Molecular genetics research of a Chinese family carrying triple HLA-A alleles / 中国输血杂志

【Objective】 To determine molecular basis of a rare HLA-A typing results carrying triple A alleles in potential allo-HSCT donor and her family. 【Methods】 HLA-A, -B, -C, -DRB1, -DQB1, -E, -F, -G of 5 members in the family were genotyped at a high-resolution level using next-generation sequencing (NGS). HLA-A of probosita was re-checked using polymerase chain reaction-sequence-based typing (PCR-SBT), and SNP oligonucleotide probes (SNP-array)were scanned with genomic DNA of probosita. 【Results】 There was 162.9Kb duplication in 6p22.1(29, 803, 377-29, 966, 301)of probosita who carried triple A alleles A*02∶01∶01, A*11∶01∶01, A*24∶02∶01. Other two family members were found to carry this haplotype: A*02∶01∶01, A*24∶02∶01, B*54∶01∶01, C*01∶02∶01, DRB1*04∶05∶01, DQB1*04∶01∶01, E*01∶01∶01∶03, F*01∶01∶01, G*01∶01∶01∶01, which as a Mendelian gene was segregated and stably transmitted through two generations. 【Conclusion】 Tiny gene duplication induces one haplotype carries two HLA-A alleles in a potential healthy donor for allo-transplantaion and stably transmits through two generations.Routine HLA typing laboratories should pay more attention to this situation and accurately report.

Genotype-environment interaction on arterial stiffness: A pedigree-based study / 北京大学学报(医学版)

OBJECTIVE@#To utilized the baseline data of the Beijing Fangshan Family Cohort Study, and to estimate whether the association between a healthy lifestyle and arterial stiffness might be modified by genetic effects.@*METHODS@#Probands and their relatives from 9 rural areas in Fangshan district, Beijing were included in this study. We developed a healthy lifestyle score based on five lifestyle behaviors: smoking, alcohol consumption, body mass index (BMI), dietary pattern, and physical activity. The measurements of arterial stiffness were brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). A variance component model was used to determine the heritability of arterial stiffness. Genotype-environment interaction effects were performed by the maximum likelihood methods. Subsequently, 45 candidate single nucleotide polymorphisms (SNPs) located in the glycolipid metabolism pathway were selected, and generalized estimated equations were used to assess the gene-environment interaction effects between particular genetic loci and healthy lifestyles.@*RESULTS@#A total of 6 302 study subjects across 3 225 pedigrees were enrolled in this study, with a mean age of 56.9 years and 45.1% male. Heritability of baPWV and ABI was 0.360 (95%CI: 0.302-0.418) and 0.243 (95%CI: 0.175-0.311), respectively. Significant genotype-healthy diet interaction on baPWV and genotype-BMI interaction on ABI were observed. Following the findings of genotype-environment interaction analysis, we further identified two SNPs located in ADAMTS9-AS2 and CDH13 might modify the association between healthy dietary pattern and arterial stiffness, indicating that adherence to a healthy dietary pattern might attenuate the genetic risk on arterial stiffness. Three SNPs in CDKAL1, ATP8B2 and SLC30A8 were shown to interact with BMI, implying that maintaining BMI within a healthy range might decrease the genetic risk of arterial stiffness.@*CONCLUSION@#The current study discovered that genotype-healthy dietary pattern and genotype-BMI interactions might affect the risk of arterial stiffness. Furthermore, we identified five genetic loci that might modify the relationship between healthy dietary pattern and BMI with arterial stiffness. Our findings suggested that a healthy lifestyle may reduce the genetic risk of arterial stiffness. This study has laid the groundwork for future research exploring mechanisms of arterial stiffness.

