De novo variants in KCNJ3 are associated with early-onset epilepsy.

BACKGROUND: KCNJ3 encodes a subunit of G-protein-coupled inwardly rectifying potassium channels, which are important for cellular excitability and inhibitory neurotransmission. However, the genetic basis of KCNJ3 in epilepsy has not been determined. This study aimed to identify the pathogenic KCNJ3 variants in patients with epilepsy. METHODS: Trio exome sequencing was performed to determine potential variants of epilepsy. Individuals with KCNJ3 variants were recruited for this study. Detailed clinical information and genetic data were obtained and systematically reviewed. Whole-cell patch-clamp recordings were performed to evaluate the functional consequences of the identified variants. RESULTS: Two de novo missense variants (c.998T>C (p.Leu333Ser) and c.938G>A (p. Arg313Gln)) in KCNJ3 were identified in two unrelated families with epilepsy. The variants were absent from the gnomAD database and were assumed to be damaging or probably damaging using multiple bioinformatics tools. They were both located in the C-terminal domain. The amino acid residues were highly conserved among various species. Clinically, the seizures occurred at a young age and were under control after combined treatment. Electrophysiological analysis revealed that the KCNJ3 Leu333Ser and Arg313Gln variants significantly compromised the current activities and exhibited loss-of-function (LOF) effects. CONCLUSION: Our findings suggest that de novo LOF variants in KCNJ3 are associated with early-onset epilepsy. Genetic testing of KCNJ3 in patients with epilepsy may serve as a strategy for precision medicine.

Heterozygous CAPZA2 mutations cause global developmental delay, hypotonia with epilepsy: a case report and the literature review.

CAPZA2 encodes the α2 subunit of CAPZA, which is vital for actin polymerization and depolymerization in humans. However, understanding of diseases associated with CAPZA2 remains limited. To date, only three cases have been documented with neurodevelopmental abnormalities such as delayed motor development, speech delay, intellectual disability, hypotonia, and a history of seizures. In this study, we document a patient who exhibited seizures, mild intellectual disability, and impaired motor development yet did not demonstrate speech delay or hypotonia. The patient also suffered from recurrent instances of respiratory infections, gastrointestinal and allergic diseases. A novel de novo splicing variant c.219+1 G > A was detected in the CAPZA2 gene through whole-exome sequencing. This variant led to exon 4 skipping in mRNA splicing, confirmed by RT-PCR and Sanger sequencing. To our knowledge, this is the third study on human CAPZA2 defects, documenting the fourth unambiguously diagnosed case. Furthermore, this splicing mutation type is reported here for the first time. Our research offers additional support for the existence of a CAPZA2-related non-syndromic neurodevelopmental disorder. Our findings augment our understanding of the phenotypic range associated with CAPZA2 deficiency and enrich the knowledge of the mutational spectrum of the CAPZA2 gene.

[Genetic and clinical analysis of a child with Shwachman-Diamond syndrome due to compound heterozygous variants of SBDS gene].

OBJECTIVE: To analyze the clinical features and genetic characteristics of a patient with Shwachman-Diamond syndrome (SDS) due to compound heterozygous variants of SBDS gene. METHODS: A female child with SDS who was admitted to the Children's Hospital Affiliated to Zhengzhou University in February 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her elder sister and parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RESULTS: The child, a 1-year-and-1-month-old girl, had mainly manifested with diarrhea, hematochezia, growth retardation and malnutrition, along with increased transaminases and decreased neutrophils and hemoglobin. Anteroposterior X-ray of her left wrist indicated significantly delayed bone age. Colonoscopy revealed that her colorectal mucosa was erosive with oily food residues attached to the intestinal lumen. Genetic testing revealed that she has harbored c.258+2T>C and c.100A>G compound heterozygous variants of the SBDS gene. The c.258+2T>C variant has derived from her father and known to be pathogenic, whilst the other has derived from her mother. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.100A>G variant was classified as likely pathogenic (PM1+PM2_Supporting+PM3+PM5+PP3). CONCLUSION: The compound heterozygous variants of c.258+2T>C and c.100A>G probably underlay the SDS in this child. For children with refractory diarrhea, liver damage and growth retardation, SDS should be suspected, and genetic testing can facilitate the diagnosis and treatment.

