2.Clinical and genetic analysis of a patient with Mowat-Wilson syndrome.
Pingli ZHANG ; Yanqi HOU ; Peiyuan LIAO ; Xiang YUAN ; Na LI ; Qikun HUANG ; Jing YANG
Chinese Journal of Medical Genetics 2021;38(5):465-468
OBJECTIVE:
To summarize the clinical phenotype and genotype of a Chinese child affected with Mowat-Wilson syndrome (MWS).
METHODS:
Clinical data of the patient were collected. The patient was analyzed by whole-exome sequencing (WES) as well as Sanger sequencing.
RESULTS:
The patient was a male infant with recurrent fever and slow growth. He also had characteristic facies, recurrent spasm, and growth retardation. WES revealed that he has carried a heterozygous nonsense c.2609C>G (p.Ser870X) variant of the ZEB2 gene (30% mosaicism). Based on the American College of Medical Genetics and Genomics standards and guidelines, the variant was predicted to be pathogenic (PVS1+PS1+PS2+PM2).
CONCLUSION
The c.2609C>G variant of the ZEB2 gene probably underlay the MWS in this child. The mosaicism of the variant may explain his mild symptoms.
Child
;
Facies
;
Hirschsprung Disease/genetics*
;
Humans
;
Infant
;
Intellectual Disability/genetics*
;
Male
;
Microcephaly/genetics*
;
Mutation
3.Clinical characteristics and genetic analysis of 3 children with Mowat-Wilson syndrome.
Taocheng ZHOU ; Yuchen WANG ; Dong LIANG ; Lulu CHEN ; Fuling YE ; Hongyao CAO ; Guanglei TONG
Chinese Journal of Medical Genetics 2022;39(9):944-948
OBJECTIVE:
To explore the genetic basis of three children with unexplained mental retardation/developmental delay.
METHODS:
Peripheral venous blood samples were collected for routine G-banding karyotyping analysis and chromosomal microarray analysis (CMA). Whole exome sequencing (WES) was also carried out for patient 3.
RESULTS:
The karyotypes of the 3 children were normal. The result of CMA analysis of patient 1 was arr[GRCh37]: 2q22/3(145 128 071-145 159 029)×1, with a 31 kb deletion, which was predicted to be a pathogenic copy number variation. The deletion has involved exons 8 to 10 of the ZEB2 gene. Patient 2 was arr[hg19]:2q22.3 (145 071 457-146 881 759)×1, with a 1.81 Mb deletion involving the ZEB2 and GTDC1 genes. Patient 3 was arr[GRCh37]: 9p23p23(11 698 261-12 106 261)×1, with a 408 kb deletion containing no disease-associated gene. WES has identified a c.2102C>A (p.Ser701*) variant in exon 8 of the ZEB2 gene, which was included in ClinVar database and rated as pathogenic, and verified by Sanger sequencing as a de novo variant.
CONCLUSION
For the substantial clinical and genetic heterogeneity of Mowat-Wilson-syndrome, CMA and WES are helpful to identify the etiology of children with developmental delay/mental retardation of unknown causes, particularly those with peculiar facial features and multiple congenital malformations.
Child
;
DNA Copy Number Variations
;
Facies
;
Glycosyltransferases/genetics*
;
Hirschsprung Disease
;
Humans
;
Intellectual Disability/genetics*
;
Microcephaly/genetics*
4.Genetic analysis of microcephaly-cortical blind syndrome due to compound heterozygous variants of DIAPH1 gene.
Xiaobing LI ; Panjian LAI ; Kaichao CHENG ; Dayan WANG
Chinese Journal of Medical Genetics 2022;39(10):1116-1119
OBJECTIVE:
To explore the genetic etiology of a child with microcephaly-cortical blind syndrome.
METHODS:
Clinical data of the child was collected. The child and her parents were subjected to whole exome sequencing (WES). Candidate variants were validated by Sanger sequencing.
RESULTS:
WES revealed that the child has harbored compound heterozygous variants c.1051C>T and c.609delA of the DIAPH1 gene.
CONCLUSION
The compound heterozygous variation c.1051C>T (p.R351X) and c.609delA (p.E203Efs*19) of the DIAPH1 gene probably underlay the microcephaly-cortical blindness syndrome in this child.
