of multiple fractures. Other features have included microphthalmia and cornea opacity. One patient had normal intelligence, whilst the other had a language deficit. Both patients were found to harbor compound heterozygous variants of the LRP5 gene, namely c.1007_1015delGTAAGGCAG (p.C336X), c.4400G>A (p.R1467Q) and c.4600C>T (p.R1534X). The first one was derived from their mother, whilst the latter two were derived from their father. None of the three variants was detected in their elder sister.@*CONCLUSION@#The compound heterozygous variants of c.1007_1015delGTAAGGCAG (p.C336X) and c.4600C>T (p.R1534X) of the LRP5 gene probably underlay the pathogenesis of the Osteoporosis-pseudoglioma syndrome in this pedigree. The clinical significance of the c.4400G>A (p.R1467Q) variant has remained uncertain. Above finding has enriched the mutational spectrum of Osteoporosis-pseudoglioma syndrome.

DYNC2H1 gene mutation analysis and prenatal diagnosis in two pedigrees affected with short rib-polydactyly syndrome type Ⅲ / 中华围产医学杂志

Objective:To investigate the molecular genetic etiology of two fetuses with short rib-polydactyly syndrome type Ⅲ (SRPS Ⅲ).Methods:Next-generation sequencing (NGS) was used to detect 226 known genes related to inherited skeletal dysplasia in two fetuses with SRPS Ⅲ diagnosed in the First Affiliated Hospital of Zhengzhou University in August 2015 and June 2020. Suspect pathological variants were verified in the pedigree members using Sanger sequencing. The prenatal genetic diagnosis of the high-risk fetus in pedigree one was conducted to identify the confirmed pathogenic variation.Results:The homozygous mutation of DYNC2H1 gene c.5881A>G(p.Lys1961Glu) was identified in the proband in pedigree one, and the parents were the carriers. The proband in pedigree two carried compound heterozygous mutations in the DYNC2H1 gene with c.10606C>T(p.Arg3536*) inherited from the father and c.8954T>G(p.Val2985Gly) from the mother. Autosomal recessive inheritance was confirmed in both pedigrees. Mutations of c.5881A>G(p.Lys1961Glu) and c.8954T>G(p.Val2985Gly) in the DYNC2H1 gene were likely pathogenic variants and had not been reported before. The prenatal diagnosis did not identify the DYNC2H1 gene c.5881A>G(p.Lys1961Glu) mutation in the fetus (Ⅱ-7) in pedigree one, which was confirmed by the umbilical cord blood sample after birth. Conclusion:DYNC2H1 gene mutation underlies the fetal skeletal dysplasia in the two pedigrees.

Prenatal cytogenetic and molecular genetic analysis of a fetus with confined placenta mosaicism for trisomy 16 / 中华医学遗传学杂志

OBJECTIVE@#To review the clinical data of a fetus with false positive result of non-invasive prenatal testing (NIPT) due to confined placental mosaicism (CPM).@*METHODS@#Amniotic fluid sample was taken from a pregnant women with high risk for chromosome 16 aneuploidy for karyotyping analysis, single nucleotide polymorphism array (SNP array) and interphase fluorescence in situ hybridization (FISH). Genetic testing was also conducted on the fetal and maternal surface of the placenta, root of umbilical cord and fetal skin tissue after induced abortion.@*RESULTS@#Cytogenetic analysis of the amniotic fluid sample yielded a normal karyotype. SNP array revealed mosaicism (20%) of trisomy 16 in the fetus. FISH confirmed the presence of mosaicism (25%) for trisomy 16. After induced labor, all sampled sites of placenta were confirmed to contain trisomy 16 by SNP array, while the analysis of fetal skin tissue yielded a negative result.@*CONCLUSION@#CPM is an important factor for false positive NIPT result. Prenatal identification of CPM and strengthened pregnancy management are important to reduce adverse pregnancy outcomes.

