OBJECTIVE: To analyze the clinical and genetic characteristics of a child with clinical manifestations of hypoplasia, epilepsy and abnormal face. METHODS: The clinical data of the child were collected. The peripheral blood samples of the patient and his parents were extracted for high-throughput sequencing, and Sanger sequencing verification and bioinformatics analysis were performed to detect suspected pathogenic variants. RESULTS: The clinical manifestations of the child were overall developmental backwardness, seizures, autism, and special facial appearance. High throughput sequencing showed that there was a heterozygous mutation of exon 11: c.1920_c.1927delCCTCTACC (p.Ser641Rfs*31) of the DYRK1A gene. The same variant was found in neither of her parents, suggesting that it has a denovo origin. CONCLUSION The exon11: c.1920_c.1927delCCTCTACC (p.Ser641Rfs*31) mutation in DYRK1A gene was the genetic etiology of the case, which enriches the pathogenic gene spectrum of DYRK1A and provides the basis for clinical diagnosis and genetic counseling.
Arthrogryposis ; Child ; Facies ; Female ; Heterozygote ; Humans ; Intellectual Disability/genetics* ; Mutation

Adolescent ; Adult ; Aged, 80 and over ; Arthrogryposis ; genetics ; Child ; Female ; Humans ; Male ; Middle Aged ; Pedigree

OBJECTIVE: To explore the genetic basis for a child featuring global developmental delay. METHODS: DNA was extracted from peripheral blood sample taken from the patient and subjected to whole exome sequencing. Suspected variants were verified by Sanger sequencing of his family members. RESULTS: A heterozygous c.239T>C (p.Ile80Thr) variant of the GNB1 gene was detected in the proband, which was a verified to be de novo in origin. CONCLUSION The heterozygous c.239T>C (p.Ile80Thr) variant of the GNB1 gene probably underlay the disease in this child.
Arthrogryposis ; Child ; Family ; GTP-Binding Protein beta Subunits ; Heterozygote ; Humans ; Intellectual Disability/genetics* ; Whole Exome Sequencing

OBJECTIVE: To explore the genetic etiology of two pedigrees affected with congenital arthrogryposis. METHODS: Whole exome sequencing (WES) was used to screen potential variations in the proband. Suspected variations were analyzed with bioinformatics software and validated by Sanger sequencing. RESULTS: A heterozygous c.1123G>A (p.Glu375Lys) variation was detected in the proband and an affected fetus from pedigree 1, while a de novo heterozygous c.118 G>A (p.Val40Met) variation was detected in an affected fetus from pedigree 2. CONCLUSION The two heterozygous variations of the MYH3 gene probably underlie the disease in the pedigrees. Above results have facilitated genetic counseling and prenatal diagnosis.
Arthrogryposis ; Cytoskeletal Proteins ; genetics ; Female ; Heterozygote ; Humans ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Whole Exome Sequencing

OBJECTIVETo delineate the clinical, electrophysiological and genetics features of a family where 4 members were affected with hereditary neuropathy with liability to pressure palsies (HNPP).

METHODSClinical features of the 4 patients were summarized. Electrophysiological examination and genetic analysis were carried out.

RESULTSAll of the patients showed recurrent motor and sensory disturbances after minor traction or constriction. Electrophysiology study revealed that the prolonged latency and reduced conduction velocity of peripheral nerve were general and with multiple sites of affection. The nerve locations liable to entrapment showed conduction block. A deletion mutation of peripheral myelin protein 22 (PMP22) gene was identified by genetic analysis.

CONCLUSIONHNPP usually affects areas where nerves are liable to entrapment, and presents with motor and sensory disturbances of the innervated areas. Electrophysiological study reveals general nervous demyelination. Genetic analysis can clarify the diagnosis of HNPP.

Adult ; Arthrogryposis ; genetics ; physiopathology ; Hereditary Sensory and Motor Neuropathy ; genetics ; physiopathology ; Humans ; Male ; Myelin Proteins ; genetics ; Neural Conduction

Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is an autosomal recessive disorder caused by mutations in the VPS33B or VIPAS39 gene. The aim of this study was to investigate the clinical features and VPS33B gene mutations of an infant with ARC syndrome. A 47-day-old female infant was referred to the hospital with the complaint of jaundiced skin and sclera for 45 days and abnormal liver function for 39 days. The patient had been managed in different hospitals, but the therapeutic effects were unsatisfactory due to undetermined diagnosis. Physical examination showed jaundice of the skin and sclera. Systemic skin was dry with desquamation in the limbs and trunk. There were no positive signs on cardiopulmonary examination. The liver was palpable 2.0 cm under the right subcostal margin. The hips and knees were flexed, and the extension was limited, with low muscular tone in the four limbs. Biochemical analysis demonstrated raised serum total bile acids, bilirubin (predominantly conjugated bilirubin) and transaminases, but the γ-glutamyl transpeptidase level was normal. Routine urine test revealed increased glucose as well as red and white blood cells. On genetic analysis, the infant was proved to be homologous for a VPS33B mutation c.1594C>T(p.R532X). She was definitely diagnosed to have ARC syndrome. Symptomatic and supportive therapy was given, but no improvement was observed, and the infant finally died at 3 months and 29 days of life.
Arthrogryposis ; blood ; genetics ; Bile Acids and Salts ; blood ; Bilirubin ; blood ; Cholestasis ; blood ; genetics ; Humans ; Mutation ; Renal Insufficiency ; blood ; genetics ; Vesicular Transport Proteins ; genetics

Abnormalities, Multiple ; genetics ; Acidosis, Renal Tubular ; genetics ; pathology ; therapy ; Arthrogryposis ; genetics ; pathology ; therapy ; Biopsy ; Carrier Proteins ; genetics ; Cholestasis ; genetics ; pathology ; therapy ; DNA Mutational Analysis ; Humans ; Infant, Newborn ; Mutation ; Syndrome ; Vesicular Transport Proteins ; genetics

Sheldon-Hall syndrome (SHS) is a rare autosomal dominant, inherited arthrogryposis syndrome characterized by multiple congenital contractures of the distal limbs. To date, four genes that encode the skeletal muscle fiber complex have been confirmed as the causative genes. Mutations in MYH3 have been identified most frequently and few cases of SHS caused by TPM2 mutations have been reported worldwide. This report describes, for the first time, a Korean family with two generations of SHS resulting from a rare TPM2 mutation, p.R133W. The affected mother and daughter manifested typical facial features of SHS including a triangular face with downslanting palpebral fissures, small mouth, high arched palate, and prominent nasolabial folds, and showed camptodactyly of fingers and deformities of feet with congenital vertical tali. Generalized myopathy with relative sparing of the slow-twitch muscle fibers was also revealed by electromyography in the affected mother.
Alleles ; Arthrogryposis/*genetics ; Asian Continental Ancestry Group/*genetics ; Exons ; Female ; Finger Phalanges/radiography ; Foot Bones/radiography ; Humans ; Infant, Newborn ; Mutation ; Pedigree ; Phenotype ; Republic of Korea ; Sequence Analysis, DNA ; Tropomyosin/*genetics