Blindness/genetics*
;
Child
;
Female
;
Formins/genetics*
;
Genetic Testing
;
Humans
;
Microcephaly/genetics*
;
Mutation
;
Pedigree
;
Exome Sequencing
5.Clinical and genetic analysis of a child with Alazami syndrome due to compound heterozygous variants of LARP7 gene.
Lin YUAN ; Peng ZHAO ; Qianqian SHENG ; Weihang MU ; Gang XU ; Jian LIU
Chinese Journal of Medical Genetics 2023;40(7):860-864
OBJECTIVE:
To analyze the clinical phenotype and genetic basis of a child with Alazami syndrome (AS).
METHODS:
A child who presented at Tianjin Children's Hospital on June 13, 2021 was selected as the study subject. The child was subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing.
RESULTS:
WES revealed that the child has harbored two frameshifting variants of the LARP7 gene, namely c.429_430delAG (p.Arg143Serfs*17) and c.1056_1057delCT (p.Leu353Glufs*7), which were verified by Sanger sequencing to be respectively inherited from his father and mother.
CONCLUSION
The compound heterozygous variants of the LARP7 gene probably underlay the pathogenesis in this child.
Female
;
Humans
;
Dwarfism/genetics*
;
Exome Sequencing
;
Intellectual Disability/genetics*
;
Microcephaly
;
Mothers
;
Mutation
;
Male
;
Child
6.Siblings Seckel's syndrome 1 caused by ATR gene variants in a sibpair.
Mingfang QIU ; Ziqin LIU ; Xiaobo CHEN
Chinese Journal of Medical Genetics 2021;38(10):973-976
OBJECTIVE:
Two brothes with Seckel's syndrome 1(SCKL1) were reported and a literature review was carried to provide clinical and genetic information of this rare disease.
METHODS:
Clinical data of the two children were collected, and the peripheral blood was extracted for whole exome sequencing. Literature of the disease were reviewed.
RESULTS:
The two patients were 11 years and 9.5 years old when examined for short stature. They presented with intrauterine growth retardation, intellectual disability, microcephaly, birdhead-like face and coffee au lait spots. The bone age was more than 2 years behind the chronical age and the growth hormone levels were normal. Whole exome sequencing revealed novel compound heterozygous variants c.1A>G (p.M1?) and c.4853-18A>G of ART gene in both children.
CONCLUSION
Children with prenatal onset short stature, developmental delay, microcephaly and special facial featuresshould be considered for the possibility of Seckel's syndrome, whole exome sequencing could help to confirm the clinical diagnosis.
Ataxia Telangiectasia Mutated Proteins/genetics*
;
Child
;
Dwarfism/genetics*
;
Humans
;
Intellectual Disability/genetics*
;
Male
;
Microcephaly/genetics*
;
Siblings
;
Whole Exome Sequencing
7.Available Evidence of Association between Zika Virus and Microcephaly.
Jing WU ; Da-Yong HUANG ; Jun-Tao MA ; Ying-Hua MA ; Yi-Fei HU
Chinese Medical Journal 2016;129(19):2347-2356
OBJECTIVETo clarify the possible association between the Zika virus (ZIKV) and microcephaly and understand where we are in terms of research and the debate on the causation between mild maternal clinical features and severe fetal microcephaly.
DATA SOURCESWe did a comprehensive literature review with the keywords "zika" and/or "microcephaly" from inception to May 27, 2016, with PubMed.
STUDY SELECTIONStudies were included and analyzed if they met all of the following criteria: "probable or confirmed infant microcephaly" and "probable or confirmed ZIKV infection among mothers or infants".
RESULTSWe emphasize the diagnosis of ZIKV infection, including maternal clinical manifestations, maternal and fetal laboratory confirmation, and possible autopsy if need. Other confounders that may lead to microcephaly should be excluded from the study. We presented the results from clinical manifestations of ZIKV infection, testing methods evolving but the mechanism of microcephaly uncertain, flexible definition challenging the diagnosis of microcephaly, and limited causal reference on pregnant women. We made analog comparison of severe acute respiratory syndrome and chikungunya virus in terms of DNA mutation and global movement to provide further research recommendation. The chance of catch-up growth may decrease the number of pervious "diagnosed" microcephaly.
CONCLUSIONSThere are some evidence available through mice models and direct isolation of ZIKV in affected pregnancies on kindly causal relationship but not convincible enough. We analyzed and presented the weakness or limitation of published reports with the desire to shed light to further study directions.
