OBJECTIVE: To analyze the clinical and genetic characteristics of a boy featuring unexplained developmental delay, malnutrition and distinct facial appearance. METHODS: Physical examination was carried out for the child. Peripheral blood samples were collected from the child and his parents for the extraction of genomic DNA and trio-whole exome sequencing. Candidate variants were verified by Sanger sequencing. RESULTS: The patient had facial dysmorphism including nasal alae aplasia, scalp defect and teeth deformities, in addition with recurrent diarrhea due to pancreatic exocrine insufficiency. DNA sequencing revealed that he has harbored compound heterozygous variants of the UBR1 gene, namely c.3167C>G (p.S1056X) and c.1911+14C>G, which were inherited from his father and mother, respectively. Database search has suggested the c.3167C>G to be a novel nonsense variant and c.1911+14C>G a known splicing variant. Based on the guidelines of the American College of Medical Genetics and Genomics, the two variants were predicted to be pathogenic and likely pathogenic, respectively. CONCLUSION The child was diagnosed with Johanson-Blizzard syndrome due to the compound heterozygous variants of the UBR1 gene. Above finding has enriched the mutational spectrum of the UBR1 gene and provided a basis for genetic counseling for this family.
Child ; Humans ; Male ; Ectodermal Dysplasia/genetics* ; Pancreatic Diseases/genetics* ; Ubiquitin-Protein Ligases/genetics*

Objective: To investigate the clinical phenotypes and genotypic spectrum of exocrine pancreatic insufficiency in children with cystic fibrosis. Methods: This was a retrospective analysis of 12 children with cystic fibrosis who presented to Children's Hospital of Fudan University from December 2017 to December 2021. Clinical features, fecal elastase-1 level, genotype, diagnosis and treatment were systematically reviewed. Results: A total of 12 children, 7 males and 5 females, diagnosis aged 5.4 (2.0, 10.6) years, were recruited. Common clinical features included chronic cough in 12 cases, malnutrition in 7 cases, steatorrhea in 7 cases, bronchiectasis in 5 cases and electrolyte disturbance in 4 cases. Exocrine pancreatic insufficiency were diagnosed in 8 cases,the main clinical manifestations were steatorrhea in 7 cases, of which 5 cases started in infancy; 6 cases were complicated with malnutrition, including mild in 1 case, moderate in 2 cases and severe in 3 cases; 3 cases had abdominal distension; 2 cases had intermittent abdominal pain; 4 cases showed fatty infiltration or atrophy of pancreas and 3 cases showed no obvious abnormality by pancreatic magnetic resonance imaging or B-ultrasound. All 8 children were given pancreatic enzyme replacement therapy, follow-up visit of 2.3 (1.2,3.2) years. Diarrhea significantly improved in 6 cases, and 1 case was added omeprazole due to poor efficacy. A total of 20 variations of CFTR were detected in this study, of which 7 were novel (c.1373G>A,c.1810A>C,c.270delA,c.2475_2478dupCGAA,c.2489_c.2490insA, c.884delT and exon 1 deletion). Conclusions: There is a high proportion of exocrine pancreatic insufficiency in Chinese patients with cystic fibrosis. The main clinical manifestations are steatorrhea and malnutrition. Steatorrhea has often started from infancy. Pancreatic enzyme replacement therapy can significantly improve the symptoms of diarrhea and malnutrition.
Cystic Fibrosis/genetics* ; Diarrhea/complications* ; Exocrine Pancreatic Insufficiency/genetics* ; Female ; Genotype ; Humans ; Male ; Malnutrition/complications* ; Pancreatic Diseases/genetics* ; Phenotype ; Retrospective Studies ; Steatorrhea/genetics*

OBJECTIVETo study clinical features and gene mutations in Shwachman-Diamond syndrome (SDS), a rare autosomal recessive disease, in children.

METHODClinical manifestations, laboratory examinations, image studies, and genetic testing of two cases with SDS were presented, analyzed, and discussed; 311 SDS cases from the related literature since 2004 were reviewed.