Genetic analysis results and ultrasonographic markers in 41 fetuses with short femurs / 中华围产医学杂志

Objective:To analyze the genetic test results and ultrasonographic markers of 41 fetuses with short femurs and their relationship.Methods:This study retrospectively analyzed 41 fetuses who were diagnosed with short femurs by ultrasound during 19-37 gestational weeks and underwent prenatal genetic examination at the First Affiliated Hospital of Zhengzhou University from January 2018 to June 2019. According to the results of genetic examination, these cases were divided into three groups after excluding three cases of variants of unknown significance: genetically normal group, chromosome variation (including chromosomal aneuploidy and pathogenic or likely pathogenic copy number variations) group, and gene mutation (including pathogenic or likely pathogenic gene mutations) group. According to the head circumference (HC), abdominal circumference (AC) and femur length (FL), Z FL, FL/HC, FL/AC, ΔZ H-F and ΔZ H+A-2F for each fetus were calculated. One-way ANOVA and LSD- t test were used for statistical analysis. Results:(1) Among the 41 fetuses with short femurs, there were 28 in the genetically normal group, five in the chromosome variation group, three with chromosome variations of unknown significance and five in the gene mutation group. (2) In the genetically normal, chromosome variation and gene mutation groups, Z FL values were -2.78±0.77, -4.36±0.69 and -4.69±0.70; FL/HC ratios were 0.178±0.011, 0.170±0.010 and 0.131±0.022; FL/AC ratios were 0.197±0.013, 0.186±0.011 and 0.151±0.017; ΔZ H-F values were 2.49±1.09, 3.53±1.28 and 8.17±1.30; ΔZ H+A-2F values were 4.44±2.00, 6.78±2.20 and 14.28±1.26, respectively. The differences in Z FL values between the genetically normal group and the chromosome variation group as well as the gene mutation group were statistically significant (both P<0.05); so were the differences in FL/HC, FL/AC and ΔZ H-F values between the gene mutation group and the genetically normal group as well as the chromosome variation group (all P<0.05) and in any pairwise comparison of ΔZ H+A-2F among the three groups (all P<0.05). Conclusions:The genetic etiology of fetal short femurs is mainly related to chromosomal variations (including chromosomal aneuploidy and pathogenic or likely pathogenic copy number variations) and gene mutation. In fetuses with chromosome variation and gene mutation, the degree of the femoral development delay relative to the development of HC and AC is worse than that in the normal genetic results group.

Genetic testing and prenatal diagnosis for a Chinese pedigree affected with Meckel-Gruber syndrome / 中华医学遗传学杂志

OBJECTIVE@#To carry out genetic testing and prenatal diagnosis for a Chinese couple whom had conceived two fetuses featuring multiple malformations including polycystic kidney, polydactyly and encephalocele.@*METHODS@#Following elective abortion, the fetus from the second pregnancy was subjected to whole exome sequencing. Suspected pathogenic variants were verified by Sanger sequencing of the fetus and its parents.@*RESULTS@#The fetus was found to harbor compound heterozygous variants of the CEP290 gene, namely c.2743G>T (p.E915X) and c.2587-2A>T, which were respectively inherited from its father and mother. The same variants were not detected among 100 healthy controls nor reported previously. Bioinformatic analysis suggested both variants to be deleterious. The fetus was diagnosed with Meckel-Gruber syndrome. Prenatal diagnosis for the couple during their next pregnancy suggested that the fetus did not carry the above pathogenic variants.@*CONCLUSION@#The compound heterozygous variants of the CEP290 gene probably underlay the pathogenesis of Meckel-Gruber syndrome in the second fetus. Above finding has provided a basis for genetic counseling and prenatal diagnosis for the couple, and also enriched the mutational spectrum of the CEP290 gene.

Diagnosis of a patient with adjacent gene deletion syndrome with DMD complete deletion type of Duchenne muscular dystrophy / 中华医学遗传学杂志