[Clinical characteristics of children on prolonged mechanical ventilation due to different primary diseases]. / ä¸åŒåŽŸå‘ç— å¯¼è‡´é•¿æœŸæœºæ¢°é€šæ°”æ‚£å„¿çš„ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To investigate the differences in clinical characteristics among children on prolonged mechanical ventilation (PMV) due to different primary diseases. METHODS: A retrospective analysis was performed on the clinical data of 59 pediatric patients requiring PMV from July 2017 to September 2022. According to the primary disease, they were divided into respiratory disease (RD) group, central nervous system (CNS) group, neuromuscular disease (NMD) group, and other disease group. The four groups were compared in terms of general information, treatment, and outcome. RESULTS: There were significant differences among the four groups in age, body weight, Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score, Pediatric Risk of Mortality III (PRISM Ⅲ) score, analgesic and sedative treatment, nutrition supply, rehabilitation treatment, tracheotomy, successful ventilator weaning, and outcomes (P<0.05). Compared with the RD group, the CNS group and the other disease group had a significantly higher age and a significantly higher proportion of children receiving rehabilitation treatment, and the CNS group had a significantly higher proportion of children receiving tracheotomy (P<0.008). Compared with the other disease group, the CNS group and the NMD group had significantly lower PELOD-2 and PRISM III scores, and the CNS group had a significantly higher proportion of children with successful ventilator weaning and a significantly higher proportion of children who were improved and discharged (P<0.008). CONCLUSIONS: There are differences in clinical characteristics among children receiving PMV due to different etiologies. Most children in the RD group have a younger age, and children in the CNS group have a relatively good prognosis.

Clinical and genetic analysis of two patients with primary ciliary dyskinesia caused by a novel variant of DNAAF2.

BACKGROUND: The study describes the clinical manifestations and variant screening of two Chinese siblings with primary ciliary dyskinesia (PCD). They carry the same DNAAF2 genotype, which is an extremely rare PCD genotype in the Chinese population. In addition, the study illustrated an overview of published variants on DNAAF2 to date. METHODS: A two-child family was recruited for the study. Clinical manifestations, laboratory tests, bronchoscopic and otoscopic images, and radiographic data were collected. Whole blood was collected from siblings and their parents for whole-exome sequencing (WES) and Sanger sequencing to screen variants. RESULTS: The two siblings exhibited typical clinical manifestations of PCD. Two compound heterozygous variants in DNAAF2 were detected in both by WES. Nonsense variant c.156 C>A and frameshift variant c.177_178insA, which was a novel variant. CONCLUSION: The study identified a novel variant of DNAAF2 in Chinese children with a typical phenotype of PCD, which may enrich our knowledge of the clinical, diagnostic and genetic information of DNAAF2-induced PCD in children.

[Analysis of clinical phenotypes and MMACHC gene variants in 65 children with Methylmalonic acidemia and homocysteinemia].

