OBJECTIVE: To carry out genetic testing on two fetuses with prenatal ultrasound finding of polydactyly and renal abnormalities to determine the underlying causes. METHODS: Two fetuses with structural abnormalities detected by prenatal ultrasound at Cangzhou People's Hospital in 2021 were selected as the study subjects. Genomic DNA was extracted from the muscle tissue of the abortus and peripheral blood samples from both parents. Whole-exome sequencing (WES) was conducted on the trio to detect the genetic variants. Quantitative PCR was used to validate the exonic deletions. This study has been approved by the Ethics Committee of Cangzhou People's Hospital (Ethics No.K2020-049). RESULTS: Prenatal ultrasound revealed postaxial polydactylies of fingers and toes and slightly enlarged kidneys with increased echogenicity in fetus 1, along with polydactyly of both hands, enlarged kidneys, and enhanced echogenicity of renal parenchyma in fetus 2. Trio-WES analysis revealed that fetus 1 has harbored a pathogenic c.1339G>A variant of the BBS1 gene, along with a heterozygous 426 bp deletion in the 11q13.2 region, which was unreported previously. The deletion has involved exons 10 and 11 of the BBS1 gene. The two variants were inherited from its mother and father, respectively. Fetus 2 was found to harbor a pathogenic c.539G>A variant and a likely pathogenic c.49G>A variant of the BBS10 gene, which were inherited from its mother and father, respectively. The c.49G>A variant has not been documented in databases and the literature. CONCLUSION Two rare fetuses with Bardet-Biedl syndrome have been diagnosed. Above finding has expanded the mutational spectrum of this syndrome and has important implications for genetic counseling for the affected families.
Humans ; Bardet-Biedl Syndrome/diagnostic imaging* ; Female ; Pregnancy ; Fetus/abnormalities* ; Ultrasonography, Prenatal ; Phenotype ; Polydactyly/diagnostic imaging* ; Exome Sequencing ; Adult ; Genetic Testing ; Male ; Prenatal Diagnosis ; Group II Chaperonins/genetics* ; Microtubule-Associated Proteins

OBJECTIVE: To analyze the clinical characteristics of a patient with Short rib-polydactyly syndrome type 6 (SRTD6) with long-term misdiagnosis, and improve its clinical recognition by reviewing the relevant literature. METHODS: A patient presented at the Children's Hospital Affiliated to Zhejiang University School of Medicine on August 19, 2024 for the discovery of liver dysfunction for 13 years and vision loss for 9 years was selected as the study subject. Her medical history, clinical data, laboratory findings and results of imaging examination were collected. High-throughput sequencing was carried out, and candidate variants were verified by Sanger sequencing. This study was approved by the Ethics Committee of the Hospital (Ethics No.: 2021-IRB-292). RESULTS: The patient had long-term unexplained liver dysfunction, vision loss, and growth delay. Blood acylcarnitine and urinary organic acid analysis have failed to found any abnormality. Previous genetic testing revealed a homozygous c.203A>C (p.Glu68Ala) missense variant in the ETFDH gene, leading to a misdiagnosis of various acyl-CoA dehydrogenase deficiencies. However, treatment with high-dose vitamin B₂ showed a poor effect. Physical examination revealed small hands, short and stubby fingers, and a narrow chest. Medical imaging showed shortened bilateral ribs, a narrowed chest, and short, thick metacarpals. High-throughput sequencing has detected a pathogenic homozygous c.1957C>T (p.R653*) nonsense variant in the NEK1 gene, confirming the diagnosis of SRTD6. CONCLUSION SRTD6 is characterized by rib and sternum dysplasia as the primary skeletal deformities, which is often accompanied by multi-organ impairment. Genetic testing can facilitate the precise diagnosis.
Humans ; Female ; Diagnostic Errors ; Short Rib-Polydactyly Syndrome/diagnosis* ; High-Throughput Nucleotide Sequencing

