ABSTRACT
Objective: To compare clinical and laboratory features between JAK2 exon12 and JAK2 V617F mutated polycythemia vera (PV) . Method: We collected data from 570 consecutive newly-diagnosed subjects with PV and JAK2 mutation, and compared clinical and laboratory features between patients with JAK2 exon12 and JAK2 V617F mutation. Results: 543 (95.3%) subjects harboured JAK2 V617F mutation (JAK2 V617F cohort) , 24 (4.2%) harboured JAK2 exon12 mutations (JAK2 exon12 cohort) , and 3 (0.5%) harboured JAK2 exon12 and JAK2 V617F mutations. The mutations in JAK2 exon12 including deletion (n=10, 37.0%) , deletion accompanied insertion (n=10, 37.0%) , and missense mutations (n=7, 25.9%) . Comparing with JAK2 V617F cohort, subjects in JAK2 exon12 cohort were younger [median age 50 (20-73) years versus 59 (25-91) years, P=0.040], had higher RBC counts [8.19 (5.88-10.94) ×10(12)/L versus 7.14 (4.11-10.64) ×10(12)/L, P<0.001] and hematocrit [64.1% (53.7-79.0%) versus 59.6% (47.2%-77.1%) , P=0.001], but lower WBC counts [8.29 (3.2-18.99) ×10(9)/L versus 12.91 (3.24-38.3) ×10(9)/L, P<0.001], platelet counts [313 (83-1433) ×10(9)/L versus 470 (61-2169) ×10(9)/L, P<0.001] and epoetin [0.70 (0.06-3.27) versus 1.14 (0.01-10.16) IU/L, P=0.002] levels. We reviewed bone marrow histology at diagnosis in 20 subjects with each type of mutation matched for age and sex. Subjects with JAK2 exon12 mutations had fewer loose megakaryocyte cluster (40% versus 80%, P=0.022) compared with subjects with JAK2 V617F. The median follow-ups were 30 months (range 4-83) and 37 months (range 1-84) for cohorts with JAK2 V617F and JAK2 exon12, respectively. There was no difference in overall survival (P=0.422) and thrombosis-free survival (P=0.900) . Conclusions: Compared with patients with JAK2 V617F mutation, patients with JAK2 exon12 mutation were younger, and had more obvious erythrocytosis and less loose cluster of megakaryocytes.
Subject(s)
Adult , Aged , Aged, 80 and over , Bone Marrow/pathology , Exons , Humans , Janus Kinase 2/genetics , Middle Aged , Mutation , Mutation, Missense , Polycythemia Vera/genetics , Young AdultABSTRACT
Epidermal growth factor receptor (EGFR) exon 20 insertion mutations are the third most prevalent activating EGFR mutation in non-small cell lung cancer (NSCLC), accounting for 5%-12% of all EGFR mutations in NSCLC cases. Patients harboring EGFR exon 20 insertion mutations exhibit similar clinical characteristics except for worse prognosis as compared to those with 'classic' EGFR mutations. EGFR exon 20 insertion mutations are considered as a heterogeneous class of alterations that cause different conformational changes in EGFR. The majority of mutations (almost 90% of cases) is positioned in the loop that immediately follows the C-terminal of the C-helix, and the most widely reported subtype of insertion mutations is D770_N771>ASVDN(A767_V769dupASV) with frequency of 21%-28%. NSCLC patients with EGFR exon 20 insertion mutations show primary drug resistance to previously approved EGFR tyrosine kinase inhibitors and are generally insensitive to conventional chemotherapy and immunotherapy. The recently approved targeted drugs Amivantamab and Mobocertinib shift the treatment paradigm for NSCLC patients harboring EGFR exon 20 insertion mutations. There are also several new compounds targeting NSCLC EGFR exon 20 insertion mutations are in development. In this article, we provide a through overview on the treatment development in EGFR exon 20 insertion mutant NSCLC. .