Methods and Research Hotspots of Forensic Kinship Testing / 法医学杂志

Kinship testing is widely needed in forensic science practice. This paper reviews the definitions of common concepts, and summarizes the basic principles, advantages and disadvantages, and application scope of kinship analysis methods, including identity by state (IBS) method, likelihood ratio (LR) method, method of moment (MoM), and identity by descent (IBD) segment method. This paper also discusses the research hotspots of challenging kinship testing, complex kinship testing, forensic genetic genealogy analysis, and non-human biological samples.

Prenatal genetic diagnosis of increased fetal nuchal translucency in two pregnancies of a woman from polycystic kidney disease pedigree / 中华围产医学杂志

This paper reported a woman with polycystic kidney disease who had increased fetal nuchal translucency (NT) in her two sequential pregnancies. The fetal NT thickness in the first pregnancy was 5.1 mm at 12 +5 weeks of gestation, and the infant was born prematurely at 32 gestational weeks. However, the baby girl died due to respiratory insufficiency and severe asphyxia. The NT thickness in the present pregnancy was 5.7 mm at 12 weeks of gestation. Whole-exome sequencing (WES) and Sanger sequencing confirmed that the dead infant and the current fetus carried compound heterozygous variants of maternal c.4255_4256del and paternal c.18366+2T>C in NEB gene, both were pathogenic variants. The current fetus was diagnosed with arthrogryposis multiplex congenita 6 (AMC6). After genetic counseling, the pregnant woman chose to terminate the pregnancy. The pregnant woman was diagnosed as having polycystic kidney disease type 1 caused by large deletions in exons 25-43 of PKD1 gene by WES combined with multiplex ligation-dependent probe amplification technology.

Genetic analysis of homologous Robertsonian translocation trisomy 21 in 12 pedigrees / 中华围产医学杂志

Objective:To analyze the genetic features of homologous Robertsonian translocation trisomy 21.Methods:This retrospective analysis involved 12 pedigrees in which singleton fetuses were prenatally diagnosed with homologous Robertsonian translocation trisomy 21 [46,XX/XY,+21,der(21;21)(q10;q10)] at the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2012 to January 2023. Moreover, karyotype analysis results of the parental peripheral blood were obtained. The prenatal diagnosis results and genetic features in the 12 pedigrees were summarized using descriptive statistical analysis.Results:Among the 12 pedigrees, eight cases were de novo and the other four were maternally inherited. Three mothers in the four inherited cases had homologous Robertsonian translocation trisomy 21 and the other one was a homologous Robertsonian translocation carrier. The karyotypes of the four fathers were all normal. There were three families with multiple children, two of the couples with normal karyotypes had normal children, and the other couple had a child with homologous Robertsonian translocation trisomy 21 that was inherited from the mother with the same type of trisomy 21. Non-invasive prenatal testing was performed in two pedigrees during this pregnancy and the results showed that one case was at low risk and one was at high risk of trisomy 21. Further testing of the placenta after labor induction confirmed the low-risk case with low proportion of mosaic trisomy 21 (the proportion was 21% on the maternal side of the placenta and 9% on the fetal side). Conclusions:Most cases of homologous Robertsonian translocation trisomy 21 are de nove and few are inherited. Parents of probands with homologous Robertsonian translocation trisomy 21 should be routinely advised to undergo peripheral blood chromosome examination to find out whether they are carriers of homologous Robertsonian translocation.

Characteristics analysis of families of retinal vascular disease with leukoencephalopathy and systemic damage / 中国神经精神疾病杂志