OBJECTIVE: To carry out Sanger sequencing for MMACHC gene variants among 65 Chinese pedigrees affected with combined methylmalonic aciduria and homocysteinemia, and summarize their genetic and clinical characteristics and prognosis. METHODS: Clinical characteristics of the 65 children identified with Methylmalonic acidemia and homocysteinemia at the Children's Hospital Affiliated to Zhengzhou University (Zhengzhou Children's Hospital) from April 2017 to April 2022 were selected as the study subjects. Potential variants of the MMACHC gene were detected by direct sequencing of the PCR products. RESULTS: The median age of the 65 children was 3 months (14 days to 17 years old). These included 28 cases (43.08%) from neonatal screening, 11 cases (16.92%) with a history of jaundice, and 9 cases (13.85%) with various degrees of anemia. The main clinical symptoms included development delay, slow growth, epilepsy, hydrocephalus, lethargy, feeding difficulty, regression or decline in motor ability, recurrent respiratory infections, anemia, jaundice, respiratory and heart failures, hydrocephalus, limb weakness, and hypertension. Blood and urine tandem mass spectrometry screening has revealed increase of methylmalonic acid, propionyl carnitine, propionyl carnitine/acetylcarnitine ratio, and propionyl carnitine/free carnitine ratio to various extents, and blood homocysteine was increased in all patients. The detection rate of genetic variants was 98.46% (128/130), and in total 22 types of MMACHC gene variants were detected. The most common ones have included c.609G>A (W203X) (58/128), c.658-660del (K220del) (19/128), and c.80A>G (Q27A) (16/128). Two novel variants have been identified, namely c.565C>T (p.R189C) and c.624_ 625delTG (p.A208Afs), which were respectively predicted as likely pathogenic (PM2_Supporting+PM3+PP2+PP3) and pathogenic (PVS1+PM2_Supporting+PM3+PP2) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Exon 4 had the highest frequency for the detection. CONCLUSION: Identification of MMACHC gene variants has confirmed the diagnosis in the children, among which the c.609G>A variant has the highest frequency. Discovery of the new variants has enriched the mutational spectrum of the MMACHC gene.

[Clinical characteristics and genetic analysis of two children with Tuberous sclerosis complex].

OBJECTIVE: To explore the clinical characteristics and genetic variants in two children with Tuberous sclerosis complex (TSC). METHODS: Two children who had presented at the Children's Hospital Affiliated to Zhengzhou University respectively in June 2020 and July 2021 were selected as the study subjects. Clinical data of the children were collected, and potential pathogenic variants were screened by whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of their family members. RESULTS: Child 1 was a 7-month-and-29-day-old male, and child 2 was a 2-year-and-6-month-old male. Both children had shown symptoms of epileptic seizures and multiple hypomelanotic macules. Genetic testing revealed that both children had harbored de novo variants of the TSC2 gene, namely c.3239_3240insA and c.3330delC, which were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION: This study has uncovered the genetic etiology for two children with TSC. Above findings have also enriched the phenotypic and mutational spectrum of TSC in the Chinese population.

[Analysis of CLCN4 gene variant in a child with Raynaud-Claes syndrome].

OBJECTIVE: To analyze the clinical phenotype and genetic variant in a child with Raynaud-Claes syndrome (RCS). METHODS: A child who was diagnosed with RCS at the Children's Hospital Affiliated to Zhengzhou University for delayed language and motor development in August 2022 was selected as the study subject. Clinical data of the child were collected, and potential genetic variant was detected by next-generation sequencing and Sanger sequencing. The pathogenicity of the candidate variant was analyzed. RESULTS: The child, a 4-year-and-4-month-old male, has manifested global developmental delay, speech disorders, special facial features and behavioral abnormalities. Genetic testing revealed that he has harbored a hemizygous c.1174C>T (p.Gln392Ter) variant of the CLCN4 gene, which was not detected in either of his parents. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION: The c.1174C>T (p.Gln392Ter) variant of the CLCN4 gene probably underlay the PCS in this child. Above finding has expanded the mutational spectrum of the CLCN4 gene and enabled genetic counseling and prenatal diagnosis for his family.

Genetic analysis and identification of novel variations in Chinese patients with pediatric epilepsy by whole-exome sequencing.