Subject(s)
Antibodies, Bispecific , Carcinoma, Non-Small-Cell Lung/genetics , ErbB Receptors/genetics , Exons , Humans , Lung Neoplasms/genetics , Mutagenesis, Insertional , Mutation , Protein Kinase Inhibitors/therapeutic useABSTRACT
OBJECTIVE@#To explore the molecular reasons of weak expression of B antigen on the red cell.@*METHODS@#Serological test for blood group was carried out, including red cell and plasma grouping, and anti-A1 and anti-H testing, and confirming weak A or B antigens by adsorption and elution. Exons 1-7 were sequenced directly, and one of them was cloned and sequenced.@*RESULTS@#All of the 23 samples showed the weak B antigen by serological method. The alleles of the subgroups were identified by DNA sequencing, including 2 Bel subgroup, 4 B3 subgroup, 14 Bw subgroup, 2 CisAB subgroup and a novel allele. The novel allele showed a nucleotide substitution 662G>A in the exon 7, and the sequence was submitted to Blood Group Antigen Gene Mutation Database, and the novel allele was named Bel10.@*CONCLUSION@#Nucleotide substitution in exon results in blood subgroup, which showed that the antigens were weakened, and Bw phenotype was the most frequently subgroup.
Subject(s)
ABO Blood-Group System/genetics , Alleles , Exons , Genotype , Humans , Nucleotides , PhenotypeABSTRACT
OBJECTIVE@#To explore the genetic basis for a child featuring idiopathic epilepsy and autism.@*METHODS@#Peripheral blood samples of the child and his parents were collected with informed consent for the extraction of genome DNA. Whole exome sequencing was carried out for the family trio. Candidate variants were verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The proband was found to harbor a heterozygous nonsense c.3025C>T (p.Arg1009Ter) variant in exon 7 of the CASR gene exon 7, which may produce a truncated protein. Based on the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be deleterious and classified as possibly pathogenic (PVS1+PM2).@*CONCLUSION@#The c.3025C>T (p.Arg1009Ter) variant of the CASR gene probably underlay the disease in this child.
Subject(s)
Autistic Disorder , Child , Epilepsy/genetics , Exons , Heterozygote , Humans , Receptors, Calcium-Sensing/genetics , Exome SequencingABSTRACT
OBJECTIVE@#To explore the genetic basis for a child with infantile liver failure syndrome type 2 (ILFS type 2).@*METHODS@#Clinical features of the child were analyzed. Next generation sequencing was also carried out for him.@*RESULTS@#The child was found to harbor compound heterozygous variants of the NBAS gene, which included a novel nonsense c.2746A>T (p.R916X, 1456) variant in exon 24 and a missense c.3596G>A (p.C1199Y) mutation in exon 31, which has been associated with ILFS type 2. The two variants were respectively inherited from his father and mother.@*CONCLUSION@#The compound heterozygous variants of c.3596G>A and c.2746A>T of the NBAS gene probably underlay the ILFS type 2 in this child.
Subject(s)
Child , Exons/genetics , Genetic Testing , High-Throughput Nucleotide Sequencing , Humans , Liver Failure , Male , MutationABSTRACT
OBJECTIVE@#To investigate the molecular mechanism of one patient with abnormal serological phenotype in RhD and discuss the transfusion strategy.@*METHODS@#The RhD variant sample was screened from a patient with IgM type anti-D antibody and further determined by three different sources of anti-D antibodies. Ten exons and the adjacent introns of the RHD gene were amplified, purified and sequenced. RhCE phenotypes and RHCE genotypes were detected.@*RESULTS@#The patient with Rh variant showed abnormal results of serological tests. The RHD gene sequence analysis showed that the RHD*01W.01 with a variation (c.809T>G, p.Val270Gly) in exon 6 of the RHD gene was found in the patient. The RhCE phenotype was CcEe. The genotyping results of RHCE were consistent with the serological typing results.@*CONCLUSION@#The Rh variant of the patient is RHD*01W.01, these findings indicate that RhD variants should be analyzed by molecular assays for the sake of safe transfusion.