OBJECTIVE@#To identify the etiology of a patient with severe symptoms of DMD and to trace its pathogenic gene, so as to provide a basis for genetic counseling and clinical intervention.@*METHODS@#Multiple ligation-dependent probe amplification (MLPA) technique was used to analyze exon deletion/repetitive variant of DMD gene, and further analysis was performed by chromosome G-banding, fluorescence in situ hybridization (FISH) and SNP array analysis.@*RESULTS@#The MLPA results of the proband showed that the exon 1-79 of DMD gene were deleted, the G-banding karyotype of blood sample was 46, XY, and the deletion of the short arm of X chromosome was found by FISH. SNP array results showed that 5.8Mb (29 628 158-35 434 714) deletion occurred in the Xp21.2p21.1 region of X chromosome, and the patient was diagnosed as the contiguous deletion syndrome involving the genes of IL1RAPL, MAGEB1-4, ROB, CXorf2, GM, AP3K7IP, FTHL1, DMD, FAM47A, TMEM47, and FAM47B.@*CONCLUSION@#The exact pathogenic site of this family is the deletion of 5.8 Mb (29 628 158-35 434 714) in the Xp21.2p21.1 region of X chromosome, which can be used for prenatal diagnosis. High resolution SNP array technique plays an important role in detecting potential chromosome abnormalities in patients.

Analysis of COL1A1 gene variants in five Chinese pedigrees affected with osteogenesis imperfecta / 中华医学遗传学杂志

OBJECTIVE@#To detect potential variants of COL1A1 gene in five Chinese pedigrees affected with osteogenesis imperfecta (OI) and provide prenatal diagnosis for a fetus at 11th gestational week.@*METHODS@#The coding regions and exon/intron boundaries of 225 genes associated with bone diseases were subjected to targeted capture and next generation sequencing (NGS). Suspected mutations were verified with Sanger sequencing in the probands, unaffected relatives and 100 unrelated healthy controls. Prenatal diagnosis for a high-risk fetus was carried out by Sanger sequencing.@*RESULTS@#The probands of the pedigrees 1-5 have respectively carried c.3226G>A (p.Gly1076Ser), c.579delT (p.Gly194Valfs*71), c.2911-2912insAG (p.Gly971Glufs*138), c.3037G>A (p.Gly1013Arg) and c.642+5G>A variants of the COL1A1 gene. For pedigree 1, the same variant was not found in the fetus. c.3037G>A (p.Gly1013Arg) and c.2911-2912insAG (p.Gly971Glufs*138) were not reported previously.@*CONCLUSION@#Mutations of the COL1A1 gene probably underlie the OI in the five pedigrees. Combined NGS and Sanger sequencing can provide an effective and accurate method for the genetic and prenatal diagnosis of OI.

Clinical phenotype and genetic analysis of three pedigrees with 17q12 microdeletion syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of three pedigrees with a gestational history of fetal renal anomalies.@*METHODS@#Peripheral venous blood or skin samples were derived from the probands of the three pedigrees. Copy number variation sequencing (CNV-seq) was applied to detect alterations of genome CNVs.@*RESULTS@#The patient from pedigree 1 and the fetuses from pedigrees 2 and 3 all carried a heterozygous 17q12 deletion, with the size ranging from 1.4 Mb to 1.48 Mb encompassing the HNF1B gene.@*CONCLUSION@#The diagnosis of 17q12 microdeletion may be difficult during fetal period for its variable phenotypes. Alterations of chromosomal copy numbers need to be excluded in such patients.

SGCA gene mutation analysis and prenatal diagnosis of two pedigrees with limb-girdle muscular dystrophy type 2D / 中华围产医学杂志

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.

Ultrasonographic manifestation and genetic analysis of a fetus with nephronophthisis type 2 / 中华医学遗传学杂志

OBJECTIVE@#To carry out genetic analysis for a family with a fetus manifesting bilateral polycystic renal dysplasia and oligohydramnios at 16 gestational week and a previous history for fetal renal anomaly.@*METHODS@#Ultrasound scan was carried out to detect the morphological changes. Following genetic counselling, the parents had decided to terminate the pregnancy. Fetal kidneys were subjected to histological examination. Target capture and next generation sequencing (NGS) was applied to the abortus to detect potential variants. The results were verified by Sanger sequencing.@*RESULTS@#Histological examination of fetal kidneys revealed cystic changes without cortex, medulla or normal renal structure. NGS has identified a heterozygous c.100+1G>A variant and deletion of exon 3 of the INVS gene, which were respectively inherited from the mother and father.@*CONCLUSION@#Through NGS and Sanger sequencing, the fetus was diagnosed with type II nephronophthisis (NPHP2). Above result can provide guidance for further pregnancy and enforce understanding of clinical features and genetic etiologies for NPHP.

