Genetic variants of ABCC8 and clinical manifestations in eight Chinese children with hyperinsulinemic hypoglycemia.

BACKGROUND: ABCC8 variants can cause hyperinsulinemia by activating or deactivating gene expression. This study used targeted exon sequencing to investigate genetic variants of ABCC8 and the associated phenotypic features in Chinese patients with hyperinsulinemic hypoglycemia (HH). METHODS: We enrolled eight Chinese children with HH and analyzed their clinical characteristics, laboratory results, and genetic variations. RESULTS: The age at presentation among the patients ranged from neonates to 0.6 years old, and the age at diagnosis ranged from 1 month to 5 years, with an average of 1.3 ± 0.7 years. Among these patients, three presented with seizures, and five with hypoglycemia. One patient (Patient 7) also had microcephaly. All eight patients exhibited ABCC8 abnormalities, including six missense mutations (c. 2521 C > G, c. 3784G > A, c. 4478G > A, c. 4532T > C, c. 2669T > C, and c. 331G > A), two deletion-insertion mutations (c. 3126_3129delinsTC and c. 3124_3126delins13), and one splicing mutation (c. 1332 + 2T > C). Two of these mutations (c. 3126_3129delinsTC and c. 4532T > C) are novel. Six variations were paternal, two were maternal, and one was de novo. Three patients responded to diazoxide and one patient responded to octreotide treatment. All there patients had diazoxide withdrawal with age. Two patients (patients 3 and 7) were unresponsive to both diazoxide and octreotide and had mental retardation. CONCLUSIONS: Gene analysis can aid in the classification, treatment, and prognosis of children with HH. In this study, the identification of seven known and two novel variants in the ABCC8 gene further enriched the variation spectrum of the gene.

Screening/diagnosis of pediatric endocrine disorders through the artificial intelligence model in different language settings.

This study is aimed at examining the impact of ChatGPT on pediatric endocrine and metabolic conditions, particularly in the areas of screening and diagnosis, in both Chinese and English modes. A 40-question questionnaire covering the four most common pediatric endocrine and metabolic conditions was posed to ChatGPT in both Chinese and English three times each. Six pediatric endocrinologists evaluated the responses. ChatGPT performed better when responding to questions in English, with an unreliable rate of 7.5% compared to 27.5% for Chinese questions, indicating a more consistent response pattern in English. Among the reliable questions, the answers were more comprehensive and satisfactory in the English mode. We also found disparities in ChatGPT's performance when interacting with different target groups and diseases, with improved performance for questions posed by clinicians in English and better performance for questions related to diabetes and overweight/obesity in Chinese for both clinicians and patients. Language comprehension, providing incomprehensive answers, and errors in key data were the main contributors to the low scores, according to reviewer feedback. CONCLUSION: Despite these limitations, as ChatGPT continues to evolve and expand its network, it has significant potential as a practical and effective tool for clinical diagnosis and treatment. WHAT IS KNOWN: • The deep learning-based large-language model ChatGPT holds great promise for improving clinical practice for both physicians and patients and has the potential to increase the speed and accuracy of disease screening and diagnosis, as well as enhance the overall efficiency of the medical process. However, the reliability and appropriateness of AI model responses in specific field remains unclear. • This study focused on the reliability and appropriateness of AI model responses to straightforward and fundamental questions related to the four most prevalent pediatric endocrine and metabolic disorders, for both healthcare providers and patients, in different language scenarios. WHAT IS NEW: • The AI model performed better when responding to questions in English, with more consistent, as well as more comprehensive and satisfactory responses. In addition, we also found disparities in ChatGPT's performance when interacting with different target groups and different diseases. • Despite these limitations, as ChatGPT continues to evolve and expand its network, it has significant potential as a practical and effective tool for clinical diagnosis and treatment.

[Treatment of ornithine transcarbamylase deficiency in a child with glyceryl phenylbutyrate]. / è‹¯ä¸é ¸ç”˜æ²¹é ¯æ²»ç–—å„¿ç«¥é¸Ÿæ°¨é ¸æ°¨ç”²é °åŸºè½¬ç§»é ¶ç¼ºä¹ç—‡1例.