Subject(s)
Alleles , Blood Transfusion , Exons , Genotype , Humans , Phenotype , Rh-Hr Blood-Group System/geneticsABSTRACT
OBJECTIVES@#To study the characteristics of UGT1A1 gene mutations in Dong neonates in Sanjiang County of Liuzhou and its association with the pathogenesis of hyperbilirubinemia in Dong neonates.@*METHODS@#A prospective analysis was performed on 84 neonates who were diagnosed with unexplained hyperbilirubinemia in the Department of Neonatology, Sanjiang County People's Hospital, from January 2021 to January 2022. Sixty healthy neonates born during the same period were enrolled as the control group. Peripheral blood genomic DNA was extracted for both groups, and UGT1A1 exon 1 was amplified by PCR and sequenced.@*RESULTS@#In the case group, 33 neonates were found to have G71R missense mutation, with a mutation rate of 39%. The case group had a significantly higher frequency of A allele than the healthy control group (21% vs 10%, P<0.05). The risk of hyperbilirubinemia in Dong neonates carrying G71R missense mutation was 2.588 times as high as that in healthy neonates carrying wild-type UGT1A1 gene (P<0.05). Hardy-Weinberg equilibrium testing showed that the UGT1A1 G71R locus was in genetic equilibrium in both groups (P>0.05).@*CONCLUSIONS@#UGT1A1 G71R mutation is a high-frequency gene mutation type in Dong neonates in Sanjiang County, and G71R missense mutation is associated with hyperbilirubinemia in Dong neonates.
Subject(s)
Asian People/genetics , China , Exons , Glucuronosyltransferase/genetics , Humans , Hyperbilirubinemia, Neonatal/genetics , Infant, Newborn , MutationABSTRACT
Abstract The growth hormone receptor (GHR) mediates the effect of growth hormone (GH) on linear growth and metabolism. In humans, it exists as two isoforms differing by the retention or exclusion of exon 3; a full-length GHR isoform (GHRfl) and the exon 3-deleted isoform (GHRd3). The genotypic frequency of this polymorphism was analyzed in several studies and in different human populations. However scarce information in Argentinean population is available. Associations between GHRd3 and growth have been reported previously. Some studies have shown that the presence of GHRd3 polymorphism might be a potential variant that improves growth response to recombinant human GH (rhGH) therapy in patients born small for gestational age (SGA), among others. However, over the years the results have been controversial and inconclusive. Based on this, it would be proposed that variants at the genomic level are not completely reflected at the mRNA level. Our aim was to evaluate the genotypic frequencies (%) of the GHR gene polymorphism (GHRfl/GHRfl; GHRfl/GHRd3; GHRd3/GHRd3) in normal Argentinean population (n = 94) and SGA patients (n = 65), and the expression of these polymorphisms at mRNA level in the fetal side of placenta tissues was analyzed. In addition, their asso ciation with spontaneous postnatal catch-up growth in SGA patients was also evaluated. In this study, we show a significant increment of compensatory growth in small for gestational age children (SGA) associated to the presence of the GHRd3 allele polymorphism. In addition, the expression of GHR in healthy placentas revealed that no alternative splicing mechanism occurs.
Resumen El receptor de la hormona de creci miento (GHR) media la acción de la hormona de crecimiento (GH) en el crecimiento lineal y el metabolismo. En los seres humanos, existen dos isoformas que difieren en la retención (GHRfl) o exclusión del exón 3 (GHRd3). La frecuencia genotípica de este polimorfismo fue analizada en varios estudios y en diferentes poblaciones. Sin embargo, la información disponible en la población argentina es escasa. Se ha reportado anteriormente asociación entre el polimorfismo GHRd3 y el crecimiento. Varios estudios ha n demostrado que la presencia del polimorfismo GHRd3 podría mejorar, en pacientes nacidos pequeños para la edad gestacional, entre otros, la respuesta a la terapia con GH humana recombinante (rhGH). Sin embargo, a lo largo de los años los resultados han sido con trovertidos y no concluyentes. En base a esto, se propondría que las variantes a nivel genómico no se reflejan completamente a nivel del ARNm. Nuestro objetivo fue evaluar la frecuencia genotípica de los polimorfismos del gen del GHR (GHRfl/GHRfl; GHRfl/GHRd3; GHRd3/GHRd3) en la población argentina normal (n = 94) y en niños pequeños para la edad gestacional (n = 65), y se analizó la expresión de estos polimorfismos a nivel de ARNm en la porción fetal de placentas sanas. Además, se evaluó la asociación de este polimorfismo con el cre cimiento postnatal espontáneo en pacientes pequeños para la edad gestacional. En este estudio, mostramos un incremento significativo del crecimiento compensatorio en niños pequeños para la edad gestacional asociado a la presencia del polimorfismo del alelo GHRd3. Además, los ensayos de expresión de GHR en placentas sanas revelaron que no se produciría ningún mecanismo de splicing alternativo.