RESULT(1) The two cases both presented with characteristic exocrine pancreatic insufficiency evidenced by abnormal pancreas on imaging and growth retardation, persistent or intermittent neutropenia (<1500×10(6)/L) and/or anemia, and skeletal abnormalities. Analysis of the SBDS gene revealed the same compound heterozygous genotype (c.183_184TA > CT, c.258+2T > C) for both subjects. This genotype is the result of the inheritance of abnormal alleles from both healthy parents. (2) Among 311 cases, 75 cases having complete clinical data were characterized by exocrine pancreatic dysfunction (61/75; 81.3%), hematologic abnormalities with single- or multi-lineage cytopenia (64/75; 85.3%), and bone abnormalities (47/75; 62.7%). c.183_184TA > CT, c.258+2T > C, and c. [ 183_184TA > CT; 258+2T > C] are the major types of SBDS gene mutation(85/138;61.6%).

CONCLUSIONSDS is characterized by exocrine pancreatic dysfunction with malabsorption, malnutrition, and growth failure; hematologic abnormalities with single- or multi-lineage cytopenia, and bone abnormalities. The diagnosis of SDS relies on a combination of clinical features and gene-based tests. The SDS patients need long term follow-up and management.

Bone Marrow Diseases ; diagnosis ; genetics ; Child ; DNA Mutational Analysis ; Exocrine Pancreatic Insufficiency ; diagnosis ; genetics ; Exons ; Genes, Recessive ; Heterozygote ; Humans ; Infant ; Lipomatosis ; diagnosis ; genetics ; Male ; Mutation ; Neutropenia ; Proteins ; genetics

Bone Marrow Diseases ; diagnosis ; genetics ; therapy ; Child, Preschool ; Exocrine Pancreatic Insufficiency ; diagnosis ; genetics ; therapy ; Female ; Humans ; Infant ; Lipomatosis ; diagnosis ; genetics ; therapy ; Male ; Mutation

BACKGROUNDCystic fibrosis (CF) is rare in Chinese. We investigated the mutations in the gene of cystic fibrosis transmembrane conductance regulator (CFTR) in a Chinese CF patient and reviewed the clinical features, gene mutations in Chinese CF cases.

METHODSBlood samples were collected from a previously reported CF girl and her parents. The 24 coding exons of CFTR of the proband were amplified and sequenced.

RESULTSA Chinese girl of 16 years old was diagnosed as CF at the age of 14. She had recurrent productive cough with bronchiectasis in bilateral upper lobes, parasinusitis and otitis media, but without pancreatic involvement. Her sweat chloride was (108.9 +/- 3.3) mmol/L. A heterozygous novel missense mutation of 699 C --> A which results in the amino acid change of N189K was identified in exon 5. In addition, a heterozygous 3821 - 3823 delT mutation in exon 19 was found in CFTR. The mutation 699C --> A was inherited from her father, and the 3821 - 3823 delT mutation was from her mother. Twenty patients with CF in Chinese reported from 1974 to 2004 were also reviewed. DelF508 mutation was not found in the nine cases whose CFTR mutations were analyzed.

CONCLUSIONSThe CF proband carries two heterozygous mutations (699C --> A and 3821 - 3823 delT) in CFTR. 699C --> A mutation is a novel mutation which is not reported previously. Review of reported Chinese cases suggests that the genotype of Chinese CF may be different from those of white cases. More studies are needed to understand the spectra of CFTR and clinical CF features in Chinese.

Adolescent ; Cystic Fibrosis ; complications ; genetics ; Cystic Fibrosis Transmembrane Conductance Regulator ; genetics ; Exocrine Pancreatic Insufficiency ; etiology ; Female ; Humans ; Mutation, Missense ; Respiratory Tract Diseases ; etiology

OBJECTIVETo study the clinical characteristics and diagnosis of the Johanson-Blizzard syndrome.

METHODThe clinical characteristics and diagnosing procedure of 1 case with Johanson-Blizzard syndrome were analyzed, and genetic analysis was made in diagnosing procedure, and 28 cases of Johanson-Blizzard syndrome with detailed clinical data were reviewed and analyzed.