Glyceryl phenylbutyrate (GPB) serves as a long-term management medication for Ornithine transcarbamylase deficiency (OTCD), effectively controlling hyperammonemia, but there is a lack of experience in using this medicine in China. This article retrospectively analyzes the case of a child diagnosed with OTCD at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, including a review of related literature. After diagnosis, the patient was treated with GPB, followed by efficacy follow-up and pharmacological monitoring. The 6-year and 6-month-old male patient exhibited poor speech development, disobedience, temper tantrums, and aggressive behavior. Blood ammonia levels peaked at 327 µmol/L; urine organic acid analysis indicated elevated uracil levels; cranial MRI showed extensive abnormal signals in both cerebral hemispheres. Genetic testing revealed de novo mutation in the OTC gene (c.241T>C, p.S81P). Blood ammonia levels were approximately 43, 80, and 56 µmol/L at 1, 2, and 3 months after starting GPB treatment, respectively. During treatment, blood ammonia was well-controlled without drug-related adverse effects. The patient showed improvement in developmental delays, obedience, temperament, and absence of aggressive behavior.

Genotypic and phenotypic features of dyslipidemia in a sample of pediatric patients in China.

BACKGROUND: Dyslipidemia, especially hypercholesterolemia is of significant clinical interest. Precise diagnosis is not paid enough attention to about the management of pediatric patients with hypercholesterolemia, which is especially apparent in China. Given this, we designed this study to confirm the specific molecular defects associated with hypercholesterolemia using whole-exome sequencing (WES) to be helpful for precise diagnosis and treatment. METHODS: Pediatric patients were enrolled using specific criteria and their clinical information were recorded for later evaluation in conjunction with the WES completed for each of these patients. RESULTS: Our criteria allowed for the initial enrollment of 35 patients, 30 of whom (aged 1.02-12.99 years) underwent successful genetic sequencing and clinical investment. Positive results were obtained in 63.33% (19/30) of these patients. We identified 25 variants in 30 pediatric patients with persistent hypercholesterolemia, seven of them were novel and variants in LDLR and ABCG5/ABCG8 ranks first and second, respectively. Further analysis revealed that the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB) and lipoprotein (a) were higher in patients with positive genetic results. CONCLUSION: Our study enriched the genetic and phenotypic spectra for hypercholesterolemia in young patients. Genetic testing is important for the prognostics and treatment of pediatric patients. Heterozygous ABCG5/8 variants may be underestimated in pediatric patients with hypercholesterolemia.

[Clinical characteristics and genetic analysis of a patient with STISS syndrome due to variant of PSMD12 gene].

OBJECTIVE: To investigate the clinical and genetic characteristics of a patient with STISS syndrome due to variant of PSMD12 gene. METHODS: Clinical data and result of genetic testing of a patient who was admitted to Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine on October 4, 2020 were analyzed, together with a review of relevant literature. RESULTS: The patient was found to harbor a heterozygous c.601C>T (p.Arg201*) nonsense variant of the PSMD12 gene, which was unreported previously. Clinically, the height of the patient has differed significantly from reported in the literature. An extremely rare case of STISS syndrome due to variant of the PSMD12 gene has been diagnosed. CONCLUSION: Whether the severely short stature is part of the clinical spectrum for PSMD12 gene variants needs to be further explored, and the efficacy and safety of growth hormone therapy has yet to be determined.

[Identification of a child with Teebi hypertelorism syndrome 1 due to variant of SPECC1L gene].

OBJECTIVE: To explore the clinical characteristics and genetic basis of a child with Teebi hypertelorism syndrome 1 (TBHS1). METHODS: A child with TBHS1 who was admitted to the Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine on July 13, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 13-year-old male, had manifested delayed growth and development. WES results revealed that he has harbored a heterozygous c.1244A>G variant of the SPECC1L gene, which was verified to be de novo in origin. The variant has not been included in the HGMD and gnomAD databases. As predicted by online software including PolyPhen-2, SIFT, and Mutation Taster, the variant may affect the function of protein domain. And PyMOL software has predicted that the structural stability of SPECC1L protein (p.Gln415Arg) might be reduced. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PM6+PM1+PP4+PM2_Supporting+PP3). CONCLUSION: The heterozygous c.1244A>G variant of the SPECC1L gene probably underlay the TBHS1 in this child. Above finding has expanded the genotypic and phenotypic spectrum of the SPECC1L gene and provided a basis for the clinical diagnosis of this child.