Subject(s)
Humans , Female , Pregnancy , Child , Receptors, Somatotropin/genetics , Human Growth Hormone , Polymorphism, Genetic , Carrier Proteins , Exons , Gestational AgeABSTRACT
OBJECTIVE@#To detect pathogenic variant in a child featuring Usher syndrome type II.@*METHODS@#Peripheral blood samples of the child and his parents were collected for the analysis of variants of hearing impairment-related genes. The findings were verified in 100 individuals with normal hearing.@*RESULTS@#The child was found to harbor compound heterozygous variants of the USH2A gene, namely c.8224-1G>C in intron 41 and c.5678C>G(p.Ser1893X) in exon 28, which were inherited respectively from his mother and father. Based on the American College of Medical Genetics and Genomics standards and guidelines, both c.8224-1G>C and c.5678C>G(p.Ser1893X) variants of USH2A gene were predicted to be pathogenic(PVS1+PM2+PM3).@*CONCLUSION@#The compound heterozygous variants c.8224-1G>C and c.5678C>G of the USH2A gene probably underlay the disease in this child. Above finding has enriched the spectrum of USH2A gene variants.
Subject(s)
Child , Exons , Extracellular Matrix Proteins/genetics , Family , Humans , Introns , United States , Usher Syndromes/geneticsABSTRACT
OBJECTIVE@#To identify the etiology of a patient with severe symptoms of DMD and to trace its pathogenic gene, so as to provide a basis for genetic counseling and clinical intervention.@*METHODS@#Multiple ligation-dependent probe amplification (MLPA) technique was used to analyze exon deletion/repetitive variant of DMD gene, and further analysis was performed by chromosome G-banding, fluorescence in situ hybridization (FISH) and SNP array analysis.@*RESULTS@#The MLPA results of the proband showed that the exon 1-79 of DMD gene were deleted, the G-banding karyotype of blood sample was 46, XY, and the deletion of the short arm of X chromosome was found by FISH. SNP array results showed that 5.8Mb (29 628 158-35 434 714) deletion occurred in the Xp21.2p21.1 region of X chromosome, and the patient was diagnosed as the contiguous deletion syndrome involving the genes of IL1RAPL, MAGEB1-4, ROB, CXorf2, GM, AP3K7IP, FTHL1, DMD, FAM47A, TMEM47, and FAM47B.@*CONCLUSION@#The exact pathogenic site of this family is the deletion of 5.8 Mb (29 628 158-35 434 714) in the Xp21.2p21.1 region of X chromosome, which can be used for prenatal diagnosis. High resolution SNP array technique plays an important role in detecting potential chromosome abnormalities in patients.
Subject(s)
Dystrophin/genetics , Exons , Female , Gene Deletion , Humans , In Situ Hybridization, Fluorescence , Muscular Dystrophy, Duchenne/genetics , Pregnancy , Prenatal DiagnosisABSTRACT
ABSTRACT The concomitant epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocations in lung adenocancers are very rare scenarios. Until now, 42 cases described in the literature have all been treated by different drugs. There is no overall consensus regarding the treatment for this adenocarcinoma subgroup. We report here a case of lung adenocarcinoma with concomitant EGFR mutation in exon 21 (L858R) and ALK rearrangement in primary tumour, EGFR mutation in exon 21 (L858R) and no ALK rearrangement in its synchronous metastasis. We treated this patient with crizotinib as the second-line therapy (after the first line docetaxel-cisplatin chemotherapy), but no response was obtained. The therapeutic choice for the lung adenocancer patients with concomitant EGFR mutation and ALK rearrangement is unclear. Examination of c-ros oncogene 1 mutation can be used as an indicator in the prediction of the crizotinib treatment success. The ALK mutation may not responsible for the resistance to EGFR-tyrosine kinase inhibitors (TKI), and EGFR-TKI can be initiated to EGFR and ALK dual mutant patients as the first treatment.
