Clinical and genetic study of a child with delayed language development carrying ring 22 and a 22q13 microdeletion / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child featuring delayed language development.@*METHODS@#The patient was subjected to conventional G-banding chromosomal karyotyping and single nucleotide polymorphism microarray (SNP array) analysis.@*RESULTS@#The karyotype of the child was 46, XY, r(22)(p11.2q13). SNP array analysis has identified a hemizygous 1.67 Mb deletion at 22q13 (arr [Hg19]22q13.33 (49 531 302-51 197 766)×1).@*CONCLUSION@#The child has carried a ring 22 in addition with a 22q13 microdeletion. The results may provide clues for her condition and genetic counseling for the family.

Clinical and genetic analysis of a case with infantile Parkinsonism with motor delay due to tyrosine hydroxylase deficiency / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic variants in a child with tyrosine hydroxylase-deficient infantile Parkinsonism with motor delay.@*METHODS@#Clinical feature of the patient was summarized. Genomic DNA was extracted from peripheral blood samples taken from the child and her family members. All exons of GCH1, TH and SPR genes were subjected to targeted capture and next-generation sequencing. Suspected variants were verified by Sanger sequencing.@*RESULTS@#The child could not sit alone at 7 month and 11 days. Physical examination suggested motor retardation and hypotonia, limb stiffness, head nodding, slight torticollis, and language and intellectual developmental delays. She developed involuntary shaking of limbs at 3 month old, which lasted approximately 10 seconds and aggregated with excitement and before sleeping. Cranial MRI revealed widening of subarachnoid space on the temporomandibular and particularly temporal sides. Genetic testing revealed that she has carried a nonsense c.457C>T (p.R153X) variant, which was known to be pathogenic, and a novel missense c.720C>G (p.I240M) variant of the TH gene. The two variants were derived from her father and mother, respectively.@*CONCLUSION@#The child was diagnosed as tyrosine hydroxylase-deficient infantile Parkinsonism with motor delay due to compound heterozygous variants of the TH gene. Above finding has enriched the spectrum of TH gene variants.

Phenotypic and genetic analysis of a boy with partial trisomy of 22q / 中华医学遗传学杂志

OBJECTIVE@#To delineate the nature and origin of chromosomal aberration in a boy with mental retardation and multiple congenital deformities.@*METHODS@#Chromosomal karyotypes of the proband and his parents were determined by routine G-banding analysis. Genomic DNA was also analyzed with single nucleotide polymorphism array (SNP array).@*RESULTS@#The karyotype of the proband was 46,X,add(Y)(q11.23). No karyotypic abnormality was detected in either parent. SNP array has identified a de novo 21.6 Mb duplication at 22q12qter in the proband.@*CONCLUSION@#The de novo 22q12qter duplication probably underlies the abnormalities in the proband.

Phenotypic and genetic analysis of a boy with a 10p15.3 deletion and partial trisomy 18p syndrome / 中华医学遗传学杂志

OBJECTIVE@#To delineate the nature and origin of chromosomal aberration in a girl with mental retardation.@*METHODS@#Genomic DNA was analyzed by using single nucleotide polymorphism-based array (SNP array). The proband and her parents were subjected to routine G-banded chromosomal karyotyping analysis.@*RESULTS@#SNP array has identified a 1.2 Mb microdeletion at 10p15.3 and a duplication at 18p11.21-pter in the proband. The patient was also found to harbor a structural aberration involving 10p. The karyotype of her father was 46,XY,t(10;18)(p15;p11.2), while her mother was found to be normal.@*CONCLUSION@#The structural aberration of 10p carried by the patient has derived from her father whom has carried a balanced translocation of t(10;18). Her karyotype was finally determined as 46,XX,der(10)t(10;18)(p15;p11.2)pat. The abnormal phenotype of the patient can probably be attributed to the presence of 10p15.3 microdeletion and 18p11.21-pter duplication.