OBJECTIVE: To explore the prenatal features and genetic etiology of a fetus with Short-rib cage dysplasia (SRTD) due to variants of DYNC2H1 gene. METHODS: A pregnant women presented at Xinxiang Central Hospital in June 2020 for abnormal prenatal ultrasound findings was selected as the study subject. With informed consent obtained, amniotic fluid sample was extracted from the woman, and clinical data of the fetus were collected. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of Xinxiang Central Hospital [Ethics No.: 2025-214-01(K)]. RESULTS: At 25⁺⁶ weeks gestation, genetic testing revealed that the fetus has harbored compound heterozygous variants of the DYNC2H1 gene, namely c.10585C>T (p.Arg3529Ter) and c.8954T>G (p.Val2985Gly), which were derived from its father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.10585C>T (p.Arg3529Ter) and c.8954T>G (p.Val2985Gly) variants were classified as pathogenic (PVS1+PM2_supporting+PM3+PP5) and likely pathogenic (PM1+PM2_supporting+PM3+PP3), respectively. Bioinformatics analysis suggested that both variants may affect the 3D structure of the DYNC2H1 protein. CONCLUSION The compound heterozygous variants of c.10585C>T (p.Arg3529Ter) and c.8954T>G (p.Val2985Gly) of the DYNC2H1 gene probably underlay the pathogenesis of SRTD in the fetus. Above findings had facilitated prenatal diagnosis and genetic counseling for the couple.
Humans ; Female ; Pregnancy ; Cytoplasmic Dyneins/chemistry* ; Prenatal Diagnosis ; Adult ; Short Rib-Polydactyly Syndrome/diagnostic imaging* ; Mutation ; Exome Sequencing ; Fetus/abnormalities* ; Ultrasonography, Prenatal

OBJECTIVE: To explore the clinical and genetic characteristics of a child with Pallister-Hall syndrome (PHS). METHODS: DNA was extracted from peripheral blood sample from the child and subjected to whole exome sequencing. Suspected variants were verified by Sanger sequencing of his family members. RESULTS: Genetic testing revealed that the child has harbored a heterozygous c.3320_3330delGGTACGAGCAG (p.G1107Afs×18) variant of the GLI3 gene. Neither parent was found to carry the same variant. CONCLUSION The c.3320_3330delGGTACGAGCAG (p.G1107Afs×18) frameshift variant of the GLI3 gene probably underlay the pathogenesis of PHS in this child. Genetic testing should be considered for patients featuring hypothalamic hamartoma and central polydactyly.
Humans ; Child ; Pallister-Hall Syndrome/genetics* ; Kruppel-Like Transcription Factors/genetics* ; Zinc Finger Protein Gli3/genetics* ; Polydactyly/genetics* ; Hamartoma/pathology* ; Nerve Tissue Proteins/genetics*

OBJECTIVE: To explore the genetic basis for a child featuring short stature and postaxial polydactyly. METHODS: A child who presented at Ningbo Women & Children's Hospital in May 2021 due to the"discovery of growth retardation for more than two years" was selected as the subject. Peripheral blood samples of the child and his parents were collected for the extraction of genomic DNA. Whole exome sequencing was carried out for the child, and candidate variant was verified by Sanger sequencing of his family members. RESULTS: The child was found to harbor a heterozygous c.3670C>T (p.Q1224) variant of the GLI2 gene, which may lead to premature termination of protein translation. The variant was not detected in either parent. CONCLUSION The child was diagnosed with Culler-Jones syndrome. The c.3670C>T (p.Q1224*) variant of the GLI2 gene probably underlay the disease in this child.
Child ; Female ; Humans ; Fingers ; Mutation ; Nuclear Proteins/genetics* ; Polydactyly/genetics* ; Toes ; Zinc Finger Protein Gli2/genetics*

OBJECTIVE: To report on the clinical characteristics of a family of short-rib polydactyly syndrome type III and its pathogenic variants. METHODS: Muscle samples from the the third fetus was collected after the induction of labor, and peripheral blood samples of its parents and grandparents were also collected. Whole exome sequencing (WES) was carried out for the pedigree. Candidate variants were verified by Sanger sequencing of the family. RESULTS: The proband was found to harbor a c.9819+1G>A variant and a c.4625C>A variant of the DYNC2H1 gene, which were respectively inherited from its mother and father. Sanger sequencing verified that the family has fit the autosomal recessive inheritance. CONCLUSION The c.9819+1G>A and c.4625C>A variants of the DYNC2H1 gene probably underlay the short-rib polydactyly syndrome type 3 in the proband.
Child ; Cytoplasmic Dyneins/genetics* ; Humans ; Mutation ; Pedigree ; Ribs ; Short Rib-Polydactyly Syndrome/genetics*