Clinical characteristics and genetic analysis of a child with specific type of diabetes mellitus caused by missense mutation of GATA6 gene. / 一例GATA6åŸºå› å˜å¼‚å¼•èµ·å„¿ç«¥ç‰¹æ®Šç±»åž‹ç³–å°¿ç— çš„ä¸´åºŠç‰¹ç‚¹åŠåŸºå› å˜å¼‚åˆ†æž.

A 2-year-old boy was admitted to Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine in Nov 30th, 2018, due to polydipsia, polyphagia, polyuria accompanied with increased glucose levels for more than 2 weeks. He presented with symmetrical short stature [height 81 cm (－2.2 SD), weight 9.8 kg (－2.1 SD), body mass index 14.94 kg/m2 (P10-P15)], and with no special facial or physical features. Laboratory results showed that the glycated hemoglobin A1c was 14%, the fasting C-peptide was 0.3 ng/mL, and the islet autoantibodies were all negative. Oral glucose tolerance test showed significant increases in both fasting and postprandial glucose, but partial islet functions remained (post-load C-peptide increased 1.43 times compared to baseline). A heterozygous variant c.1366C>T (p.R456C) was detected in GATA6 gene, thereby the boy was diagnosed with a specific type of diabetes mellitus. The boy had congenital heart disease and suffered from transient hyperosmolar hyperglycemia after a patent ductus arteriosus surgery at 11 months of age. Insulin replacement therapy was prescribed, but without regular follow-up thereafter. The latest follow-up was about 3.5 years after the diagnosis of diabetes when the child was 5 years and 11 months old, with the fasting blood glucose of 6.0-10.0 mmol/L, and the 2 h postprandial glucose of 17.0-20.0 mmol/L.

Evaluating the variety of GNAS inactivation disorders and their clinical manifestations in 11 Chinese children.

BACKGROUND: The GNAS gene on chromosome 20q13.3, encodes the alpha-subunit of the stimulatory G protein, which is expressed in most tissues and regulated through reciprocal genomic imprinting. Disorders of GNAS inactivation produce several different clinical phenotypes including pseudohypoparathyroidism (PHP), pseudopseudohypoparathyroidism (PPHP), progressive osseous heteroplasia (POH), and osteoma cutis (OC). The clinical and biochemical characteristics overlap of PHP subtypes and other related disorders presents challenges for differential diagnosis. METHODS: We enrolled a total of 11 Chinese children with PHP in our study and analyzed their clinical characteristics, laboratory results, and genetic mutations. RESULTS: Among these 11 patients, nine of them (9/11) presented with resistance to parathyroid hormone (PTH); and nine (9/11) presented with an Albright's hereditary osteodystrophy (AHO) phenotype. GNAS abnormalities were detected in all 11 patients, including nine cases with GNAS gene variations and two cases with GNAS methylation defects. These GNAS variations included an intronic mutation (c.212 + 3_212 + 6delAAGT), three missense mutations (c.314C > T, c.308 T > C, c.1123G > T), two deletion mutations (c.565_568delGACT*2, c.74delA), and two splicing mutations (c.721 + 1G > A, c.432 + 1G > A). Three of these mutations, namely, c.314C > T, c.1123G > T, and c.721 + 1G > A, were found to be novel. This data was then used to assign a GNAS subtype to each of these patients with six cases diagnosed as PHP1a, two cases as PHP1b, one as PPHP, and two as POH. CONCLUSIONS: Evaluating patients with PTH resistance and AHO phenotype improved the genetic diagnosis of GNAS mutations significantly. In addition, our results suggest that when GNAS gene sequencing is negative, GNAS methylation study should be performed. Early genetic detection is required for the differential diagnosis of GNAS disorders and is critical to the clinician's ability to distinguish between heterotopic ossification in the POH and AHO phenotype.

[Frontometaphyseal dysplasia 1 caused by variant of FLNA gene in a case].

