中华医学遗传学杂志最新文献

Objective: To explore the clinical and genetic characteristics of a boy with X-linked familial Behcet-like autoinflammatory syndrome-2 (AIFBL2).

Methods: A boy who was admitted to Children's Hospital Affiliated to Zhengzhou University in December 2023 due to recurrent oral ulcers for 2 years, intermittent abdominal pain and fever for more than 1 year was selected as the study subject. Clinical data of the patient was collected. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. A literature search was conducted in OMIM, PubMed, Wanfang Data Knowledge Service Platform, China Biomedical Literature Service System, and the VIP database using the keywords "ELF4 gene" "deficiency in ELF4, X-linked" "ELF4 deficiency" and "DEX" to identify recently published studies. This study was approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No.: 2023-H-K44).

Results: The patient, a 12-year-old male, presented with recurrent mouth ulcers, fever and abdominal pain. Lymphocyte subsets showed a significant decrease in NK cells. Abdominal CT showed thickening of local intestinal wall in the lower right abdomen. Colonoscopy revealed a solitary deep longitudinal ulcer in the ileocecal region. Genetic testing revealed a hemizygote missense variant c.687C>G, with his mother showing the same mutation at this locus. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), the variant was considered likely pathogenic (PP1+PP2+PM2_Supporting+PP3+PP4). Literature review has found 19 AIFBL2 patients including 1 patient from this study. Mouth ulcer, fever, rash and abdominal pain were the primary clinical manifestations, for which genetic testing is the main diagnostic method.

Conclusion: The hemizygote c.687C>G missense variant of the ELF4 gene probably underlay the AIFBL2 in this child, which has provided a basis for his clinical diagnosis and genetic counseling.

The SMPX (small muscle protein X-linked) gene encodes a small-molecular-weight protein that is mainly expressed in skeletal and cardiac muscles and is involved in cytoskeletal dynamics and mechanical stress responses. In recent years, missense variants of the SMPX gene have been identified as the cause of a novel X-linked distal myopathy (Distal myopathy 7). This article has systematically reviewed the molecular functions, variant types, and pathological mechanisms of the SMPX gene by integrating its clinical classification, molecular pathological evidence, and experimental model data, and revealed its pathgenetic mechanism through protein aggregation, dynamic dysregulation of stress granules, abnormal Rac1/p38 signaling pathways, and future research directions.

Macrodactyly is a congenital malformation characterized by overgrowth of soft tissues and bones in limbs. Pathological adipose infiltration is the most common manifestation, often involving the median nerve and digital nerves, and may progress aggressively. At the same time, some patients may show abnormal bone hyperplasia, causing the fingers to deviate and limiting joint mobility. Although surgery can reduce the symptoms of the affected limb to a certain extent, the recurrence rate is high, often leading to the serious consequence of amputation. It has been confirmed that the occurrence of macrodactyly is closely related to gain-of-function mutation of PIK3CA and belongs to the "PIK3CA-related overgrowth spectrum". Targeted regulation of the PI3K/AKT/mTOR pathway is becoming an important treatment method. To enhance the understanding of this disease, promote the establishment of a precise diagnosis and treatment system for macrodactyly, and improve the prognosis of the disease, the Hand Plastic Surgery Committee of the Aesthetic and Plastic Surgeon Branch of Chinese Medical Doctor Association, Clinical Genetics Group of Medical Geneticist Branch of Chinese Medical Doctor Association, the Pediatric Plastic Surgery Group of Plastic Surgery Branch of Chinese Medical Association, and the Assistive Devices Application Committee of Chinese Rehabilitation Medicine Association have convened experts from well-known medical colleges and their affiliated hospitals across China to formulate this consensus, with an aim to promote in-depth research, precise diagnosis and treatment, and rehabilitation of macrodactyly.