OBJECTIVE: To analyze the pathogenic variant of preaxial polydactyly in a Chinese Han pedigree and identify the cause of polydactyly. METHODS: The peripheral blood DNA of the proband and her parents was extracted. The polydactyly-related genes were detected by trio whole exome sequencing, and the suspected pathogenic gene was screened out. Sanger sequencing was applied to other members of the pedigree. RESULTS: The results of gene sequencing showed that the LMBR1 gene had a heterozygous variant of c.423+4909(IVS5)C>T in 6 patients of the pedigree. The same variant was not detected in family members with normal phenotype. Based on the ACMG guidelines, c.423+4909(IVS5)C>T of the LMBR1 gene was predicted to be pathogenic (PM1+PM2+PP1-S(PS)+PP4+PP5). CONCLUSION The heterozygous C>T variant at position 4909 of intron 5 of the LMBR1 gene probably underlies the disease in this pedigree.
China ; Female ; Humans ; Mutation ; Pedigree ; Polydactyly/genetics* ; Thumb ; Whole Exome Sequencing

OBJECTIVE: To detect potential mutation in a Chinese pedigree affected with congenital limb malformations. METHODS: Clinical data was collected. Genomic DNA was extracted from peripheral blood samples of family members. The zone of polarizing activity regulatory sequence (ZRS) were amplified by PCR and subjected to direct sequencing. RESULTS: Among the 13 individuals in this pedigree, there were 4 PPD patients, who were characterized by varying degrees of deformity. The female patients suffered triphalangeal thumb and preaxial polydactyly, while the male patients only had preaxial polydactyly. Only one patient had foot involvement. TA heterogeneous mutations was discovered in the ZRS (105C>G) in all patients, the same mutation was not detected in 2 healthy family members. CONCLUSION The inheritance pattern of PPD was autosomal dominant inheritance. There was a significant variability of symptoms among family patients. The heterozygous mutation of the ZRS (105C>G) probably underlie the disease.
Female ; Genetic Testing ; Hand Deformities, Congenital ; genetics ; Humans ; Limb Deformities, Congenital ; genetics ; Male ; Membrane Proteins ; genetics ; Pedigree ; Polydactyly ; genetics ; Thumb ; pathology

OBJECTIVE: To detect potential mutation in a large pedigree affected with preaxial polydactyly II. METHODS: With informed consent obtained, peripheral blood samples were collected from the proband, her family members as well as 100 healthy controls. Genomic DNA was extracted. The zone of polarizing activity regulatory sequence (ZRS) of the SHH gene was amplified by PCR and subjected to bi-directional Sanger sequencing. RESULTS: The pedigree had typical preaxial polydactyly II. A heterozygous C>G mutation at position 105 of the ZRS region was detected in all patients but none of the unaffected members and 100 healthy controls. CONCLUSION The heterozygous 105C>G mutation of the ZRS region probably underlies the disease in this pedigree.
DNA Mutational Analysis ; Female ; Humans ; Mutation ; Pedigree ; Polydactyly ; Thumb

INTRODUCTION: Polydactyly of the foot is not uncommon, with the preaxial type or hallux duplication comprising 15% of cases.2 Metatarsal type preaxial polydactyly (MTPP) accounts for an estimated third of all reported preaxial polydactyly cases. Traditional surgical procedures for this condition frequently have drawbacks that include varying degrees of hallux varus and a bigger forefoot.1 Due to these disadvantages, developed a simple and effective technique for the reconstruction of MTPP. CASE REPORT: Amalgamating osteotomy procedures were done for bilateral MTPP in an 18-month old girl who had been experiencing shoe ware difficulty. An excellent and pain-free functional outcome was achieved with good cosmetic appearance and an improved ability to wear various kinds of footwear. CONCLUSION Amalgamating osteotomy could be the procedure of choice for the reconstruction of metatarsal type preaxial polydactyly. Case series and long-term follow-ups should be done to compare outcomes with other surgical techniques.
Polydactyly