OBJECTIVE: To explore the clinical and genetic characteristics of a child with frontometaphyseal dysplasia 1 (FMD1) due to variant of FLNA gene. METHODS: Clinical phenotype of the patient was analyzed. Whole exome sequencing (WES) was carried out to detect pathogenic genetic variants. Sanger sequencing was used to verify the result in his parents. RESULTS: The 2-year-and-9-month-old boy presented with facial dysmorphism (supraorbital hyperostosis, down-slanting palpebral fissure and ocular hypertelorism), skeletal deformities (bowed lower limbs, right genu valgum, left genu varus, slight deformity of index and middle fingers, and flexion contracture of little fingers). He also had limited left elbow movement. High-throughput sequencing revealed that he has carried a de novo heterogeneous c.3527G>A (p.Gly1176Glu) missense variant of the FLNA gene. The same variant was found in neither parent. CONCLUSION: The clinical manifestations of FMD1 such as joint contracture and bone dysplasia can occur in infancy and deteriorate with age, and require long-term follow-up and treatment. Above finding has expanded the spectrum of FLNA gene variants.

[Analysis of ALMS1 gene variants in seven patients with Alström syndrome].

OBJECTIVE: To explore the genetic basis for 7 patients with Alström syndrome. METHODS: DNA was extracted from peripheral blood samples of the patients and their parents. Whole exome sequencing was carried out for the patients. Suspected variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: Genetic testing revealed 12 variants of the ALMS1 gene among the 7 patients, including 7 nonsense and 5 frameshift variants, which included c.5418delC (p.Tyr1807Thrfs*23), c.10549C>T (p.Gln3517*), c.9145dupC (p.Thr3049Asnfs*12), c.10819C>T (p.Arg3607*), c.5701_5704delGAGA (p.Glu1901Argfs*18), c.9154_9155delCT (p.Cys3053Serfs*9), c.9460delG (p.Val3154*), c.9379C>T (p.Gln3127*), c.12115C>T (p.Gln4039*), c.1468dupA (p.Thr490Asnfs*15), c.10825C>T (p.Arg3609*) and c.3902C>A (p.Ser1301*). Among these, c.9154_ 9155delCT, c.9460delG, c.9379C>T, and c.1468dupA were unreported previously. Based on the standards and guidelines of American College of Medical Genetics and Genomics, the c.9379C>T and c.12115C>T variants of the ALMS1 gene were predicted to be likely pathogenic (PVS1+PM2), whilst the other 10 variants were predicted to be pathogenic (PVS1+ PM2+ PP3+PP4). CONCLUSION: ALMS1 variants probably underlay the Alström syndrome in the 7 patients, and genetic testing can provide a basis for the clinical diagnosis of this syndrome. The discovery of four novel variants has expanded the mutational spectrum of Alström syndrome.

[Clinical and genetic analysis of an infant with combined pituitary hormone deficiency due to POU1F1 gene variants].

OBJECTIVE: To explore the clinical characteristics and genetic basis for an infant featuring combined pituitary hormone deficiency. METHODS: Clinical data and results of DNA sequencing of the child were analyzed. RESULTS: The 10-month-old male infant presented with recurrent hypoglycemia, extremely poor appetite and constipation, and severe growth retardation from 2 months on, in addition with pituitary hormone deficiency involving growth hormone, thyroid stimulating hormone, and prolactin. Next generation sequencing revealed a novel heterozygous c.767-769del (p.Glu256del) variant of the POU1F1 gene in the patient. CONCLUSION: The patient was diagnosed with combined pituitary hormone deficiency due to the POU1F1 gene variant, for which replacement therapy including thyroxine and growth hormone was provided. Hypoglycemia is unusual in patients carrying POU1F1 gene variants and requires close attention in clinical practice. For children with multiple pituitary hormone deficiency, genetic testing should be recommended to determine the cause.

Molecular and phenotypic spectrum of Noonan syndrome in Chinese patients.