OBJECTIVES: We aimed to investigate the genetic etiology of epilepsy in children, and to analyze the nature of genetic variation, the function of related genes, and the genotype-phenotype relationship. Moreover, the impact of the genetic diagnosis on prognosis and prenatal diagnosis will be discussed. METHODS: We recruited 218 pediatric epilepsy patients with onset ages ranging from postnatal 5 days to 3 years during a three-year collection period. WES was conducted only for the probands to screen for possible candidate genes. RESULTS: A total of 55 patients (25.2%) had positive genetic diagnoses. Autosomal dominant gene variants were the most common (34/55; 61.8%) and de novo variants (31/34; 91.2%) consistent with an autosomal dominant mode of inheritance. Among 64 variants identified in 35 genes, 33 (51.6%) were novel, previously unreported. Ion channel genes play critical roles in the pathogenesis of epilepsy, accounting for 58.8% (20/34) of the variants. A total of 31 (56.4%) families chose to have a prenatal diagnosis in subsequent pregnancies based on the genetic diagnosis. CONCLUSION: Our data suggest that applying WES in patients with epilepsy of unknown etiology can improve counseling and management. Early establishment of genetic diagnosis was necessary for counseling on recurrence risk and prenatal diagnosis. A large number of unreported variants were detected, widening the known spectrum of genetic variation related to epilepsy risk.

[Clinical characteristics and genetic analysis of a Chinese pedigree affected with mitochondrial DNA depletion syndrome due to compound heterozygous variants of RRM2B gene].

OBJECTIVE: To analyze the clinical characteristics and pathogenic gene in a Chinese pedigree affected with mitochondrial DNA depletion syndrome 8A (MTDPS8A). METHODS: Whole exome sequencing was carried out for the patient. Sanger sequencing was used to verify the results, and PolyPhen-2 and PROVEAN software were used to predict the impact of amino acid changes on the function of the protein. RESULTS: The patient, a two-month-old female, was admitted to the hospital for poor milk intake and poor mental response. Her clinical manifestations included feeding difficulty, shortness of breath and low muscle tone. Auxiliary laboratory test indicated that the infant was underdeveloped with abnormal liver, kidney, and heart functions accompanied by hyperlacticacidemia. She responded poorly to treatment and eventually died. Sequencing revealed that the child has carried compound heterozygous missense variants of the RRM2B gene, namely c.16delA (p.R6Gfs*22) and c.175G>C (p.A59P), which were respectively inherited from her father and mother, and both were newly discovered pathologic variants. CONCLUSION: The c.16delA and c.175G>C compound heterozygous variants of the RRM2B gene probably underlay the pathogenesis of MTDPS8A. Above finding has strengthened the understanding of the clinical feature and genetic etiology of this disease and expanded the mutation spectrum of the RRM2B gene.

[Clinical and genetic analysis of two rare male patients with Rett syndrome].

OBJECTIVE: To conduct clinical and genetic analysis of two male patients with atypical Rett syndrome. METHODS: Collection of clinical data in the two patients and these parents; whole exome sequencing (WES) was used to detect the potential variants, which were verified by Sanger sequencing. X chromosome inactivation (XCI) detection is performed in the Patient 1's mother to detect the allelic expression difference of the MECP2 gene. RESULTS: Patient 1, a 5-year and 10-month-old boy, had mental disorders and mild intellectual disability (ID) (IQ: 54), whose mother had ID. Patient 2 was a 9-month and 18-day-old male presented with recurrent infections, respiratory insufficiency, hypotonia and global developmental delay. WES indentified a hemizygous mutation, c.499C>T (p.R167W), in the MECP2 gene in patient 1, which was inherited from his mother. The inactivation of X chromosome is skewed, and the expression ratio of wild-type and mutant MECP2 is 100%:0. Patient 2 was found a de novo splicing mutation, c.62+2_62+3del in the MECP2 gene. They were both reported pathogenic variant related to Rett syndrome. c.499C>T (p.R167W) was defined as likely pathogenic (PS1+PM2+PP3) and c.62+2_62+3del was pathogenic (PVS1+PM2+PM6) based on American College of Medical Genetics and Genomics standards and guidelines. CONCLUSION: Both the two patients were diagnosed with rare male Rett syndrome, which had atypical clinical manifestations and large difference. Above foundings have revealed novel phenotypes in Chinese male patients with Rett syndrome.

