Objective:To investigate the clinical phenotypes, therapy and genetic features of aldehyde dehydrogenase 7 family member A1 (ALDH7A1) gene mutations in five cases of pyridoxine dependent epilepsy (PDE) with diagnosis confirmed by next generation sequencing.Methods:Retrospective analysis was carried out on clinical data of five cases of PDE children with early epilepsy onset who were treated in the Department of Neurology of Children′s Hospital Affiliated to Zhengzhou University from February 2018 to November 2019. Next generation sequencing approach was used for genetic sequencing of proband ALDH7A1 gene and the first generation Sanger was used for validation of family members. And the characteristics of gene mutations were analyzed.Results:Among the five children diagnosed with PDE, the male to female ratio was 4 ∶ 1 and ages at clinic visit ranged from two months to 10 months old. In clinical phenotypes, all five cases experienced onset in neonatal period, with repeated seizures, manifested as myoclonus, spasms or focal paroxysm. The administration of antiepileptic drugs performed poorly in seizure control while long term oral intake of large dose pyridoxine showed better efficacy. All the five cases of children came from compound heterozygous mutations of father and mother, i.e. slicing homozygous mutation c.247-2(IVS2)A>T, missense mutation c.584A>G (p.N195S) and nonsense mutation c.1003C>T(p.R335 *), missense mutation c.1553G>C(p.R518T) and c.1547A>G(p.Y516C), missense mutation c.1547A>G(p.Y516C) and frameshift mutation c.1566_1568delTAC, missense mutation c.1061A>G(p.Y354C) and nonsense mutation c.841C>T(p.Q281X, 259), among which c.247-2(IVS2)A>T was novel splicing site mutation not reported before. Conclusions:PDE is induced by ALDH7A gene mutation. Early clinical manifestations are mostly onset of refractory epilepsy in neonatal period. Antiepileptic drugs perform poorly in terms of efficacy while pyridoxine can control seizure effectively. Gene analysis should be conducted on such patients for confirmed diagnosis.

Objective:To investigate the clinical characteristics and gene mutation of seven cases of CDKL5 gene related early-onset epileptic encephalopathy diagnosed by next-generation sequencing.Methods:The clinical data of children with early-onset epileptic encephalopathy from February 2018 to December 2019 in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University were retrospectively analyzed. The whole exome sequencing method was used to analyze the entire exome of the proband, and seven cases of CDKL5 gene mutation positive were screened out, and Sanger sequencing verification on family members was performed to identify the source and the characteristics of gene mutations were analyzed.Results:Among the seven children diagnosed with CDKL5 gene related early-onset epileptic encephalopathy, the ratio of male to female was 2∶5, and the age of onset was 15 days to five months of birth. The clinical phenotypes all included different degrees of developmental delay and repeated seizures, which were manifested as general seizures, myoclonic seizures, convulsive seizures or focal seizures; the outcome of use of antiepileptic drugs to control seizures was poor, and some applications of ketogenic diet had better effects. CDKL5 gene mutation sites were all denovo mutations, including NM_003159: c.772_776del (p.K258Efs *10) frameshift mutation, NM_003159.2 (exon: 9-15) heterozygous deletion, CDKL5 hemizygous deletion, NM_003159: c.268 (exon5) G>T (p.E90 *, 941) and NM_003159: c.2578C>T (p.Q860 *, 171) nonsense mutation, NM_003159: c.211A>G (p.Asn71Asp) and NM_001323289: c.545T>C (p.L182P) missense mutation. Among them, c.772_776del (p.K258Efs *10), c.268 (exon5)G>T and c.2578C>T (p.Q860 *, 171) have not been reported. Conclusions:CDKL5 gene related early-onset epileptic encephalopathy is an early onset epilepsy, which is more common in women, and has different forms of seizures. The early electroencephalogram is characterized as severe abnormal brain discharge, and the disease progresses in various forms. There are no specific changes in head magnetic resonance imaging. Different gene mutation sites may lead to different phenotypes and prognostic differences. Many anti-epileptic treatments are ineffective, and ketogenic diets are effective for some patients.

Clinical data and genetic mutation characteristics of a patient with Coffin-Siris syndrome by 6q25.3 deletion were summarized. The child was a 7-year and 6-month old girl who had feeding difficulties, repeated infection, language and motor retardation, low intelligence, laryngeal cartilage dysplasia, thick eyebrows, sparse teeth, hairy back, hyperactivity and aggressive behavior, seizures and ataxia. There was no abnormality in chromosomal karyotype analysis by proband; genomic copy number variant sequencing (CNV-seq) indicated approximately 4.27 Mb heterozygous deletion in chromosome 6q25.3 region, with 17 genes including ARID1B gene, father maternal CNV-seq showing no abnormalities. Trio-whole-exome sequencing showed the proband missed all exons 1-20 of the ARID1B gene, with wild-type parents. The proband had severe clinical symptoms and haplodose insufficiency which was the genetic etiology.