Noonan syndrome (NS) is a common autosomal dominant/recessive disorder. No large-scale study has been conducted on NS in China, which is the most populous country in the world. Next-generation sequencing (NGS) was used to identify pathogenic variants in patients that exhibited NS-related phenotypes. We assessed the facial features and clinical manifestations of patients with pathogenic or likely pathogenic variants in the RAS-MAPK signaling pathway. Gene-related Chinese NS facial features were described using artificial intelligence (AI).NGS identified pathogenic variants in 103 Chinese patients in eight NS-related genes: PTPN11 (48.5%), SOS1 (12.6%), SHOC2 (11.7%), KRAS (9.71%), RAF1 (7.77%), RIT1 (6.8%), CBL (0.97%), NRAS (0.97%), and LZTR1 (0.97%). Gene-related facial representations showed that each gene was associated with different facial details. Eight novel pathogenic variants were detected and clinical features because of specific genetic variants were reported, including hearing loss, cancer risk due to a PTPN11 pathogenic variant, and ubiquitous abnormal intracranial structure due to SHOC2 pathogenic variants. NGS facilitates the diagnosis of NS, especially for patients with mild/moderate and atypical symptoms. Our study describes the genotypic and phenotypic spectra of NS in China, providing new insights into distinctive clinical features due to specific pathogenic variants.

[Analysis of clinical manifestation and genetic mutation in a child with X-linked chondrodysplasia punctata 2].

OBJECTIVE: To analyze clinical manifestations and genetic mutation in a child with severe short stature and other malformations. METHODS: The child has undergone history taking and physical examination. Genome DNA was extracted from peripheral blood samples of the proband and her family members. Candidate genes were captured with Agilent SureSelect and sequenced on an Illumina platform. Suspected mutation was verified by Sanger sequencing. RESULTS: The patient, a six-year-and-10-month old girl, presented with non-symmetrical short stature, dysmorphism, abnormalities of limbs and spine, amblyopia of left eye, and cataract of right eye, in addition with frequent respiratory infection and micturition. Laboratory testing suggested 25-hydroxy vitamin D deficiency (18.9 ng/mL). Spine X-ray showed multiple malformations with centrums. Her mother also featured short stature (138 cm). Her aunt had short stature (130 cm) and limb-length discrepancy. Her little brother was 2.5 years old, and his height was 81 cm (-3.4 SD). Exome sequencing revealed a heterozygous mutation c.184C to T (p.Arg62Trp) in the proband and her mother. The same mutation was not found in her father and brother. CONCLUSION: The patient was diagnosed with X-linked chondrodysplasia punctata 2. Mutation of the EBP gene probably underlied the disease in this family.

SOPH Syndrome with Growth Hormone Deficiency, Normal Bone Age, and Novel Compound Heterozygous Mutations in NBAS.

BACKGROUND: Short stature with optic atrophy and Pelger-Huet anomaly (SOPH; MIM 614800) syndrome is a genetic disease caused by mutation in the neuroblastoma amplified sequence (NBAS) gene. CASE REPORT: We present a 11-year-old Chinese boy with SOPH syndrome, growth hormone deficiency with a normal bone age. Gene sequencing in the patient revealed a novel compound heterozygous mutation of c.5752A > C (Thr1918Pro) and c.500_501delTT (Phe167Cysfs*7) in the NBAS gene. CONCLUSIONS: To our best knowledge, these novel mutations in the NBAS gene have not been reported. Normal bone age with growth hormone deficiency in this patient is different from the patients with SOPH syndrome that have been previously reported. These findings enrich the mutant spectrum of the NBAS gene and add our understanding of SOPH syndrome.

Biallelic mutations in GPD1 gene in a Chinese boy mainly presented with obesity, insulin resistance, fatty liver, and short stature.

Biallelic mutations in the GPD1 gene cause a rare autosomal recessive inherited disease known as transient infantile hypertriglyceridemia (OMIM #614480). To date, only five pathogenic variants have been reported in 15 patients from three studies. The clinical symptoms of the affected individuals present a certain degree of heterogeneity. Here, we describe a chinese adolescent patient who mainly presented with obesity, insulin resistance, fatty liver, and short stature. Targeted next-generation sequencing revealed a novel compound heterozygous variant in GPD1 gene (c.220-2A>G and c.820G>A; p.Ala274Thr). In vitro studies demonstrated that the Ala274Thr variant induced a decrease in GPD1 protein expression. Further in vitro investigation of the splicing pattern in a minigene construct in HEK293 cells showed that the c.220-2A>G variant generated an altered transcript with one cryptic splice site in exon 3, resulting in the loss of 69 bases in exon 3 (c.220_288del, p.74_96del). This is the first report involving an Asian who harbored GPD1 mutations. Our work not only expands the mutant spectrum of the GPD1 gene but also provides new insights on its resulting phenotype.