Genetic analysis of five pedigrees affected with multiple osteochondromas / 中华医学遗传学杂志

OBJECTIVE@#To detect variants of EXT1 and EXT2 genes among five pedigrees affected with multiple osteochondromas and provide prenatal diagnosis for the families based on the results.@*METHODS@#The EXT1 and EXT2 genes of the probands were analyzed by targeted next generation sequencing (NGS). Suspected pathological variants were validated by Sanger sequencing in the probands, their family members and 200 unrelated healthy controls. Multiple ligation-dependent probe amplification (MLPA) was used to confirm the presence of gross deletions. Prenatal diagnosis was provided for 2 couples carrying pathogenic or likely pathogenic variants.@*RESULTS@#Five variants were detected in the pedigrees, which included EXT1 exon 2-3 deletion, c.1468dupC (p.Leu490ProfsX31), c.2084delC (p.Pro695LeufsX11), and EXT2 c.187delT (p.Phe63SerfsX29) and c.1362T>G (p.Tyr454X). Among these, EXT1 exon 2-3 deletion, c.2084delC (p.Pro695LeufsX11) and EXT2 c.187delT (p.Phe63SerfsX29) were unreported previously. The three novel variants were not found among unaffected members of the pedigree and the 200 healthy controls. Upon prenatal diagnosis, the two fetuses were found to carry the same variants of the the probands.@*CONCLUSION@#Pathological variants of the EXT1 and EXT2 genes probably underlie the multiple osteochondromas among the 5 pedigrees. Prenatal diagnosis based on the results can effectively reduce the birth of further offspring affected with the disease.

Phenotype and genetic analysis of three patients with PKHD1 associated autosomal recessive polycystic kidney disease at childhood, teenage and advanced age / 中华医学遗传学杂志

OBJECTIVE@#The phenotype and genetics of three patients with autosomal recessive polycystic kidney disease (ARPKD) at childhood, teenage and advanced age were analyzed.@*METHODS@#Next generation sequencing (NGS) was applied to all the probands. PCR and Sanger sequencing were used to verify the suspicious gene variants screened by NGS in the probands and their family members, and one of the family got prenatal diagnosis.@*RESULTS@#Through NGS, PCR and Sanger sequencing, the 5-yr proband in pedigree 1 was shown to carry compound heterozygous variants of c.5935G>A(p.G1979R) and c.5428G>T(p.E1810X) of PKHD1, originated from his parents; In pedigree 2, the 17-ys proband was detected with c.5512T>C(p.Y1838H) and c.5935G>A(p.G1979R) variants of PKHD1 orginated from her parents, and her mother also got prenatal diagnosis during the second trimester; In pedigree 3, the 70-ys female proband was found with variants c.11314C>T (p.R3772X) and c.3860T>G (p.V1287G) of PKHD1.@*CONCLUSION@#The three pedigrees were diagnosed as ARPKD caused by PKHD1 variants. Five types of variants were detected, c.5935G>A and c.11314C>T were the known pathogenic variants, while c.5512T>C, c.5428G>T and c.3860T>G were not reported previously. Considering the complexity of the genetics and phenotypes of the cystic renal diseases, genetic diagnosis is crucial to give accurate etiological diagnosis, which may benefit the clinic management.

Prenatal diagnosis for two families affected with cleidocranial dysplasia due to novel RUNX2 variants / 中华医学遗传学杂志

OBJECTIVE@#To analyze variants of RUNX2 gene in two pedigrees affected with cleidocranial dysplasia and provide prenatal diagnosis for them.@*METHODS@#For the two probands, the coding sequences of the RUNX2 gene were analyzed with PCR and bidirectional Sanger sequencing. To verify the results, peripheral blood samples were collected from their parents and 100 healthy controls. For family 1, umbilical cord blood was also collected for prenatal genetic diagnosis.@*RESULTS@#In family 1, the proband and the fetus both carried a heterozygous c.578G>C (p.Arg193Pro) mutation. For family 2, the proband was found to carry a heterozygous c.909C>A (p.Tyr303X) mutation. The same mutations were not found among their parents and 100 healthy controls. Neither mutation was reported previously.@*CONCLUSION@#Variants of the RUNX2 gene probably underlie the cleidocranial dysplasia in both pedigrees. The results enabled prenatal diagnosis for the affected family.