Objective To investigate the clinical data,brain pathology and molecular genetic characteristics of retinal vascular disease families with leukoencephalopathy and systemic damage.Methods The clinical data of two families of RVCL-S(retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations,RVCL-S)were collected and family maps were drawn to analyze the clinical manifestations,imaging,brain pathology and molecular genetic characteristics.Results Family 1:there were 3 male cases and the age of onset was 10 years,29 years and 40 years,respectively.Family 2:there was one male case and the age of onset was 32 years.Both families presented with retinal vascular disease,leukoencephalopathy and multi-system damage,the latter including liver,kidney and digestive tract involvement.There were 4 asymptomatic carriers in two families.The cranial CT of family 1-Ⅱ2 showed lamellar low density near the posterior corner of the left ventricle with multiple intracranial high density calcification.Brain MRI plain scan showed lateral ventricle lesions.The brain MRI plain and enhancement scans of family 1-I5 showed frontotemporal cortex lesions with peripheral edema and space occupying effect,and the ring enhancement was remarkable.The brain MRI plain scan and enhancement scan of family 2-Ⅱ1 showed the right and left frontal lobe lesions,accompanied by peripheral edema and enhancement,and the occupying effect was obvious.The operative pathology of brain tissue from family 1-I5 showed endothelial cell hyperplasia.The pathological manifestations of family 2-Ⅱ1 encephalopathy were consistent with"cerebral infarction"after two operations.The small blood vessels in the small intestinal wall showed endothelial cell proliferation.Molecular genetics:TREX1 D272Rfs heterozygous mutation was present in family 1-Ⅱ2,and his offspring including two daughters and one son were asymptomatic mutation carriers.TREX1 S246Ifs heterozygous mutation was detected in the 2-Ⅱ1 gene of the family which was not found in either the father or the mother found the mutation,and the son was asymptomatic carrier of the mutation.Conclusion The main clinical manifestations of RVCL-S are retinal vascular disease,nervous system involvement and multi-system damage.Imaging findings showed that intracranial lesions were space-occupying,accompanied by peripheral edema and enhancement.The pathological features were small vessel endothelial cell proliferation and lumen stenosis.Genetic results confirmed the presence of TREX1 gene mutation.

Clinical and genetic characteristics of two families with myotonic dystrophy type I / 中华神经医学杂志

Objective:To investigate the clinical and genetic characteristics of families with myotonic dystrophy type I.Methods:Two families with myotonic dystrophy type I admitted to Department of Neurology, First Affiliated Hospital of He'nan University of Science and Technology in September and October 2021 were chosen; their clinical data were retrospectively analyzed. The muscle pathological changes were confirmed by electromyography and muscle MRI. Repeat-primed PCR assay was used to detect the number of CTG repeats in the 3' end non-coding region of DMPK gene. Results:Clinical heterogeneity existed among the two families of patients; muscle weakness and muscular atrophy of the skeletal muscle were the main clinical manifestations; limb weakness, axe face, percussion myotonia and myoglobular sign were noted; systemic multi-system symptoms included palpitation and chest tightness, cataracts, gastrointestinal symptoms, fatigue/lethargy, and cognitive impairment. Electromyography showed myotonic potential and myogenic damage. Muscle fatty infiltration and atrophy were noted in muscle MRI, and lesions were predominantly in the gastrocnemius. All patients had abnormal amplification of DMPK gene CTG (number of CTG repeats> 50 or 100). Conclusion:In addition to skeletal muscle involvement, systemic multi-system involvement such as cardiac, eye, respiratory, endocrine, and nervous system should also be noted by clinicians in patients with myotonic dystrophy type I.

Clinical and molecular genetic study of a Chinese Han family with X-linked retinoschisis / 中华实验眼科杂志

