Humans ; Consanguinity ; Exome Sequencing ; Mutation/genetics* ; Sequence Analysis, DNA ; Ciliary Motility Disorders ; Axonemal Dyneins/genetics*

OBJECTIVE: To explore the clinical characteristics and genetic basis of a child with Kartagener syndrome (KTS). METHODS: Trio-whole exome sequencing was carried out for the child and his parents, and candidate variants were verified by Sanger sequencing. Changes in protein structure due to missense variants were simulated and analyzed, and the Human Splicing Finder 3.0 (HSF 3.0) online platform was used to predict the effect of the variant of the non-coding region. RESULTS: The child had featured bronchiectasis, sinusitis and visceral inversion. Genetic testing revealed that he has harbored compound heterozygous variants of the DNAH5 gene, namely c.5174T>C and c.7610-3T>G. Sanger sequencing confirmed the existence of the variants. The variants were not found in the dbSNP, 1000 Genomes, ExAC, ClinVar and HGMD databases. Protein structural analysis suggested that the c.5174T>C (p.Leu1725Pro) variant may affect the stability of local structure and its biological activity. The results of HSF 3.0 analysis suggested that the c.7610-3T>G variant has probably destroyed a splicing receptor to affect the transcription process. CONCLUSION The compound heterozygous variants of the DNAH5 gene probably underlay the pathogenesis in the child. Above finding may facilitate the understanding of the clinical characteristics and genetic basis of KTS, and further expand the spectrum of DNAH5 gene variants.
Male ; Humans ; Child ; Mutation ; Kartagener Syndrome/genetics* ; Genetic Testing ; Mutation, Missense ; Exome Sequencing ; Axonemal Dyneins/genetics*

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.
Axonemal Dyneins/genetics* ; Exons ; High-Throughput Nucleotide Sequencing ; Humans ; Kartagener Syndrome/genetics* ; Male ; Sequence Analysis, DNA ; Sperm Injections, Intracytoplasmic

OBJECTIVETo investigate the clinical features, diagnosis and treatment of primary ciliary dyskinesia (PCD).

METHODSThree cases of PCD received endoscopic sinus surgery and were followed up for life quality and recovery. Among these 3 cases, two were twin brothers and the other girl was twin born with a healthy brother. The mucosa of inferior turbinate was extracted prior to the operation without narcotic and decongestant. The ultrastructure of mucosal cilia was detected with electron microscope. Nine exons of gene DNAH5 and chromosome in one case and her fraternal twin were evaluated.

RESULTSNasal and sinus CT imaging of the 3 cases showed chronic pansinusitis (1 case accompanied with situs inversus according with the diagnosis of Kartagener syndrome). The nasal polyp was resected, and the sinuses were opened. The twin brothers received the adenoidectomy. All patients felt nasal ventilation improved while the surgical field still covered with thick discharges during follow-up for 2 - 4 years. Ciliary ultrastructures of the three cases showed lateral dynein absent, the sequence of 9 exons of DNAH5 and chromosome presented no change in the fraternal twins.

CONCLUSIONSSurgery could improve the symptoms of sinusitis in PCD. Change of ciliary ultrastructure was an important indication of its pathological changes and molecular biology evaluation needs further study.

Axonemal Dyneins ; metabolism ; Child ; Cilia ; ultrastructure ; Exons ; Female ; Humans ; Kartagener Syndrome ; diagnosis ; genetics ; pathology ; Male ; Sinusitis ; diagnosis ; etiology ; genetics ; Young Adult

OBJECTIVETo analyze the clinical characteristics of primary ciliary dyskinesia(PCD) so as to improve the diagnostic level of this rarely seen disease.

METHODSTen patients with PCD were retrospectively reviewed, the medical history, symptoms, signs, lung CT or chest X-ray, rhino-sinus CT scan, nasal nitric oxide (NO) levels, nasal ciliary ultrastructure, DNAH5 and DNAH11 genetic mutation, as well as treatment outcome were analyzed.

RESULTSAll 10 patients had recurrent chronic sinusitis, otitis media, bronchitis/bronchiectasis since childhood. Nine cases with translocation of heart and big vessels were diagnosed as Kartagener syndrome. One woman was suffering from barrenness and one man sterility after marriage for long time without birth control. Nasal NO levels were significantly lower in 2 patients with PCD but it was almost normal in one patient. Ciliary ultrastructure investigated by transmission electron microscope were almost normal in 4 cases without missing of inner or outer dynein arms. Two cases taking exome capture sequencing showed that mutations happened in DNAH5 and DNAH11. Five subjects underwenting sanger sequencing on 6 common exon fragments of DNAH5 and DNAH11 did not show any abnormality. Ten cases took medication therapy, while 5 patients once underwent functional endoscope sinus surgery. All of the 10 patients had improvement of their symptoms and signs after treatment.

CONCLUSIONSThe PCD is so rare in clinic that it is easily misdiagnosed. Clinical characteristics, nasal NO levels, ciliary ultrastructure and genetic testing are significant for clinical diagnosis.

Adult ; Axonemal Dyneins ; genetics ; Child ; Cilia ; ultrastructure ; DNA Mutational Analysis ; Female ; Humans ; Kartagener Syndrome ; diagnosis ; genetics ; pathology ; Male ; Middle Aged ; Nasal Cavity ; chemistry ; Nitric Oxide ; analysis ; Retrospective Studies

Genetic susceptibility is involved in the pathogenesis of vitiligo. Association studies with a whole genome-based approach instead of a single or a few candidate genes may be useful for discovering new susceptible genes. Although the etiology of non-segmental and segmental types is different, the association between gene polymorphisms and vitiligo has been reported, without defining types or in non-segmental type. Whole genome-based single nucleotide polymorphisms (SNPs) were examined in patients with non-segmental and segmental types of vitiligo using the Affymetrix GeneChip 500K mapping array, and 10 functional classes of significant SNPs were selected. Genotyping and data analysis of selected 10 SNPs was performed using real-time PCR. Genotype and allele frequencies were significantly different between both types of vitiligo and three of the target SNPs, DNAH5 (rs2277046), STRN3 (rs2273171), and KIAA1005 (rs3213758). A stronger association was suggested between the mutation in KIAA1005 (rs3213758) and the segmental type compared to the non-segmental type of vitiligo. DNAH5 (rs2277046), STRN3 (rs2273171), and KIAA1005 (rs3213758) may be new vitiligo-related SNPs in Korean patients, either non-segmental or segmental type.
Adaptor Proteins, Signal Transducing/*genetics ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group/*genetics ; Autoantigens/*genetics ; Axonemal Dyneins/*genetics ; Calmodulin-Binding Proteins/*genetics ; Child ; Child, Preschool ; Female ; Gene Frequency ; *Genome, Human ; Genome-Wide Association Study ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Republic of Korea ; Vitiligo/*genetics ; Young Adult