Subject(s)
Humans , Female , Middle Aged , Adenocarcinoma/genetics , Genes, erbB-1/genetics , Lung Neoplasms/genetics , Mutation/genetics , Adenocarcinoma/drug therapy , Exons/genetics , Cisplatin/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Docetaxel/therapeutic use , Crizotinib/therapeutic use , Lung Neoplasms/drug therapy , Antineoplastic Agents/therapeutic useABSTRACT
Abstract INTRODUCTION: We evaluated the association between genetic polymorphisms in exon 1 (A/O alleles) and promoter regions at positions -550 (H/L variant, rs11003125) and -221 (X/Y variant, rs7096206) MBL2 and periportal fibrosis regression. METHODS: This was a retrospective cohort study involving 114 Brazilians infected with Schistosoma mansoni, who were subjected to follow-up for three years after specific treatment for schistosomiasis to estimate the probability of periportal fibrosis regression. RESULTS: A risk association was observed between polymorphism at the exon 1 MBL2 and periportal fibrosis regression. CONCLUSIONS: This study suggests that the polymorphism of exon 1 MBL2 may potentially be used to predict periportal fibrosis regression in this population.
Subject(s)
Humans , Animals , Schistosomiasis/genetics , Mannose-Binding Lectin/genetics , Polymorphism, Genetic , Brazil , Exons/genetics , Retrospective Studies , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Genotype , Liver Cirrhosis/geneticsABSTRACT
OBJECTIVE@#To determine the genotype of an individual suspected for Aw through DNA sequencing.@*METHODS@#Serologic testing was carried out with standard methods. Exons 6 and 7 of the ABO genes were amplified by PCR and subjected to direct sequencing or sequenced after gene cloning.@*RESULTS@#Serological testing showed that the forward typing and reverse typing were Aw and A, respectively. DNA sequencing revealed that the individual has carried an Aw allele and an O allele. Haplotype sequencing of each allele has revealed a nt543 variant (543G>C) in the Aw allele.@*CONCLUSION@#The individual was verified as a rare A subtype, which was previously unreported in mainland China.
Subject(s)
ABO Blood-Group System/genetics , Alleles , Exons , Genotype , Humans , PhenotypeABSTRACT
OBJECTIVE@#To identify the pathogenic variants of 4 patients with hemolytic anemia of unknown cause.@*METHODS@#Peripheral blood samples of the patients and their family members were collected to extract DNA. The coding region and splice region in all exons of gene of erythrocyte related diseases were analyzed by using target sequence capture and high-throughput sequencing technology. Suspected pathogenic variants were verified by PCR combined Sanger sequencing technology.@*RESULTS@#Each of the probands was detected two compound heterozygous variants, and CDA II was diagnosed. Six variants were detected in the 4 probands, four variants were reported and the other two were first reported.@*CONCLUSION@#By high-throughput sequencing, gene variant of CDA II be analyzed fast and accurately. It is an effective supplement to convenional diagnostic methods. Furthermore, the novel variant sites have enriched the variant database of the SEC23B gene.
Subject(s)
Anemia, Dyserythropoietic, Congenital/genetics , Exons/genetics , High-Throughput Nucleotide Sequencing , Humans , Mutation , Vesicular Transport Proteins/geneticsABSTRACT
OBJECTIVE@#To explore the clinical features and genetic basis for a patient diagnosed with creatine deficiency syndrome (CDS).@*METHODS@#The patient was subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. The level of creatine was determined by using a magnetic resonance spectrum (MRS) method.@*RESULTS@#The patient presented with development delay and poor response to stimuli. No obvious abnormality was found with his muscle tone and strength of his limbs. Borderline EEG was detected. MRI showed abnormal development of the white matter and dysplasia of corpus callosum. Urine organic acid screening has shown increased glycerin-3-phosphate. WES revealed that the patient has carried compound heterozygous variants of the GAMT gene, namely c.412C>T and IVS4-1G>A, which were respectively derived from his mother and father. MRS showed reduced creatine in bilateral basal ganglia. Functional study of the splicing site suggested that the IVS4-1G>A variant has resulted skipping of exon 5 upon splicing.@*CONCLUSION@#The compound variants of the GAMT gene probably underlay the disease in this child. Above finding has enriched the spectrum of GAMT gene variants.