Objective:To study the clinical phenotype and molecular genetic characteristics of a Chinese Han family with X-linked retinoschisis (XLRS), and to determine the associated gene variations.Methods:A pedigree investigation was performed.The clinical characteristics and pedigree analysis of a Han Chinese family line with XLRS was conducted in August 2021 at the Xiamen Eye Center Affiliated to Xiamen University.All patients and the carriers underwent comprehensive medical history collection and routine ophthalmological examinations, including visual acuity, non-contact tonometer, slit lamp microscope, direct ophthalmoscope, and optical coherence tomography.The proband and some patients underwent medical optometry, fundus photography or wide-angle fundus photography, and electroretinogram examination.Peripheral venous blood samples were collected from the family members, and whole exome sequencing (WES) analysis was performed on the proband samples.For variants screened by WES, the expanded verification in other patients and normal persons in the family was carried out by Sanger sequencing.Multiple bioinformatic tools were used to analyze the pathogenicity of variants.This study protocol was approved by the Ethics Committee of Xiamen Eye Center of Xiamen University (No.XMYKZX-KY-2021-012). Written informed consent forms were obtained from each subject or guardian of minors.CADD, FATHMM and other bioinformatics tools were used to analyze the pathogenicity of the variation sites.Results:The Han XLRS pedigree consisted of 8 individuals in 3 generations.Out of the 3 cases diagnosed with XLRS based on clinical evaluation, all were male.The mother of the proband was a carrier of related genes.There were 5 persons with normal phenotypes.There was no history of consanguineous marriages within the family, and the disease was shown to be intergenerational, which is consistent with the recessive inheritance of the X chromosome.None of the patients had a history of systemic disease or any other abnormal manifestations.The prevailing feature of ophthalmopathy was poor binocular vision since childhood.The proband and his younger brother had spoke split in the macula, and their grandfather showed atrophy of retinal nerve fibers.Genetic analysis revealed a hemizygous variation c. 214G>C: p.Glu72Gln in the RS1 gene in all the patients in this family.The proband's mother was heterozygous at this site, and all other phenotypically normal family members exhibited wild type at this site.This variant was predicted to be a deleterious variation and likely to cause disease based on bioinformatics analysis. Conclusions:The proband and patients in this Han Chinese family have the known c. 214G>C: p.Glu72Gln hemizygous variation of the RS1 gene and exhibit mild XLRS, which was consistent with the recessive inheritance of X chromosome.

SPTLC2 gene mutation leads to intermediate Charcot-Marries-Tooth disease: a family report / 中华神经科杂志

Objective:To report a SPTLC2 gene mutation in a family with a phenotype of Charcot-Marie-Tooth disease.Methods:To screen the family of patients with pathogenic mutations of SPTLC2 gene from the database of hereditary peripheral neuropathy in the Department of Neurology, Peking University First Hospital, and to collect their clinical data, peripheral nerve conduction examination, nerve ultrasound examination, pathological examination of the peroneal nerve and whole exome sequencing results of prohand.Results:One family was screened, the proband was a 16-year-old female with 4 years of sensory loss and anhidrosis of both lower limbs and 16 months of walking difficulty who admitted to Peking University First Hospital in January 2022. Physical examination showed sensory loss, dry skin and weakness in distal limbs. Her father had numbness and dry skin in the distal lower limbs from childhood,weakness and atrophy of his lower limbs in adulthood. He died at age of 52 years old. The nerve conduction study revealed no action potentials of the sensory and motor nerves of the lower limbs in the proband. The amplitude of the compound muscle action potential of the motor conduction of the bilateral ulnar nerve and median nerve decreased, and the nerve conduction velocity of the bilateral median nerve were 32 m/s and 24 m/s. Neurosonography showed thickening of peripheral nerves. Sural biopsy revealed severe loss of myelinated and unmyelinated nerve fibers with onion bulbs formation. SPTLC2 gene showed a known heterozygous p.G435V mutation. The lower limb weakness was improved after oral L-serine.Conclusions:SPTLC2 gene mutation can lead to an intermediate Charcot-Marie-Tooth disease phenotype. L-serine can improve the limb weakness.