Clinical and Molecular Characterization of Patients with Fructose 1,6-Bisphosphatase Deficiency.

Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare, autosomal recessive inherited disease caused by the mutation of the FBP1 gene, the incidence is estimated to be between 1/350,000 and 1/900,000. The symptoms of affected individuals are non-specific and are easily confused with other metabolic disorders. The present study describes the clinical features of four Chinese pediatric patients who presented with hypoglycemia, hyperlactacidemia, metabolic acidosis, and hyperuricemia. Targeted-next generation sequencing using the Agilent SureSelect XT Inherited Disease Panel was used to screen for causal variants in the genome, and the clinically-relevant variants were subsequently verified using Sanger sequencing. Here, DNA sequencing identified six variations of the FBP1 gene (NM_000507.3) in the four patients. In Case 1, we found a compound heterozygous mutations of c.704delC (p.Pro235GlnfsX42) (novel) and c.960_961insG (p.Ser321Valfs) (known pathogenic). In Case 2, we found a compound heterozygous mutations of c.825 + 1G>A and c.960_961insG (both were known pathogenically). In Case 3, a homozygous missense mutation of c.355G>A (p.Asp119Asn) (reported in ClinVar database without functional study) was found. Case 4 had a compound heterozygous mutations c.720_729del (p.Tyr241GlyfsX33) (novel) and c.490G>A (p.Gly164Ser) (known pathogenically). Further in vitro studies in the COS-7cell line demonstrated that the mutation of ASP119ASN had no impact on protein expression, but decreased the enzyme activity, and with which the clinical significance of Asp119Asn can be determined to be likely pathogenic. This report not only expands upon the known spectrum of variation of the FBP1 gene, but also deepens our understanding of the clinical features of FBPase deficiency.

[A boy with Meier-Gorlin syndrome carrying a novel ORC6 mutation and uniparental disomy of chromosome 16].

OBJECTIVE: To identify the genetic cause for a 11-year-old Chinese boy with Meier-Gorlin syndrome (MGS). METHODS: Chromosomal microarray analysis (CMA) was used to detect potential variations, while whole exome sequencing (WES) was used to identify sequence variants. Sanger sequencing was used to confirm the suspected variants. RESULTS: The boy has featured short stature, microtia, small patella, slender body build, craniofacial anomalies, and small testes with normal gonadotropin. A complete uniparental disomy of chromosome 16 was revealed by CMA. WES has identified a novel homozygous mutation c.67A>G (p.Lys23Glu) in ORC6 gene mapped to chromosome 16. As predicted by Alamut functional software, the mutation may affect the function of structural domain of the ORC6 protein. CONCLUSION: The patient is probably the first diagnosed MGS case in China, who carried a novel homozygous mutation of the ORC6 gene and uniparental disomy of chromosome 16. The effect of this novel mutation on the growth and development needs to be further investigated.

[Endocrine and metabolic features of female children with Prader-Willi syndrome: an analysis of 4 cases].

This article reports the clinical features and endocrine and metabolic features of 4 children with Prader-Willi syndrome (PWS). All the patients were female and aged 6-12 years at diagnosis. All of them had clinical manifestations of obesity, unusual facies, developmental retardation, and intellectual disability. Genetic detection showed that 2 patients had paternal deletion of the 15q11.2-q13 region, one patient had maternal autodiploid in the 15q11.2-q13 region, and one patient had no abnormality in the 15q11.2-q13 region. All patients had varying degrees of endocrine and metabolic disorders: 2 patients had short stature, among whom one had delayed appearance of secondary sex characteristics and the other one had type 2 diabetes; one patient had insulin resistance and no mammary gland development; one patient had a body height of P3-P10 and precocious puberty. Patients with PWS have various endocrine disorders, so long-term endocrine follow-up and management is very important.