[Phenotypic and genetic analysis of a case with hypohidrotic ectodermal dysplasia due to Xq13.1 microdeletion].

OBJECTIVE: To investigate the clinical phenotype and genetic characteristics of a patient with hypohidrotic ectodermal dysplasia (HED) due to partial deletion of EDA gene. METHODS: The child has presented with HED complicated with epilepsy. Family trio whole exome sequencing (Trio-WES), copy number variation sequencing (CNV-seq), and karyotype analysis were carried out to explore the underlying genetic etiology. RESULTS: The proband, a 7-year-and-8-month-old boy, presented with thin curly hair, thin and sparse eyebrow, xerosis cutis, susceptibility to hyperthermia from childhood, hypohidrosis, sharp/sparse/absent teeth, saddle nose, prominent forehead, auricle adulation and seizure. He was found to have a normal chromosomal karyotype, and no abnormality was found by Trio-WES. Genome-wide CNV-seq revealed a 341.90 kb deletion at Xq13.1q13.1 (chrX: 68 796 566-69 138 468). As verified by PCR-electrophoresis, the deletion has removed part of the EDA gene. The deletion was derived from his mother with normal hair, mild xerosis cutis, and sparse, decidulated and nail-like teeth. The mother was detected with a heterozygous 242.10 kb deletion at Xq13.1q13.1 (chrX: 68 836 154-69 078 250). CONCLUSION: Both the proband and his mother have carried a Xq13.1 microdeletion involving part of the EDA gene. The clinical phenotypes of the mother and the proband were consistent with the clinical characteristics of X-linked recessive HED, for which partial deletion of the EDA gene is probably accountable.

[Phenotypic and genetic analysis of a boy with a 10p15.3 deletion and partial trisomy 18p syndrome].

OBJECTIVE: To delineate the nature and origin of chromosomal aberration in a girl with mental retardation. METHODS: Genomic DNA was analyzed by using single nucleotide polymorphism-based array (SNP array). The proband and her parents were subjected to routine G-banded chromosomal karyotyping analysis. RESULTS: SNP array has identified a 1.2 Mb microdeletion at 10p15.3 and a duplication at 18p11.21-pter in the proband. The patient was also found to harbor a structural aberration involving 10p. The karyotype of her father was 46,XY,t(10;18)(p15;p11.2), while her mother was found to be normal. CONCLUSION: The structural aberration of 10p carried by the patient has derived from her father whom has carried a balanced translocation of t(10;18). Her karyotype was finally determined as 46,XX,der(10)t(10;18)(p15;p11.2)pat. The abnormal phenotype of the patient can probably be attributed to the presence of 10p15.3 microdeletion and 18p11.21-pter duplication.

[Genetic screening and prenatal diagnosis in 18 high-risk families with 21-hydroxylase deficiency].

OBJECTIVE: Genetic screening and prenatal diagnosis was performed in eighteen families with high risk of 21-hydroxylase deficiency (21-OHD) to provide valuable information for genetic counseling in these affected families. METHODS: First, multiplex ligation-dependent probe amplification (MLPA) combined with nested-PCR based Sanger sequencing was used to detect CYP21A2 gene mutations in probands and their parents of eighteen families, with seven probands had been dead. Second, paternity test was applied to exclude the possibility of maternal genomic DNA contamination, and fetal prenatal diagnosis is based on the mutations found in proband or parents of the family. RESULTS: Ten mutations were identified in these eighteen families, including large fragment deletion, I2G, E3del8bp, I172N, V281L, E6 cluster, L307Ffs, Q318X, R356W and R484Pfs. All probands were caused by homozygous or compound heterozygous mutations of CYP21A2 gene and their parents were carriers. By comparing short tandem repeat sites contamination of maternal genomic DNA was not found in fetal DNA. Prenatal diagnosis showed that five fetus were 21-OHD patients, four fetus were carriers and the other nine fetus were normal. CONCLUSION: CYP21A2 gene mutation is the etiology of 21-OHD. Genetic testing of CYP21A2 could assist physicians in 21-OHD diagnosis and provided genetic counseling and prenatal diagnosis for parents who are at risk for having a child with congenital adrenal hyperplasia.