Clinical characteristics and genetic analysis of a pedigree with Stargardt disease caused by a novel mutation in ABCA4 gene / 中华检验医学杂志

Objective:To explore the clinical characteristics and genetics of a pedigree with Stargardt disease, and investigate the pathogenicity of ABCA4 (ATP binding cassette subfamily A member 4) gene mutations in Stargardt disease.Methods:The proband was admitted to the Second People′s Hospital of Jinan in May 2021 due to diminution of vision. The proband was diagnosed with Stargardt disease according to the clinical diagnostic criteria of Stargardt disease. Detailed ophthalmological examinations was also performed on family members of the proband. Genomic DNA were extracted from the proband and the family members, and the whole exon sequencing was performed to find pathogenic gene mutations. The hazard of mutations was analyzed by polyphen-2, SIFT and MutationTaster websites. Sanger sequencing was used to verify the mutations. Conserved analysis of homologous species and 3-dimensional (3D) molecular model of the protein were used to analyze the pathogenicity.Results:Ophthalmological examinations showed reduced binocular vision, macular atrophy and "bull′s eye sign" in the proband and there was no abnormal signs and symptoms among the family members. Through whole exon sequencing analysis and Sanger sequencing verification, the compound heterozygous mutations (c.215G>A and c.6563T>C) of ABCA4 gene were co-segregated with this disease in this family. SIFT, Polyphen-2 and MutationTaster predicted that these two mutations were pathogenic. Conservative analysis and 3D molecular model of protein showed that mutations could cause changes in protein structure and affect protein function.Conclusion:The compound heterozygous mutations (C.215G>A and C.6563T>C) of ABCA4 gene are the pathogenic mutations of Stargardt disease in this pedigree.

Identification and pedigree investigation of B(A) and cisAB blood groups / 中国输血杂志

【Objective】 To investigate the serological and molecular genetic characteristics of B(A) and cisAB blood groups discovered in our laboratory. 【Methods】 ABO blood group serology and genetic tests were used to identify blood groups of 6 blood samples, submitted by blood center and hospitals in Shandong, and pedigree investigation was carried on 2 of them. 【Results】 Among the 6 samples, serological results were B(A) in 5 cases and cisAB in 1 case. The results of genetic tests were consistent with the serological results, as the alleles included B(A)04, B(A)02 and cisAB01, and all genotypes were heterozygous with O. Serological pedigree study was conducted on 2 samples: One cisAB patient with his 4 relatives(cisAB type father and three O type relatives) and one B(A)02/O1 donor with his 3 relatives[ B(A) type father/brother and O type mother). For B(A)02/O1 donor, the results of genetic testing were consistent with the serological results, as the paternal genotype was the same as that of the proband, the younger brother was B(A)02/O2, and the maternal genotype was O1/O2. 【Conclusion】 The cisAB and B(A) blood groups are often indistinguishable by serological phenotypes and require genetic confirmation. CisAB pedigree investigation revealed 2 cases of cisAB blood type and B(A) pedigree investigation revealed 3 cases of B(A). The genotyping of cisAB and B(A) in this region were cisAB01/O2, B(A)02/O1, B(A)02/O2, B(A)04/O1 and B(A)04/O2. B(A)and cisAB subtypes can be accurately identified through genetic testing and pedigree investigation, which can provide a reliable basis for blood transfusion selection and ensure the safety of clinical blood transfusion.

Molecular genetic analysis and predigree of a new FUT1 allele of para-Bombay blood group: a case report / 中国输血杂志

【Objective】 To study the serological and molecular mechanism of a case of para-Bombay blood group caused by 236delG mutation of FUT1 gene and investigate the pedigree. 【Methods】 The ABO, H and Lewis antigens of the proband and her family members were detected serologically, and the ABO blood group was confirmed by gene testing. The FUT1 gene was amplified by PCR and then sequenced. The structure of FUT1 236delG enzyme of the proband was simulated in 3D by SwissModel online server. 【Results】 Serological results showed that the proband was rare para-Bombay ABhm, Le(a-b-). Her father and mother was type A and type B, respectively. The gene results showed that the proband was type AB, while her father and mother was type A and type B, respectively. The sequencing results showed that the proband had 236delG/551_552delAG gene mutation, while her mother had 236delG FUT1 gene mutation, and her father had 551_552delAG FUT1 gene mutation. The 3D simulation of the enzyme structure of the proband FUT1 236delG showed that the translated product was an alpha helix structure with no actual function. 【Conclusion】 The 236delG mutation is a new discovered mutation in FUT1 genotype, with 551_ 552delAG mutation(FUT1* 01N.06 genotype), which can result in the generation of para-Bombay blood group.