Syndactyly is one of the most common congenital malformations of the hand/foot, characterized by varying degrees of soft tissue and/or skeletal fusion between adjacent fingers or toes. It may also occur alongside polydactyly, camptodactyly, brachydactyly, or congenital joint fusion. The heterogeneity in its clinical phenotypes and incomplete penetrance makes it challenging to establish clear diagnostic and treatment protocols/procedures. Conventionally, the management of syndactyly has mainly relied on clinical experience, with limited reference to cutting-edge genetic research and systematic treatment strategies. To standardize the diagnosis and treatment of syndactyly and update the treatment protocols, a consensus has been developed by experts from the Hand Plastic Surgery Committee of the Aesthetic and Plastic Surgeon Branch of Chinese Medical Doctor Association, Clinical Genetics Group of the Medical Geneticist Branch of Chinese Medical Doctor Association, Pediatric Plastic Surgery Group of Plastic Surgery Branch of Chinese Medical Association, and Assistive Devices Application Committee of the Chinese Rehabilitation Medicine Association, and leading universities and hospitals across China. This expert consensus, incorporating both clinical and genetic research, as well as recent international and domestic findings, aims to serve as a reference for clinicians.

Objective: To assess the impact of vanishing twin syndrome (VTS) on the accuracy of non-invasive prenatal testing (NIPT).

Methods: Three pregnant women who underwent NIPT testing at Guangdong Women and Children's from November 2019 to February 2020 were selected as the study subjects. The three women had either vanish twin syndrome or had undergone fetal reduction for other reasons in one of their twins, and were subsequently subject to NIPT, chromosome karyotyping, chromosome microarray analysis (CMA), and short tandem repeat (STR) analysis. This study has been approved by the Medical Ethics Committee of Guangdong Maternal and Child Health Hospital (Ethics No.: 20230132).

Results: Case 1 underwent selective fetal reduction at 8⁺ weeks of gestation. At 17⁺ weeks, NIPT showed a fetal DNA fraction of 2.806%, with results indicating the presence of Y chromosome and abnormal sex chromosome ratios. However, the women had subsequent uncomplicated vaginal delivery of a female infant, and no abnormality noted. Case 2 experienced spontaneous demise of one twin at 13 weeks' gestation. At 19 weeks, NIPT indicated a high risk for chromosome 21 (Z-score 4.671) in the surviving fetus, but subsequent evaluation showed no abnormality. Case 3, a dichorionic diamniotic (DCDA) twin pregnancy, underwent selective reduction at 13⁺ weeks due to fetal abnormalities in one twin. At 22⁺ weeks, NIPT for the surviving fetus indicated a high risk for chromosome 21 (Z-score 17.549), but subsequent evaluation was unremarkable.

Conclusion: In twin pregnancies, the relatively low cell-free fetal DNA (cffDNA) concentration can compromise the success rate and accuracy of NIPT compared to singleton pregnancies. Residual DNA from the demised fetus may persist for weeks following VTS or selective reduction, potentially causing false-positive NIPT results and interfering with sex chromosome prediction for the surviving fetus. Additionally, determining chorionicity is critical for reliable interpretation of NIPT results in twin pregnancies.

Talocalcaneal coalition is one of the most common tarsal coalitions caused by bone, cartilage or fibrous connection between the talus and calcaneus due to congenital factors. Many patients have no obvious symptoms, and the onset is mostly manifested by bony protrusions of the medial malleolus, pain when walking, and impaired mobility of the subtalar joint. Missed diagnosis and inappropriate treatment often occurred for its low incidence and insidious onset. Therefore, the Foot and Ankle Group of Orthopedics Branch of Chinese Medical Association, Professional Committee for Foot and Ankle Surgery of the Orthopedics Branch of Chinese Medical Doctor Association, Clinical Genetics Group of the Medical Geneticist Branch of Chinese Medical Doctor Association, Group of Genetic Disease Prevention and Control of Birth Defect Prevention and Control Committee of Chinese Society of Preventive Medicine have formulated a consensus on the diagnosis, classification and clinical treatment of calcaneal talus bridge based on research home and abroad, and experience on its clinical diagnosis and treatment of well-known experts, with an aim to provide a reference for clinical practice.