Animals ; Female ; Humans ; Microcephaly ; diagnosis ; etiology ; genetics ; Mutation ; Pregnancy ; Zika Virus ; pathogenicity ; Zika Virus Infection ; complications
8.Diagnosis and counseling for a Chinese pedigree affected with autosomal recessive primary microcephaly 5 due to variants of ASPM gene.
Yan ZHANG ; Lina ZENG ; Li LIN
Chinese Journal of Medical Genetics 2022;39(4):405-408
OBJECTIVE:
To detect potential mutation of the ASPM gene in a Chinese pedigree affected with autosomal recessive primary microcephaly 5 (MCPH5).
METHODS:
Peripheral venous blood samples were collected from the proband and her parents. Amniotic fluid sample was also collected upon her mother' s subsequent pregnancy. Following extraction of genomic DNA, PCR and Sanger sequencing were carried out to identify potential variants of the ASPM gene.
RESULTS:
The proband was found to harbor compound heterozygous variants of the ASPM gene, namely c.8214dupT (p.Q2739fs) in exon 18 and c.9541C>T (p.R3181X) in exon 23, which were respectively inherited from her father and mother. The fetus has found to have inherited the c.9541C>T (p.R3181X) variant only.
CONCLUSION
The c.8214dupT (p.Q2739fs) and c.9541C>T (p.R3181X) compound heterozygous variants of the ASPM gene probably underlay the pathogenesis of MCPH5 in this patient. Above finding has enabled genetic counseling and prenatal diagnosis for her family.
China
;
Counseling
;
Female
;
Humans
;
Microcephaly
;
Mutation
;
Nerve Tissue Proteins/genetics*
;
Pedigree
;
Pregnancy
9.Clinical and genetic analysis of a child with mental retardation and microcephaly with pontine and cerebellar hypoplasia.
Ziwei WANG ; Chuang LI ; Yan ZHAO ; Ling LI ; Yuan LYU ; Hong CUI
Chinese Journal of Medical Genetics 2021;38(10):985-988
OBJECTIVE:
To analyze the clinical phenotype and pathogenic variant in a child diagnosed with mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH).
METHODS:
Clinical phenotype of the child was reviewed. Whole exome sequencing was carried out for the child. Candidate variant was verified by Sanger sequencing of the family member.
RESULTS:
The proband manifested dyskinesia, development delay, cerebellar hypoplasia and bilateral hearing impairment. WES results revealed that the proband has carried a pathogenic c.1641_1644delACAA (p.Thr548Trpfs*69) variant of the CASK gene, which was verified by Sanger sequencing to be a de novo variant.
CONCLUSION
The c.1641_1644delACAA (p.Thr548Trpfs*69) variant of the CASK gene probably underlay the MICPCH in the proband. Above finding has provided a basis for genetic counseling. WES should be considered for the diagnosis of neurological dysplasia.
Cerebellum/abnormalities*
;
Child
;
Developmental Disabilities
;
Family
;
Humans
;
Mental Retardation, X-Linked
;
Microcephaly/genetics*
;
Nervous System Malformations
10.Analysis of a case with Mowat-Wilson syndrome due to nonsense variant of ZEB2 gene.
Mingcong SHE ; Zhenhua ZHAO ; Panlai SHI ; Shanshan GAO ; Xiangdong KONG
Chinese Journal of Medical Genetics 2022;39(8):889-892
OBJECTIVE:
To explore the genetic basis for a girl with distinctive facial features, epilepsy, intellectual disability, chronic constipation and hypopigmentation of neck and upper extremities.
METHODS:
Whole exome sequencing was carried out for the proband. Candidate variant was verified by Sanger sequencing.
RESULTS:
The proband was found to harbor a heterozygous nonsense c.586G>T (p.Glu196*) variant of the ZEB2 gene, which was unreported previously. The variant was not detected in either parent.
CONCLUSION
The ZEB2 gene c.586G>T (p.Glu196*) variant probably underlay the Mowat-Wilson syndrome in this patient. Hypopigmentation in the neck and upper extremities may be related to Mowat-Wilson syndrome. Prenatal diagnosis was recommended for subsequent pregnancies.
Facies
;
Female
;
Hirschsprung Disease
;
Humans
;
Hypopigmentation
;
Intellectual Disability/genetics*
;
Microcephaly
;
Pregnancy
;
Zinc Finger E-box Binding Homeobox 2/genetics*