Two cases of rare diseases with abnormalities of X chromosome / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genetic diagnosis of two cases with rare diseases and X chromosome abnormalities.@*METHODS@#Multiple ligation-dependent probe amplification (MLPA) and karyotype analysis were carried out on an 8-year-old girl who was diagnosed with Duchenne muscular dystrophy. Karyotype analysis and PCR assay for SRY and AZF genes were carried out for a-2-month-old male infant with short penis.@*RESULTS@#The girl, who featured short stature and cubitus valgus, was diagnosed as Turner syndrome with a karyotype of 46,X,i(Xq). The male infant was detected with a karyotype of 45,X, with presence of SRY gene but absence of AZF gene.@*CONCLUSION@#Both cases may be associated with abnormalities of X chromosome. Genetic testing can facilitate early diagnosis and clinical intervention for such patients.

Genetic analysis of a family with recurrent hydrops fetalis and dilated cardiomyopathy / 中华医学遗传学杂志

Objective@#To carry out genetic testing for a family with two pregnancies affected with hydrops fetalis and dilated cardiomyopathy (DCM) of the fetus.@*Methods@#DNA was extracted from fetal tissue as well as peripheral blood samples from the couple. Single nucleotide polymorphism array (SNP array) and next-generation sequencing (NGS) were carried out to screen potential mutation. Suspected mutation was validated with PCR and Sanger sequencing.@*Results@#The manifestation of fetal echocardiography was consistent with DCM. No obvious abnormality was found by SNP array analysis. A hemizygous c. 481G>A (p.G161R) mutation of the TAZ gene was detected in the male fetus by NGS and confirmed by Sanger sequencing. The mutation was inherited from his mother.@*Conclusion@#Barth syndrome due to the c. 481G>A mutation of the TAZ gene probably underlies the recurrent hydrops fetalis and fetal DCM in this family.

Genetic analysis of a family with recurrent hydrops fetalis and dilated cardiomyopathy / 中华医学遗传学杂志

OBJECTIVE@#To carry out genetic testing for a family with two pregnancies affected with hydrops fetalis and dilated cardiomyopathy (DCM) of the fetus.@*METHODS@#DNA was extracted from fetal tissue as well as peripheral blood samples from the couple. Single nucleotide polymorphism array (SNP array) and next-generation sequencing (NGS) were carried out to screen potential mutation. Suspected mutation was validated with PCR and Sanger sequencing.@*RESULTS@#The manifestation of fetal echocardiography was consistent with DCM. No obvious abnormality was found by SNP array analysis. A hemizygous c.481G>A (p.G161R) mutation of the TAZ gene was detected in the male fetus by NGS and confirmed by Sanger sequencing. The mutation was inherited from his mother.@*CONCLUSION@#Barth syndrome due to the c.481G>A mutation of the TAZ gene probably underlies the recurrent hydrops fetalis and fetal DCM in this family.

Prenatal diagnosis for two families affected with cleidocranial dysplasia due to novel RUNX2 variants / 中华医学遗传学杂志

Objective@#To analyze variants of RUNX2 gene in two pedigrees affected with cleidocranial dysplasia and provide prenatal diagnosis for them.@*Methods@#For the two probands, the coding sequences of the RUNX2 gene were analyzed with PCR and bidirectional Sanger sequencing. To verify the results, peripheral blood samples were collected from their parents and 100 healthy controls. For family 1, umbilical cord blood was also collected for prenatal genetic diagnosis.@*Results@#In family 1, the proband and the fetus both carried a heterozygous c. 578G>C (p.Arg193Pro) mutation. For family 2, the proband was found to carry a heterozygous c. 909C>A (p.Tyr303X) mutation. The same mutations were not found among their parents and 100 healthy controls. Neither mutation was reported previously.@*Conclusion@#Variants of the RUNX2 gene probably underlie the cleidocranial dysplasia in both pedigrees. The results enabled prenatal diagnosis for the affected family.