Objective:To investigate the clinical phenotype of a child with Jansen-de Vries syndrome, to clarify its genetic diagnosis and genetic characteristics, and to improve the understanding of this disease.Methods:Clinical data from a child with Jansen-de Vries syndrome diagnosed in the Children′s Affiliated Hospital of Zhengzhou University in October 2019 were collected, using core family-complete exon genomics detection (Trio-WES) and chromosome copy number variation (CNV) analysis techniques for genetic testing for the child and her parents, generation Sanger sequencing for family member verification for possible pathogenic mutations, and clinical and molecular genetic analysis. The relevant reports of PPM1D gene mutation in patients with mental retardation were reviewed.Results:The proband was a 11-month-old girl, presenting with mental retardation, lagging speech and motor development, autistic behavior, gastrointestinal dysfunction, and short stature, low flat nose bridge, low ear, short finger syndrome.Trio-WES results of the core family of the child suggested that PPM1D was a new transcoding heterozygous mutation, PPM1D (NM-003620): c.1216delA (p.Thr406Profs *3), and the karyotype and CNV analysis of the chromosome were normal. Literature retrieval showed currently a total of 18 cases were reported PPM1D gene mutation of mental disorders, described in the online human Mendel database for developmental disorder associated with gastrointestinal dysfunction and pain threshold increases, the age distribution in the seven months to 21 years of age, clinical manifestation of mental retardation, increased pain threshold, abnormal behavior, feeding difficulties, visual impairment, short finger syndrome, a group of syndromes associated with short stature, fever or vomiting, and congenital deformities. Conclusions:Jansen-de Vries syndrome clinically presents mainly with overall retardation (mental retardation/backward delayed motor development, language development, low muscle tone), abnormal behavior (lonely sample behavior, autism), craniofacial malformations (broad forehead, low ear nose bridge, thin upper lip), short finger syndrome (short feet, pinky stubby), gastrointestinal dysfunction (milk overflow, feeding difficulties, constipation). The child was diagnosed as a newly transcoding heterozygous mutation of the PPM1D gene. The current treatment is mainly rehabilitation training, and growth hormone replacement therapy can be given to part of the short height disease. The PPM1D gene [PPM1D(NM-003620): c.1216delA(p.Thr406Profs *3)] is the genetic cause of the child.

OBJECTIVE: To evaluate the effectiveness of limited internal fixation combined with a hinged external fixator in the treatment of peri-elbow bone infection. METHODS: The clinical data of 19 patients with peri-elbow bone infection treated with limited internal fixation combined with a hinged external fixator between May 2018 and May 2021 were retrospectively analyzed. There were 15 males and 4 females with an average age of 44.6 years (range, 28-61 years). There were 13 cases of distal humerus fractures and 6 cases of proximal ulna fractures. All the 19 cases were infected after internal fixation of fracture, and 2 cases were complicated with radial nerve injury. According to Cierny-Mader anatomical classification, 11 cases were type Ⅱ, 6 cases were type Ⅲ, and 2 cases were type Ⅳ. The duration of bone infection was 1-3 years. After primary debridement, the bone defect was (3.04±0.28) cm, and the antibiotic bone cement was implanted into the defect area, and the external fixator was installed; 3 cases were repaired with latissimus dorsi myocutaneous flap, and 2 cases were repaired with lateral brachial fascial flap. Bone defects repair and reconstruction were performed after 6-8 weeks of infection control. The wound healing was observed, and white blood cell (WBC), erythrocyte sedimentation rate (ESR), and C-reaction protein (CRP) were reexamined regularly after operation to evaluate the infection control. X-ray films of the affected limb were taken regularly after operation to observe the bone healing in the defect area. At last follow-up, the flexion and extension range of motion and the total range of motion of the elbow joint were observed and recorded, and compared with those before operation, and the function of the elbow joint was evaluated by Mayo score. RESULTS: All patients were followed up 12-34 months (mean, 26.2 months). The wounds healed in 5 cases after skin flap repair. Two cases of recurrent infection were effectively controlled by debridement again and replacement of antibiotic bone cement. The infection control rate was 89.47% (17/19) in the first stage. Two patients with radial nerve injury had poor muscle strength of the affected limb, and the muscle strength of the affected limb recovered from grade Ⅲ to about grade Ⅳ after rehabilitation exercise. During the follow-up period, there was no complication such as incision ulceration, exudation, bone nonunion, infection recurrence, or infection in the bone harvesting area. Bone healing time ranged from 16 to 37 weeks, with an average of 24.2 weeks. WBC, ESR, CRP, PCT, and elbow flexion, extension, and total range of motions significantly improved at last follow-up ( P<0.05). According to Mayo elbow scoring system, the results were excellent in 14 cases, good in 3 cases, and fair in 2 cases, and the excellent and good rate was 89.47%. CONCLUSION Limited internal fixation combined with a hinged external fixator in the treatment of the peri-elbow bone infection can effectively control infection and restore the function of the elbow joint.
Male ; Female ; Humans ; Adult ; Elbow ; Elbow Joint/surgery* ; Retrospective Studies ; Bone Cements ; Treatment Outcome ; External Fixators ; Fracture Fixation, Internal/methods* ; Fractures, Bone ; Range of Motion, Articular