Identification of 1q21.1 microduplication in a family:A case report

BACKGROUND Copy number variation(CNV)has become widely recognized in recent years due to the extensive use of gene screening in developmental disorders and epilepsy research.1q21.1 microduplication syndrome is a rare CNV disease that can manifest as multiple congenital developmental disorders,autism spectrum disorders,congenital malformations,and congenital heart defects with genetic heterogeneity.CASE SUMMARY We reported a pediatric patient with 1q21.1 microduplication syndrome,and carried out a literature review to determine the correlation between 1q21.1microduplication and its phenotypes.We summarized the patient’s medical history and clinical symptoms,and extracted genomic DNA from the patient,her parents,elder brother,and sister.The patient was an 8-mo-old girl who was hospitalized for recurrent convulsions over a 2-mo period.Whole exon sequencing and whole genome low-depth sequencing(CNV-seq)were then performed.Whole exon sequencing detected a 1.58-Mb duplication in the CHR1:145883867-147465312 region,which was located in the 1q21.1 region.Family analysis showed that the pathogenetic duplication fragment,which was also detected in her elder brother’s DNA originated from the mother.CONCLUSION Whole exon sequencing combined with quantitative polymerase chain reaction can provide an accurate molecular diagnosis in children with 1q21.1 microduplication syndrome,which is of great significance for genetic counseling and early intervention.

Townes–Brocks syndrome with adult renal impairment in a Chinese family:A case report

BACKGROUND Townes–Brocks syndrome(TBS)is a rare autosomal dominant syndrome that is characterized by a triad of imperforate anus,dysplastic ears,and thumb malformations.Heterozygous variants of SALL1 are responsible for this syndrome.Renal structural abnormalities and functional impairments are often reported in TBS patients.CASE SUMMARY We report a case of TBS in a Chinese family.The index patients showed obvious renal atrophy and renal failure.TBS was suggested after a physical examination and pedigree analysis.Whole exome sequencing revealed a heterozygous variant of SALL1.The variant(NM_001127892 c.1289_c.1290 insC)led to a read-frame shift of the encoded protein,which was confirmed by Sanger sequencing.The variant cosegregated with the phenotype among affected members.CONCLUSION A novel variant in SALL1 gene may be the molecular pathogenic basis of this disorder.

CCNO mutation as a cause of primary ciliary dyskinesia:A case report

BACKGROUND Primary ciliary dyskinesia(PCD)is an uncommon and genetically diverse condition.According to reports,most patients had more than 50 visits before being diagnosed with PCD,and the age at diagnosis was mostly in preschool,with an average age of about(10.9±14.4)years old.CCNO is a pathogenic gene that regulates the cell cycle,and its mutation is linked to the uncommon human genetic disorder PCD.Although the prevalence of the CCNO mutation is regarded to be exceptionally low,new reports of this mutation have increased in comparison to prior ones.PCD patients with CCNO are rare,and the incidence rate is no more than 2%in whole PCD patients.CASE SUMMARY Here,we report a case of a young Chinese woman diagnosed with PCD,who was found to carry the CCNO gene by whole exon gene sequencing.In this case,a young non-smoking Chinese female exhibiting recurrent cough and sputum at birth.Chest computed tomography(CT)showed bronchiectasis with infection,and sinus CT showed chronic sinusitis.However,the patient had no visceral transposition and no history of infertility.Under electron microscope,it was found that cilia were short and reduced in number,and no power arm of cilia was observed.Whole exon sequencing analysis of the genome of the patient showed that the patient carried CCNO pathogenic gene,exon c.303C>A nonsense mutation and c.248_252dup frameshift mutation.Her clinical symptoms and CT images were improved after two months of treatment with aerosol inhalation and oral azithromycin.CONCLUSION The results showed that CCNO is an important cause of PCD.More mutant genes that may contribute to genetically diverse disorders like PCD have been discovered as sequencing technology has advanced.Furthermore,the increase of genetic information makes it easier to diagnose uncommon diseases in clinical practice.

Novelα-galactosidase A gene mutation in a Chinese Fabry disease family:A case report

BACKGROUND Fabry disease(FD)is a rare X-linked lysosomal storage disease caused by a deficiency of the enzymeα-galactosidase A.CASE SUMMARY Herein,we analyzed a four-generation Chinese family.The proband is a 57-yearold woman who was diagnosed with left ventricular hypertrophy and atrial fibrillation 7 years ago.Echocardiography showed an end-diastolic diameter of the interventricular septum of 19.9 mm,left ventricular end-diastolic diameter of 63.1 mm,and moderate-to-severe mitral regurgitation.Cardiac magnetic resonance indicated an enlarged left heart and right atrium,decreased left ventricular systolic and diastolic function,a left ventricular ejection fraction of 20%,and thickening of the left ventricular septum.In March 2019,gene and enzyme activity tests confirmed the diagnosis of FD.Her son was diagnosed with FD after gene and enzyme activity assay,and was prescribed agalsidase-βfor enzyme replacement therapy in July 2020.Two sisters of the proband were also diagnosed with FD by genetic testing.Both of them had a history of atrial fibrillation.CONCLUSION A novel mutation was identified in a Chinese family with FD,in which the male patient had a low level of enzyme activity,early-onset,and severe organ involvement.Comprehensive analysis of clinical phenotype genetic testing and enzyme activity testing helped in the diagnosis and treatment of this FD family.