A de novo variant in ZBTB18 gene caused autosomal dominant non-syndromic intellectual disability 22 syndrome: A case report and literature review.

RATIONALE: Autosomal dominant non-syndromic intellectual disability 22 is a rare genetic disorder caused by the ZBTB18 gene. This disorder affects various parts of the body, leading to intellectual disability. It is noteworthy that only 31 cases of this disorder have been reported thus far. As the symptom severity may differ, doctors may face challenges in diagnosing it accurately. It is crucial to be familiar with this disorder's symptoms to receive proper diagnosis and essential medical care. PATIENT CONCERNS: There is a case report of a 6-year-old boy who had an unexplained thyroid abnormality, global developmental delay, and an abnormal signal of white matter in brain MRI. However, he did not have growth retardation, microcephaly, corpus callosum hypoplasia, epilepsy, or dysmorphic facial features. Clinical whole exome sequencing revealed a de novo pathogenic variant in the ZBTB18 gene (c.1207delC, p. Arg403Alafs*60), which is a previously unreported site. This variant causes the premature termination of peptide chain synthesis, leading to incomplete polypeptide chains. DIAGNOSES: Autosomal dominant non-syndromic intellectual and disability 22 syndrome and thyroid dysfunction. INTERVENTIONS: Rehabilitation training. OUTCOMES: The individual is experiencing difficulty with their motor skills, appearing clumsier while running. He struggles with expressing themselves and forming complete sentences, relying mostly on gestures and pointing. LESSONS: The clinical presentations of mental retardation, autosomal dominant, type 22 (MRD22) are complicated and varied. Although early diagnosis can be made according to typical clinical symptoms, whole exome sequencing is necessary for diagnosing MRD22, as our study indicates.

Molecular and phenotypic characteristics of Bardet-Biedl syndrome in Chinese patients.

BACKGROUND: Bardet-Biedl syndrome (BBS) is a type of non-motile ciliopathy. To date, 26 genes have been reported to be associated with BBS. However, BBS is genetically heterogeneous, with significant clinical overlap with other ciliopathies, which complicates diagnosis. Disability and mortality rates are high in BBS patients; therefore, it is urgent to improve our understanding of BBS. Thus, our study aimed to describe the genotypic and phenotypic spectra of BBS in China and to elucidate genotype-phenotype correlations. METHODS: Twenty Chinese patients diagnosed with BBS were enrolled in this study. We compared the phenotypes of Chinese BBS patients in this study with those from other countries to analyze the phenotypic differences across patients worldwide. In addition, genotype-phenotype correlations were described for our cohort. We also summarized all previously reported cases of BBS in Chinese patients (71 patients) and identified common and specific genetic variants in the Chinese population. RESULTS: Twenty-eight variants, of which 10 are novel, in 5 different BBS-associated genes were identified in 20 Chinese BBS patients. By comparing the phenotypes of BBSome-coding genes (BBS2,7,9) with those of chaperonin-coding genes (BBS10,12), we found that patients with mutations in BBS10 and 12 had an earlier age of onset (1.10 Vs. 2.20, p < 0.01) and diagnosis (4.64 Vs. 13.17, p < 0.01), whereas patients with mutations in BBS2, 7, and 9 had a higher body mass index (28.35 Vs. 24.21, p < 0.05) and more vision problems (p < 0.05). Furthermore, in 91 Chinese BBS patients, mutations were predominant in BBS2 (28.89%) and BBS7 (15.56%), and the most frequent variants were in BBS2: c.534 + 1G > T (10/182 alleles) and BBS7: c.1002delT (7/182 alleles), marking a difference from the genotypic spectra of BBS reported abroad. CONCLUSIONS: We recruited 20 Chinese patients with BBS for genetic and phenotypic analyses, and identified common clinical manifestations, pathogenic genes, and variants. We also described the phenotypic differences across patients worldwide and among different BBS-associated genes. This study involved the largest cohort of Chinese patients with BBS, and provides new insights into the distinctive clinical features of specific pathogenic variants.