[Phenotype and genetic analysis of a pedigree affected with progressive familial intrahepatic cholestasis].

OBJECTIVE: To explore the genetic etiology for a pedigree affected with progressive familial intrahepatic cholestasis (PFIC). METHODS: Target sequence capture and next generation sequencing (NGS) were applied for the proband. PCR and Sanger sequencing were used to verify the suspected mutation in his sister with similar symptoms and his parents. RESULTS: The proband and his sister manifested after birth with symptoms including jaundice, pruritus and developmental retardation. NGS has identified compound heterozygous mutations of ABCB11 gene, which encodes bile salt export pump protein (BSEP), namely c.2494C>T (p.Arg832Cys) and c.3223C>T (p.Gln1075*), in the proband, which were inherited from his father and mother respectively. His sister carried the same compound mutations. CONCLUSION: Based on the phenotype and genetic testing, the patients were diagnosed as PFIC2 caused by mutation of the ABCB11 gene. The c.3223C>T is a novel nonsense mutation which may cause premature termination of translation. Above results have enriched the spectrum of ABCB11 mutations and provided new evidence for the molecular basis of PFIC, which also facilitated genetic counseling for this pedigree.

Molecular genetic characterization of cblC defects in 126 pedigrees and prenatal genetic diagnosis of pedigrees with combined methylmalonic aciduria and homocystinuria.

BACKGROUND: We sought to analyse MMACHC variants among 126 pedigrees with cobalamin (cbl) C deficiency and combined methylmalonic aciduria and homocystinuria by Sanger sequencing, characterize the spectrum of MMACHC gene variants, and perform prenatal genetic diagnosis by chorionic villus sampling among these pedigrees. METHODS: Peripheral blood was collected from 126 probands and their parents who visited the Genetic Counseling Clinic at our hospital between January 2014 and December 2017, and DNA was extracted from the blood. Then, we amplified the coding sequence and splicing regions of the MMACHC gene by PCR, and the PCR products were further sequenced to detect the variants in each pedigree. In 62 families, pregnant women were subjected to chorionic villus sampling for prenatal genetic diagnosis. RESULTS: In total, 31 distinct variants were detected in the 126 pedigrees, and the most frequent variants were c.609G > A (p.Trp203Ter), c.658_660delAAG (p.Lys220del), c.567dupT (p.Ile190Tyrfs*13) and c.80A > G (p.Gln27Arg). Two of these variants have not been previously reported in the literature. One variant [c.463_465delGGG (p.Gly155del)] is a small-scale deletion, and the other variant [c.637G>T(p.Glu213Ter)] is a nonsense mutation. Among the 62 pedigrees who received a prenatal diagnosis, 16 foetuses were normal, 34 foetuses were carriers of heterozygous variants, and the remaining 12 foetuses harboured compound heterozygous variants or homozygous variants. Couples whose foetuses were normal or carriers continued the pregnancy, whereas couples whose foetuses harboured compound heterozygous variants or homozygous variants decided to terminate the pregnancy. The follow-up results were consistent with the prenatal diagnosis. CONCLUSIONS: Two novel MMACHC variants were identified, and prenatal genetic diagnosis is an accurate and convenient method that helps avoid the delivery of combined methylmalonic aciduria and homocystinuria patients.

Mutation analysis of the TUBB8 gene in primary infertile women with arrest in oocyte maturation.