Frequency of JK (a-b-) in Yichang: genetic pedigree analysis of Jk (a-b-) and Jka weak expression / 中国输血杂志

【Objective】 To explore the molecular hereditary and frequency of Jk(a-b-) in blood donors in Yichang. 【Methods】 A total of 49 999 samples from Yichang Red Cross Central Blood Station were screened for Jk(a-b-) by urea hemolysis test(2 mol /L). The phenotypes of JK (a-b -) probands and their families were confirmed by monoclonal anti-Jka and anti-Jkb, and the whole exon of SLC14A1 gene was sequenced. 【Results】 The frequency of Jk(a-b-) in Yichang blood donors was 0.004% (2/49 999), and the exon sequencing of SLC14A1 gene confirmed that both two probands were JK*02N.01 caused by c. 342-1G>A homozygous mutation.Besides, JK*01W.01 allele was observed in the pedigree analysis, and weak expression of Jka was found in 4 out of 11 family members. 【Conclusion】 The frequency of JK (a-b -) in Yichang blood donors is similar to those in Shanghai 0.004%(2/48 400), and both caused by JK * 02N.01 allele with high frequency in Southeast Asia. The epidemiological survey of JK * 01w.01 allele frequency should be further performed.

Familial aggregation myelodysplastic syndromes/acute myeloid leukemia: report of 3 pedigrees and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical characteristics, gene mutation, treatment and prognosis of familial aggregation myelodysplastic syndromes/acute myeloid leukemia (MDS/AML).Methods:The 3 familial aggregation MDS/AML admitted to Shanghai Yangpu District Hospital from August 2012 to March 2019 were collected. The bone marrow examination, gene mutation detection, therapeutic effect and prognosis of the patients were retrospectively analyzed, and the relevant literature was reviewed.Results:In pedigree 1, the survival time of 2 AML patients was 8 months and 1 month, respectively. In pedigree 2, the transformation time of 2 patients diagnosed MDS to AML/high-risk MDS was 4 and 3 months, the survival time was 5 and 8 months, respectively. TP53 and RUNX1 mutations were detected in the older brother. In pedigree 3, the survival time of the AML patient was 13 months, and the MDS patient was stable.Conclusions:Familial aggregation MDS/AML has rapid progression and short survival time, and its diagnosis needs to be combined with family history, cytogenetics, and molecular biology.

A case report of familial renal cell carcinoma / 中华泌尿外科杂志

A total of 4 patients with renal cancer were admitted to our hospital from October 2006 to September 2015 in a familial renal cancer family. Among the 4 patients, 1 patient showed unilateral multiple clear cell carcinoma, 1 patient showed bilateral multiple clear cell carcinoma, and 2 patients showed bilateral multiple chromophobe cell carcinoma. No mutation of VHL or FLCN gene was found in all patients by genetic analysis.

Phenotype and genetic studies of the cases with ATXN2 intermediate-length CAG-repeat expansion in spinocerebellar ataxia type 2 pedigree / 中华神经科杂志