Clinical characteristics and genetic analysis of primary coenzyme Q10 deficiency caused by COQ4 gene mutation / 中华内分泌代谢杂志

Objective@#To explore the clinical and genetic characteristics of primary coenzyme Q10 deficiency caused by coenzyme Q4 (COQ4) variants.@*Methods@#Clinical data were collected, while COQ4 gene was sequenced.@*Results@#Here were reported a boy of 3 months old who came to our hospital presented with feeding difficulties, repeated respiratory infections, convulsions for 3 months. He was subsequently diagnosed as cerebral atrophy, and growth retardation. All exons were sequenced.c.211G>A(p.A71T, maternal), c. 436T>A(p.F146I, paternal) were detected. After treatment with coenzyme Q10, the convulsive symptoms improved significantly. Literature review revealed that totally 14 cases with primary coenzyme Q10 deficiency caused by COQ4 gene mutation were reported. The onset age varies from neonatal to 18 years old, and the clinical manifestations are heterogeneous, including cardiomyopathy, epilepsy, ataxia, cerebellar atrophy, respiratory insufficiency, and growth retardation.@*Conclusion@#For cases with atypical clinical manifestations of primary coenzyme Q10 deficiency, gene detection is helpful for an early diagnosis and treatment.

Clinical and genetic diagnosis of a pedigree affected with autosomal recessive Alport syndrome / 中华医学遗传学杂志

Objective@#To explore the genetic basis of a child with chronic kidney disease featuring renal shrinkage and creatinine increase.@*Methods@#Peripheral venous blood samples were taken from the child, his brother and two parents and subjected to whole exome sequencing. Suspected mutations were verified by Sanger sequencing. Bioinformatic analysis was carried out to predict the influence of mutations on the structure and function of the protein product.@*Results@#High-throughput and Sanger sequencing revealed that the child has carried compound heterozygous mutations of the COL4A4 gene, namely c. 4550T>G in exon 47 (inherited from his mother) and c. 199C>T in exon 5 (inherited from his father). Neither mutation was reported previously. Bioinformatic analysis showed that both mutations have located in highly conserved regions. The same mutations were not found in his brother.@*Conclusion@#The compound heterozygous c. 4550T>G and c. 199C>T mutations probably underlie the disease in this child. The findings have enriched the mutation spectrum of the COL4A4 gene.

Clinical and genetic diagnosis of a pedigree affected with autosomal recessive Alport syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis of a child with chronic kidney disease featuring renal shrinkage and creatinine increase.@*METHODS@#Peripheral venous blood samples were taken from the child, his brother and two parents and subjected to whole exome sequencing. Suspected mutations were verified by Sanger sequencing. Bioinformatic analysis was carried out to predict the influence of mutations on the structure and function of the protein product.@*RESULTS@#High-throughput and Sanger sequencing revealed that the child has carried compound heterozygous mutations of the COL4A4 gene, namely c.4550T>G in exon 47 (inherited from his mother) and c.199C>T in exon 5 (inherited from his father). Neither mutation was reported previously. Bioinformatic analysis showed that both mutations have located in highly conserved regions. The same mutations were not found in his brother.@*CONCLUSION@#The compound heterozygous c.4550T>G and c.199C>T mutations probably underlie the disease in this child. The findings have enriched the mutation spectrum of the COL4A4 gene.

Morphology and pathogenesis of 47, XYY/47, XY, +mar identified in patients with super male syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the source and morphology of supernumerary markers from patients with 47,XYY/47,XY, +mar and supermale syndrome.</p><p><b>METHODS</b>Conventional GTG banded karyotyping and dual-color fluorescence in situ hybridization (FISH) were performed on 21 such patients.</p><p><b>RESULTS</b>Among these cases, 18 had their small supernumerary marker derived from the Y chromosome. Three were derived from autosomal chromosomes. Those derived from Y chromosome were small fragments with centromeres, while those derived from autosomes were in the ring form.</p><p><b>CONCLUSION</b>In children with supermale syndrome and 47,XYY/47,XY,+ mar, the supernumerary marker chromosomes primarily derive from sex chromosomes. These small chromosomes mainly have the forms of small segments with centromeres or rings. For such children, molecular cytogenetic analysis can facilitate genetic counseling and prenatal diagnosis.</p>

Identification of a novel splicing mutation in COL1A1 gene in a Chinese family affected with typeⅠosteogenesis imperfecta / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the genetic cause for a large family affected with typeⅠosteogenesis imperfecta.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral venous blood samples. The entire coding region and intron-exon boundaries of the COL1A1 gene were subjected to PCR amplification and direct sequencing. Total RNA was also extracted from immortalized B cell lines from the patients, with the first strand of cDNA synthesized with an oligo(dT)18 primer. The PCR products were directly sequenced using the TA cloned plasmid.</p><p><b>RESULTS</b>A c.3208G>A mutation has been identified in the COL1A1 gene, which can alter the splicing pattern of mRNA.</p><p><b>CONCLUSION</b>A novel splicing mutation c.3208G>A of the COL1A1 gene probably underlies the disease.</p>