Tubulin beta eight class VIII (TUBB8) is a subtype of ß-tubulin that only exists in primates. Mutations in the TUBB8 gene have been proven to cause oocyte maturation arrest. The aim of this study was to identify the new types of mutations in TUBB8. Six women (families) with oocyte maturation arrest and 100 healthy controls were recruited. The sequence of the TUBB8 gene was amplified and analyzed by Sanger sequencing, which revealed a de novo heterozygous variant c.292G > A (p.G98R) of TUBB8 in one affected individual. This TUBB8 variant was absent in the 100 fertile females and was predicted to be highly damaging to the function of the TUBB8 protein by SIFT and PolyPhen-2. This novel variant extends the spectrum of TUBB8 mutations and the presence of a TUBB8 mutation is being considered to be indicative of a poor prognosis for the success of assisted reproductive treatment.

[Analysis of MUT gene mutations and prenatal diagnosis for 20 pedigrees affected with isolated methylmalonic aciduria].

OBJECTIVE: To analyze MUT gene variants among 20 pedigrees affected with isolated methylmalonic aciduria by Sanger sequencing. METHODS: Peripheral blood samples were collected from the 20 probands and their parents. Following DNA extraction, the coding regions of the MUT gene were subjected to PCR amplification and Sanger sequencing. For 9 pedigrees, chorionic villus sampling was performed for prenatal genetic diagnosis. RESULTS: Nineteen variants were detected in the 20 pedigrees, with the most common ones including c.323G to A (p.Arg108His), c.1106G to A (p.Arg369His), c.729_730insTT(p.D244Lfs*39), and c.1107dupT (p.T370Yfs*22). Three variants were not reported previously, which included a small-scale deletion c.920_923delTCTT (p.F307Sfs*6) and two missense mutations c.419T to C (p.Leu140Pro) and 613G to A (p.Glu205Lys). For 9 pedigrees undergoing prenatal diagnosis, 1 fetus was normal, three were found to carry heterozygous mutations, while the remaining 5 fetuses have carried compound heterozygous mutations or homozygous mutations. CONCLUSION: Three novel variants of the MUT gene have been identified.

[Analysis of POMT1 gene mutation in a pedigree affected with congenital muscular dystrophy].

OBJECTIVE To analyze mutation of POMT1 gene in a Chinese family affected with congenital muscular dystrophy (CMD). METHODS Peripheral blood samples of the family including one affected and two unaffected individuals, in addition with chorionic villous sample from the fetus, were collected. PCR was used to amplify exons 19 and 20 of the POMT1 gene, and the products were sequenced directly. Based on the result of genetic testing, prenatal diagnosis of the fetus was attained. RESULTS The proband was found to carry a heterozygous missense mutation c.1939G>A (p.Ala647Thr) in exon 19 of the POMT1 gene inherited from the mother and a heterozygous frameshift mutation c.2141delG (p.Trp714Ter) in exon 20 inherited from the father. Prenatal diagnosis revealed that the fetus has carried the c.1939G>A (p.Ala647Thr) missense mutation. With the disease causing mutation, the fetus was predicted to have similar phenotype as its mother. CONCLUSION The compound heterozygous mutations of c.1939G>A (p.Ala647Thr) and c.2141delG (p.Trp714Ter) probably underlie the CMD in this family. Based on the result, prenatal diagnosis may be provided.

[Genetic and prenatal diagnosis of a retinitis pigmentosa pedigree].

OBJECTIVE: To explore the genetic etiology of a pedigree affected with hereditary retinitis pigmentosa. METHODS: High-throughput DNA sequencing was used to analyze the sequences of 173 genes associated with hereditary eye diseases in the proband. Suspected mutation was verified with PCR amplification and Sanger sequencing. RESULTS: The proband was found to have carried a c.570_571 ins GAAGATGCTGT insertional mutation in the RP2 gene located on the X chromosome. All female carriers of the pedigree were heterozygous, while all affected males were hemizygous for the same mutation. CONCLUSION: The inheritance pattern of this retinitis pigmentosa pedigree was X-linked recessive. The c.570_571 ins GAAGATGCTGT insertional mutation of the RP2 gene probably underlies the disease.