Brachydactyly (BD) is a common congenital deformity of the hands and feet resulting from shortening, absence, or fusion of phalanges and metatarsals. Clinically, BD is categorized into isolated, complex and syndromic forms based on the presence of co-morbid congenital manifestations. The diagnosis of BD primarily depends on the examination of the appearance, along with the anteroposterior (AP) X-ray of hands and feet. Bell classified the isolated BD into five types based on the location and number of involved bones. Some BD can be further subdivided into several subtypes according to the severity of the patient's condition and the pathogenic genes. BD shows familial clustering and is mainly inherited in an autosomal dominant manner. The application of high-throughput sequencing has advanced the understanding of the pathogenetic mechanisms of BD. The treatment of BD primarily consists of surgical procedures and rehabilitation training, emphasizing the enhancement functionality and aesthetics of hand and foot. This consensus was initiated by the Hand and Foot Deformities Research Team at Chinese Academy of Medical Sciences Peking Union Medical College Hospital, and refined through multiple rounds of discussions among experts from multiple disciplines. The consensus is intended to facilitate standardized approaches to the diagnosis and treatment of BD, and improve the clinical diagnosis, etiological analysis, clinical intervention, and genetic counseling for BD patients and their families.

Split-hand/foot malformation (SHFM), also known as ectrodactyly (ED), is a group of congenital limb malformations characterized by partial or complete aplasia of the central rays of the hand and/or foot, with variable fusion of the remaining digits. These conditions can severely impact the functions of the limbs, with an incidence ranging from 1/90 000 to 1/8 500, and account for 8% to 17% of all limb malformations. The typical clinical manifestation include median clefts of the hands/feet, syndactyly, and hypoplasia or aplasia of phalanges and metacarpal/metatarsal bones. SHFM are genetically heterogeneous and mainly inherited as an autosomal dominant trait with incomplete penetrance. With the development of genetic technology, early diagnosis of SHFM can be achieved, which may provide crucial information for clinical management. Clinically, plastic and hand-foot surgeons have proposed integrated solutions for aesthetic repair and and functional reconstructions. To standardize the diagnosis and management of SHFM, the Obstetrics and Gynecology Ultrasound Group of Ultrasound Branch of Chinese Medical Association, Clinical Genetics Group of Medical Geneticist Branch of Chinese Medical Doctor Association, and Group of Genetic Disease Prevention and Control, Birth Defect Prevention and Control Committee, Chinese Society of Preventive Medicine has formulated a multidisciplinary expert consensus through discussions by specialists with backgrounds from genetics, plastic surgery, and hand-foot surgery, with an aim to guide precise clinical decision-making, genetic counseling, and personalized interventions.

The International System for Human Cytogenomic Nomenclature (ISCN) is a standardized international nomenclature system established by the International Standing Committee on Human Cytogenomic Nomenclature (ISCN SC). It is designed for describing chromosomal or genomic abnormalities detected by commonly used genetic and genomic techniques including but not limited to karyotyping, fluorescence in situ hybridization, microarray, genome mapping, various region-specific assays, and high-throughput sequencing. With a history spanning over six decades, the ISCN was revised by the ISCN SC in 2024 and officially published in September 2024. This article provides a summary for the updates introduced in the 2024 edition of the International System for Human Cytogenomic Nomenclature.

Arthrogryposis multiplex congenita (AMC) is a clinical syndrome with complex etiology. It is a non-progressive syndrome characterized by joint deformity and stiffness, muscle atrophy, reduction of skin folds and subcutaneous tissue, and contracture of periarticular tissue, and can affect children in whom there are at least 2 or more joint contractures in multiple areas. AMC may be divided into amyoplasia, distal arthrogryposis, central nervous system and neuromuscular diseases which can be diagnosed by prenatal ultrasound and genetic testing, as well as by clinical evaluation, genetic examination, neuromuscular electrophysiological examination, imaging examination and special laboratory examination after birth. The goal of treatment is to improve the self-care ability of children, and the methods mainly include rehabilitation therapy, splint support and orthotic fixation, as well as orthopedic surgery. The Obstetrics and Gynecology Ultrasound Group of the Ultrasound Branch of Chinese Medical Association, Clinical Genetics Group of the Medical Genetics Branch of Chinese Medical Association, and the Genetic Disease Prevention and Control Group of Birth Defects Prevention and Control Professional Committee of Chinese Preventive Medicine Association have organized experts to develop this consensus through multiple rounds of discussions, with an aim to provide reference for clinicians to better understand and standardize the diagnosis and treatment of this disease, and promote the development of related industries.