Clinical and molecular genetic analysis of a patient with 3-M syndrome / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical features and molecular genetic etiology of a patient with 3-M (Miller McKusick Malvaux) syndrome from a consanguineous parentage family, and to explore the relationship between genotype and phenotype.@*METHODS@#After the consent of the proband's guardian and the informed consent form was signed, DNA was extracted from peripheral blood samples of the proband and her parents for chromosome microarray analysis, medical exome sequencing and parental verification.@*RESULTS@#A total of 247.1 Mb loss of heterozygosity was found in the proband with a CytoScan 750K array. Furthermore, a homozygous variant (c.458dupG) of the OBSL1 gene was found using high-throughput sequencing, which was inherited from her parents. Based on the criteria and guidelines of genetic variation of American College of Medical Genetics and Genomics, the variant is predicted to be pathogenic (PVS1+PM2+PP4), and only one case was reported previously.@*CONCLUSION@#Spina bifida occulta and lower eyelid fat pad may be a special phenotype of c.458dupG variant of the OBSL1 gene. Our study may provide a useful reference for evaluating the relationship between genotype and phenotype of 3-M syndrome type 2.

Genetic analysis of a Chinese pedigree affected with congenital split-hand/foot malformation / 中华医学遗传学杂志

OBJECTIVE@#To analyze the molecular genetics of a Chinese pedigree with congenital hand foot cleft.@*METHODS@#Single nucleotide polymorphism microarray (SNP array) was used to analyze the whole genome copy number variation.@*RESULTS@#SNP array analysis showed that there was a 433 kb repeat in 10q24.31-10q24.32 region, which contained LBX1, BTRC, POLL, OPCD and FBXW4 genes.@*CONCLUSION@#Microduplication of chromosome 10q24.31-10q24.32 may be the cause of congenital hand foot cleft in this pedigree.

Clinical and genetic analysis of a patient with 17-hydroxylase/17,20-lyase deficiency / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of a patient with 17-hydroxylase/17,20-lyase deficiency.@*METHODS@#The patient was infertile without contraception. Laboratory examination showed her chromosomal karyotype to be 46, XX. DNA sequencing was performed to detect variants of CYP17A1 gene in the patient and her family members.@*RESULTS@#Sanger sequencing revealed that the patient has carried homozygous variant c.1486C>T in the exon 8 of the CYP17A1 gene, which resulted in substitution of arginine by cysteine (p.Arg496Cys). Her family members were all heterozygotes for the same variant.@*CONCLUSION@#Homozygous variant of the CYP17A1 gene c.1486C>T probably underlay the 17-hydroxylase deficiency in this patient. Above finding has enabled accurate genetic counseling and prenatal diagnosis for her family.

Analysis of a pedigree with partial trisomy 9 and partial monosomy 13 derived from a maternal balanced t(9;13) translocation / 中华医学遗传学杂志

OBJECTIVE@#To determine the nature and origin of aberrant chromosomes in a child with multiple anomalies and psychomotor retardation.@*METHODS@#Routine G-banding was carried out to analyze the karyotypes of the patient and his parents, and next generation sequencing for copy number variations (CNV-seq) was used for the fine mapping of the aberrant chromosomal regions.@*RESULTS@#The proband and his uncle exhibited psychomotor retardation, craniofacial malformation, infantile external genitalia, and concealed penis. Cytogenetic analysis indicated that the child has a 46,XYqh+,+(9),t(9;13)(q13;q12),pat,-13 karyotype. His uncle was XYqh+,+(9),t(9;13)(q13;q12)mat,-13, his father was 46,XYqh+,t(9;13)(q13;q12)mat, his grandmother was 46,XX,t(9;13)(q13;q12), and his grandfather was 46,XYqh+. The result of CNV-seq assay for the child was 46,XY,+9p(pter-p13.2,-40 Mb×3). No deletion was detected.@*CONCLUSION@#The partial trisomy 9 and partial monosomy 13 probably underlie the phenotypic abnormalities in the child. Combined chromosomal karyotyping and DNA sequencing can facilitate delineation of the nature and origin of the aberrant chromosomes.

Analysis of FGFR2 gene mutations in two Chinese families with Crouzon syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect potential mutations of fibroblast growth factor receptor 2 gene (FGFR2) in two Chinese families with Crouzon syndrome.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood leukocytes of 20 members from two affected families. All of the 18 exons of the FGFR2 gene were amplified with polymerase chain reaction and sequenced after purification.</p><p><b>RESULTS</b>A missense mutation c.868T>C (p.W290R) in exon 8 of the FGFR2 gene was found solely in 2 affected members from family 1. Another missense mutation c.833G>T (p.C278F) in exon 8 was found solely in 5 affected members of family 2.</p><p><b>CONCLUSION</b>The missense mutations of the FGFR2 gene are responsible for the Crouzon syndrome in the two families. The c.868T>C missense mutation is reported for the first time in Chinese population.</p>