Subject(s)
Child , Creatine , Exons , Humans , Mutation , Syndrome , Exome SequencingABSTRACT
OBJECTIVE@#To establish a method for rapid detection and typing of NPM1 mutations in acute myeloid leukemia (AML) by fluorescence melting curve analysis technology.@*METHODS@#A pair of primers and a fluorescent single-stranded probe (molecule beacon) were designed for the mutant genes mutA, mutB, mutD in exon 12 of nucleopsin (NPM1) and wild type. With a real-time qPCR, the A, B, and D gene mutations of NPM1 were detected and typed by different-melting curve peak value of the probe through RT-PCR.@*RESULTS@#This method could detected the mutations of A, B, and D in NPM1 effectively with a sensitivity of 1%. Furthermore, 62 AML clinical samples were evaluated by the method. In the results, the detection rate and typing of NPM1 mutations were consistent with the sequencing results of clinical samples.@*CONCLUSION@#There are three features in the method of fluorescence melting curve analysis: stable PCR system, easy to operate, and the easily distinguishable results. The method might meet the demand for rapid typing of NPM1 gene mutation in early diagnosis or concomitant diagnosis of AML.
Subject(s)
Exons , Genotype , Humans , Leukemia, Myeloid, Acute/genetics , Mutation , Nuclear Proteins/geneticsABSTRACT
A boy was admitted on day 3 after birth due to shortness of breath for 2 days and cyanosis for 1 day. He had clinical manifestations of dyspnea in the early postnatal period and situs inversus, and was finally diagnosed with Kartagener syndrome. His condition was improved after oxygen therapy, anti-infective therapy, and aerosol therapy. The genetic testing showed that there was a large-fragment loss of heterozygosity, exon 48_50, and a hemizygous mutation, c.7915C > T(p.R2639X), in the
Subject(s)
China , Dyspnea , Exons , Humans , Infant, Newborn , Kartagener Syndrome/therapy , Male , Situs Inversus/geneticsABSTRACT
This is a case report on a 1-day-old male neonate admitted due to a weak cry for 1 day and recurrent circumoral cyanosis for 2 hours. He had unusual facial features at birth, with a single transverse palmar crease on both hands, flat feet, weak cry, feeding difficulties, congenital heart disease, and abnormality on cerebral MRI. Whole exome sequencing showed a
Subject(s)
Exons , Genetic Testing , Humans , Infant, Newborn , Intellectual Disability/genetics , Male , Mutation , Exome SequencingABSTRACT
OBJECTIVE@#To explore the genetic basis for a pedigree affected with hereditary multiple osteochondroma (HMO).@*METHODS@#Peripheral blood samples were collected from the proband and members of his pedigree with informed consent. Following extraction of genomic DNA, all coding exons and flanking intronic sequences (-10 bp) of the EXT1 and EXT2 genes were subjected to targeted capture and next generation sequencing (NGS). Suspected variant was verified by Sanger sequencing.@*RESULTS@#A heterozygous nonsense variant (c.1911C>A) was found in exon 10 of the EXT1 gene in the proband and his affected father but not in a healthy sister and normal controls. The variant was classified as a pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (PVS1+PM2+PP1). Bioinformatic analysis predicted that the c.1911C>A variant may be disease-causing via nonsense-mediated mRNA decay and anomalous splicing.@*CONCLUSION@#The c.1911C>A variant probably underlay the disease in this pedigree. Discovery of this variant enriched the variant spectrum of HMO.
Subject(s)
Codon, Nonsense , Exons/genetics , Exostoses, Multiple Hereditary/genetics , Heterozygote , Humans , PedigreeABSTRACT
OBJECTIVE@#To explore the genetic basis for a patient with primary ciliary dyskinesia (PCD).@*METHODS@#High-throughput sequencing and bioinformatic analysis were carried out to identify pathogenic variant in the patient. Suspected variant was verified by Sanger sequencing among the family members, and intracytoplasmic sperm injection (ICSI) was used to achieve the pregnancy.@*RESULTS@#The patient had obstructive azoospermia, measurement of nasal NO exhalation at 84 ppb, and typical symptoms of PCD in nasal sinuses and lungs. DNA sequencing showed that he had carried biallelic variants of the DNAH5 gene, namely c.1489C>T (p.Q497X) in exon 11 and c.6304C>T (p.R2102C) in exon 38. His wife achieved clinical pregnancy with the assistance of ICSI.@*CONCLUSION@#Above finding has enriched the spectrum of DNAH5 gene variants, though the latters did not affect the outcome of pregnancy by ICSI.