OBJECTIVE: To carry out genetic testing and clinical phenotypic characterization on a four-generation Chinese pedigree affected with Stickler syndrome type I and explore its genotype-phenotype correlation. METHODS: A child presented at the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine in February 2023 for micrognathia, glossoptosis and cleft palate and his family members were selected as the study subjects. Clinical data were collected from the affected members, and peripheral blood samples were obtained from 17 participants (including 4 patients and 13 asymptomatic individuals). Whole exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing. Genotype-phenotype correlation was analyzed by integrating the sequencing data with evidence from existing literature. This study has bee granted by the Ethics Committee of Guangdong Provincial Hospital of Traditional Chinese Medicine and Guangzhou Women and Children's Medical Center (Ethics No.: 2022-406B00). RESULTS: The four-generation pedigree has comprised 19 members. In addition to the proband, 5 affected individuals had manifested with high myopia, congenital cataracts, and progressive vision loss. Two deceased members reportedly exhibited similar ocular manifestations. Among the four living patients, two had developed retinal detachment, while two others presented with chronic joint pain onset between 35 ~ 40 years of age. One patient required hip replacement surgery at age 42 secondary to femoral head necrosis. The proband, the youngest affected member, exhibited characteristic phenotypes including congenital micrognathia and cleft palate, consistent with Pierre-Robin syndrome. Genetic analysis revealed a heterozygous nonsense mutation in COL2A1 (NM_001844.5: c.2668C>T; p.Gln890Ter) segregating with the disease in all four symptomatic patients. This variant was absent in asymptomatic family members and unaffected controls. While the mutation is listed in ClinVar, no clinical case report has associated it with this phenotypic spectrum. It was not recorded in population databases (gnomAD v4.1.0, 1000 Genomes Project, or ExAC), supporting its potential pathogenicity. CONCLUSION This study has diagnosed a four-generation Chinese pedigree with Stickler syndrome type I attributed to the pathogenic COL2A1 variant c.2668C>T (p.Gln890Ter), which is a rare nonsense mutation associated with ocular predominance and variable skeletal involvement. Notably, this family exhibited marked clinical heterogeneity despite sharing the identical genotype, which highlighted the challenges in phenotype-genotype correlation. The autosomal dominant transmission pattern observed in this pedigree has provided critical insights into COL2A1-related collagenopathies and underscored the necessity of ultrasonographic monitoring for ocular anomalies during prenatal diagnosis. Above findings have advanced our understanding of the pleiotropic effects in type Ⅱ collagen disorders and laid the foundation for precision-based genetic counseling, enabling targeted cascade screening and implementation of tertiary prevention strategies against congenital disabilities for high-risk families.
Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Arthritis/genetics* ; Collagen Type II/genetics* ; Connective Tissue Diseases/genetics* ; Exome Sequencing ; Genetic Association Studies ; Genotype ; Hearing Loss, Sensorineural/genetics* ; Mutation ; Pedigree ; Phenotype ; Retinal Detachment/genetics* ; East Asian People/genetics*

Objective To measure the dose to the primary operator and assistant operators by employing eight beam projections commonly used in coronary angiography with and without radiation protection shields in order to supply helpful guidance on radiation protection in cardiac intervention.Methods From 20 to 180 cm above the ground at the primary and assistant operators' locations,a DoseAware personal dose meter was placed in terms of an increment of 20 cm to measure radiation dose.Eight commonly used beam projections were performed,including LAO (left anterior oblique) 45°,RAO (right anterior oblique) 30°,CRAN (cranial)25°,cranial LAO (LAO45°/25°),caudal LAO(LAO45°/ 25°),CAUD (caudal) 25°,cranial RAO (RAO30°/25°),caudal RAO (caudal RAO30°/25°).Under the two different conditions,with or without radiation protection shields,the doses to the operators in the selected beam projections were respectively recorded at nine measuring positions and the shielding factor were calculated.Results The primary operator was effectively protected with radiation protection shields.In the standing area of the primary operator,except for the position at the height of 120 cm (radiation dose rate:0.35-4.78 mSv/h;shielding factor:27.67％-89.33％),the shielding factor for each measuring position was above 91％.Higher radiation doses were found at caudal LAO,LAO,and cranial LAO.The shielding factor for the assisting operator was lower than for the primary operator.In the standing area of the assisting operator (radiation dose rate:0.27-1.86 mSv/h;shielding factor:30.34％-92.13％),the peak levels were found at the height of 80,100,140 cm.And caudal RAO,caudal LAO,CRAN,LAO were found to have received higher radiation doses.Conclusions Emphasis should be attached to the use of radiation shields in coronary angiography.With radiation protection shields,higher dose is still recorded in caudal LAO,LAO,cranial LAO,caudal RAO.Furthermore,it should be paid more attention to radiation protection at 80-140 cm height,and less prolonged exposure should be employed in those beam projections mentioned above.

Objective To evaluate the radiation protective efficacy of different types and the positions of ceiling-suspended lead shield to the principal and assistant interventional operators in order to provide a scientific basis for the selection of optimal scheme in using ceiling-suspended lead shield.Methods At the principal and assistant interventional operators’ standing places the personal dose-measuring instruments were set up, which were placed at the height of 20 cm to 180 cm above the ground with an interval distance of 20 cm between each other.The postero-anterior (PA) projection and left lateral projection were used.The ceiling-suspended protection lead shields included lead glass (glass type) and lead glass with connected lead flexible stripe below (mixed type).The placed sites of the protection lead-shields were close to the principal operator, away from the principal operator, on the left side of the principal operator and close to the X-ray tube respectively.The radiation doses of PA projection and left lateral projection were determined.The real-time radiation dose rate and dose shielding rate at the nine measuring positions for the principal operator and assistant operator were separately calculated.The results were analyzed.Results The radiation protection of the glass type was slightly superior to that of the mixed type, but the difference was not significant.The principal operator was best protected when the shield was positioned close to him in the PA projection, and for left lateral projection the principal operator was best protected when the shield was positioned on his left side.For the assistant operator, the optimal protection was obtained when the shield was positioned close to him in both PA and left lateral projection.In the optimal position of ceiling-suspended lead shield, the highest radiation dose rate (0.71 mSv/h in glass group and 1.07 mSv/h in mixed group) was recorded on the principal operator at the height of 120 cm at PA projection, and higher radiation dose rate (≥0.47 mSv/h) was recorded on every point of both operators at the left lateral projection.Meanwhile, the overall received radiation doses of the two groups were very close.At the principal operator standing area, except for the position of 120 cm height (attenuation ratio 60.11% in glass group and 39.89% in mixed group), the attenuation ratio of each measuring point was above 93%.And the assistant operator standing area the attenuation ratio was 57%-97%.The lateral shielding ratio was generally slightly higher than PA shielding ratio.Conclusion The radiation protection effect of the two type shields is quite similar, both shields can obtain excellent protection efficacy.But the radiation dose at the height of 120 cm above the ground at PA projection is higher for the principal operator, while at lateral projection the radiation dose at all height levels is still relatively higher for both operators.Therefore, the radiation protection at the level of 120 cm height needs to be strengthened and the lateral projection exposure should be used as less as possible.