RESULTA one year and nine months old girl, who was initially admitted to the hospital because of fatty diarrhea and increased frequency of defecation. Imperforate anus, and aplastic alae nasi was noticed after birth. On physical examination, short stature, mental retardation, tooth abnormalities and scalp defects were observed. Fat globule was found by routine stool test. Serum biochemistry showed an exocrine and endocrine pancreatic insufficiency, CT scan of the abdomen demonstrated fatty replacement of the pancreas, UBR1 gene analysis showed heterozygous for two missense changes. In all 29 cases, exocrine pancreatic insufficiency (72.4%) and hypoplasia of the alae nasi (93%) were the most common clinical manifestations, and sensorineural hearing loss (59%), scalp defects (69%) and hair thinning or upsweep of the hair (44.8%), hypothyroidism (44.8%), absence of permanent teeth (44.8%) and imperforate anus (21%) were also very common, but did not include consanguineous marriage of parents (10.3%).

CONCLUSIONJohanson-Blizzard syndrome is a rare autosomal recessive multisystem disorder, it is characterized by the association of congenital exocrine pancreatic insufficiency and hypoplasia or aplasia of the nasal wings, and can be diagnosed by clinical characteristics and UBR1 gene analysis.

Anus, Imperforate ; Deafness ; diagnosis ; genetics ; pathology ; Ectodermal Dysplasia ; diagnosis ; genetics ; pathology ; Female ; Growth Disorders ; Hearing Loss, Sensorineural ; Humans ; Hypothyroidism ; diagnosis ; genetics ; pathology ; Infant ; Intellectual Disability ; Nose ; abnormalities ; pathology ; Pancreatic Diseases ; diagnosis ; genetics ; pathology ; Ubiquitin-Protein Ligases ; genetics

Abnormalities, Multiple ; genetics ; pathology ; Child, Preschool ; Chromosome Aberrations ; Diagnosis, Differential ; Diarrhea ; diagnosis ; etiology ; therapy ; Exocrine Pancreatic Insufficiency ; complications ; Fever ; diagnosis ; etiology ; Fingers ; abnormalities ; Humans ; Male ; Pancreatic Diseases ; etiology ; Syndrome

No abstract available.
Adolescent ; Base Sequence ; Bone Marrow Diseases/*diagnosis/diagnostic imaging/genetics ; DNA Mutational Analysis ; Exocrine Pancreatic Insufficiency/*diagnosis/diagnostic imaging/genetics ; Humans ; Lipomatosis/*diagnosis/diagnostic imaging/genetics ; Magnetic Resonance Imaging ; Male ; Mutation ; Proteins/genetics ; Tomography, X-Ray Computed

Adaptor Proteins, Signal Transducing ; genetics ; Bone Marrow Diseases ; genetics ; pathology ; DNA Mutational Analysis ; DNA-Binding Proteins ; genetics ; Exocrine Pancreatic Insufficiency ; genetics ; pathology ; Glucose-6-Phosphatase ; genetics ; Humans ; Leukocyte Elastase ; genetics ; Lipomatosis ; genetics ; pathology ; Mutation ; Neutropenia ; congenital ; genetics ; Proteins ; genetics ; Transcription Factors ; genetics

Several species of Helicobacter colonize the hepatobiliary tract of animals and cause hepatobiliary diseases. The aim of this study is to investigate Helicobacter found in the biliary tract diseases of humans. Thirty-two bile samples (15 from bile duct cancer, 6 from pancreatic head cancer, and 11 from intrahepatic duct stone) were obtained by percutaneous transhepatic biliary drainage. Polymerase chain reaction analysis using Helicobacter specific urease A gene and 16S rRNA primers, bile pH measurement, and Helicobacter culture were performed. Helicobacter DNA was detected in 37.5%, and 31.3% by PCR with ureA gene, and 16S rRNA, respectively. The bile pH was not related to the presence of Helicobacter. The cultures were not successful. In conclusion, Helicobacter can be detected in the bile of patients with bile duct diseases. The possibility of pathogenesis of biliary tract diseases in humans by these organisms will be further investigated.
Adenocarcinoma/microbiology ; Adult ; Aged ; Aged, 80 and over ; Bile/microbiology* ; Bile Duct Diseases/microbiology* ; Bile Duct Neoplasms/microbiology ; Cholelithiasis/microbiology ; DNA Primers ; DNA, Bacterial* ; Helicobacter/isolation & purification* ; Helicobacter/growth & development ; Helicobacter/genetics ; Human ; Hydrogen-Ion Concentration ; Middle Age ; Pancreatic Neoplasms/microbiology ; Polymerase Chain Reaction