Objective:To explore the phenotype and molecular genetic features of spinocerebellar ataxia type 2 (SCA2) cases with ATXN2 intermediate-length CAG-repeat expansion.Methods:Fragment analysis by capillary electrophoresis was performed to detect the dynamic mutations in the samples of the probands in 1 383 pedigrees with autosomal dominant inherited ataxia in Research Center for Motor Disorders and Neurogenetic Diseases, Department of Neurology, China-Japan Friendship Hospital from 2005 to 2018. The clinical and genetic features of individuals carrying the ATXN2 intermediate-length CAG-repeat expansion were carefully analyzed.Results:Two hundred and three individuals (including the probands and members of their families) in 163 families carried the expanded CAG repeats in ATXN2 gene, among which 107 individuals in 93 families carried the intermediate-length CAG-repeats. Within 20 parent-child pairs, the CAG repeats increased 0-28 copies in 16 pairs with paternal inheritance, and 0-4 copies in 4 pairs with maternal inheritance.Conclusions:For suspected SCA2 cases, ATXN2 gene testing should be performed on the parental members and adult offspring members in the family. Dynamic mutations testing is essential to identify the individuals with ATXN2 intermediate-length repeat expansion, which is very important for genetic counseling.

Childhood onset spinocerebellar ataxia type 2: a family report and literature review / 中华神经科杂志

Objective:To investigate the clinical characteristics, genetic characteristics and diagnosis of spinocerebellar ataxia type 2 (SCA2) patients with childhood onset.Methods:The clinical data of a SCA2 pedigree who diagnosed at Neurogenetic Metabolic Disease Clinic of Children′s Hospital Affiliated to Zhengzhou University in July 2019 were collected, and the reported cases of childhood-onset SCA2 were reviewed. The CAG repeat of ATXN2 gene was detected by polymerase chain reaction, capillary gel electrophoresis and Sanger sequencing techniques.Results:A total of 9 people in 4 generations of the family were affected, showing an autosomal dominant inheritance. The proband was a 3 years and 4 months old boy, who showed abnormal symptoms at 9 months which manifested as developmental retardation. At 1 year old, he developed progressive regression which represented neither to be amused, recognize others, stand and walk alone, nor had language development. Meanwhile, he had difficulty swallowing, long-term constipation, and a history of convulsions. His sister and mother were not yet sick. His grandmother could not walk, had slurred speech accompanied by nystagmus, and magnetic resonance imaging showed cerebellar atrophy. His granduncles and grandaunts had unstable walking and dysarthria. His great-grandfather required wheelchair to walk. This pedigree showed an autosomal dominant inheritance. One of the ATXN2 gene alleles of the proband, his sister, mother and grandmother all showed abnormal amplification with 99, 55, 44, and 43 times respectively and no inserting CAA sequence. A total of 14 literatures reported 20 cases of childhood-onset SCA2 patients who were genetically diagnosed. The majorities had onset in infancy, and few can develop into school age. The main clinical manifestations were developmental delay, dystonia or insufficiency, myoclonus or infantile spasms, motor retardation, abnormal eye movement, retinitis pigmentosa and dysphagia, while the classic cerebellar syndrome was only partially present. Abnormal rhythm was found on electroencephalogram, cerebellar atrophy on magnetic resonance imaging or CT of the head.Conclusions:This case is the youngest genetically-confirmed SCA2 patient reported in China. Reported patients usually have onset in infancy with excessive repeat sequence expansion. Their clinical characteristics are different from the classic patients and could only be diagnosed by dynamic mutation detection.

Focusing on prenatal genetic counseling and proper option of genetic testing methods / 中华围产医学杂志

More and more new technologies are being applied to prenatal diagnosis as the development of genetic testing technology advances. Pedigree analysis and phenotype recognition are the foundation of prenatal genetic counseling and diagnosis. In addition, fully understanding the advantages and disadvantages of different genetic testing techniques, developing a rationale, standardized and sequential testing strategy for the affected family, and analyzing the underlying genetic etiology and prognosis are critical for prenatal diagnosis and achieving the goal of birth defect prevention.

Pedigree analysis for prenatal screening and diagnosis / 中华围产医学杂志

The information arising from pedigree analysis is important for clinicians to understand the inheritance pattern of the disease, filter the testing data, and provide suggestions to other family members. Along with the development and clinical implementation of new genetic testing, an increasing number of "positive" results are obtained and pedigree analysis is required to further verify the pathogenicity.

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.