[Diagnosis of a patient with Spinocerebellar ataxia type 29 due to a novel variant of ITPR1 gene].

OBJECTIVE: To explore the clinical and genetic characteristics of a child with spinocerebellar ataxia type 29 (SCA29) due to novel variant of the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) gene. METHODS: The child was subjected high-throughput sequencing, and candidate variant was verified by Sanger sequencing of his family members. RESULTS: The child was found to harbor a c.800C>T (p.T267M) variant of the ITPR1 gene, which was not found in his parents and their fetus. The variant has occurred in a hotspot of the ITPR1 gene variants and was unreported before in China. Based on his clinical and genetic characteristics, the child was diagnosed with SCA29. CONCLUSION: The novel heterozygous c.800C>T (p.T267M) of the ITPR1 gene probably underlay the SCA29 in this child.

Identification of a novel mutation of NOG in family with proximal symphalangism and early genetic counseling.

BACKGROUND: Proximal symphalangism is a rare disease with multiple phenotypes including reduced proximal interphalangeal joint space, symphalangism of the 4th and/or 5th finger, as well as hearing loss. At present, at least two types of proximal symphalangism have been identified in the clinic. One is proximal symphalangism-1A (SYM1A), which is caused by genetic variants in Noggin (NOG), another is proximal symphalangism-1B (SYM1B), which is resulted from Growth Differentiation Factor 5 (GDF5) mutations. CASE PRESENTATION: Here, we reported a Chinese family with symphalangism of the 4th and/or 5th finger and moderate deafness. The proband was a 13-year-old girl with normal intelligence but symphalangism of the 4th finger in the left hand and moderate deafness. Hearing testing and inner ear CT scan suggested that the proband suffered from structural deafness. Family history investigation found that her father (II-3) and grandmother (I-2) also suffered from hearing loss and symphalangism. Target sequencing identified a novel heterozygous NOG mutation, c.690C > G/p.C230W, which was the genetic lesion of the affected family. Bioinformatics analysis and public databases filtering further confirmed the pathogenicity of the novel mutation. Furthermore, we assisted the family to deliver a baby girl who did not carry the mutation by genetic counseling and prenatal diagnosis using amniotic fluid DNA sequencing. CONCLUSION: In this study, we identified a novel NOG mutation (c.690C > G/p.C230W) by target sequencing and helped the family to deliver a baby who did not carry the mutation. Our study expanded the spectrum of NOG mutations and contributed to genetic diagnosis and counseling of families with SYM1A.

Case report: Whole exome sequencing identified a novel mutation (p.Y301H) of MAF in a Chinese family with congenital cataracts.

Background: Congenital cataracts stand as the primary cause of childhood blindness globally, characterized by clouding of the eye's lens at birth or shortly thereafter. Previous investigations have unveiled that a variant in the V-MAF avian musculoaponeurotic-fibrosarcoma oncogene homolog (MAF) gene can result in Ayme-Gripp syndrome and solitary cataract. Notably, MAF mutations have been infrequently reported in recent years. Methods: In this investigation, we recruited a Chinese family with non-syndromic cataracts. Whole exome sequencing and Sanger sequencing were applied to scrutinize the genetic anomaly within the family. Results: Through whole exome sequencing and subsequent data filtration, a new mutation (NM_005360, c.901T>C/p.Y301H) in the MAF gene was detected. Sanger sequencing validated the presence of this mutation in another affected individual. The p.Y301H mutation, situated in an evolutionarily preserved locus, was not detected in our 200 local control cohorts and various public databases. Additionally, multiple bioinformatic programs predicted that the mutation was deleterious and disrupted the bindings between MAF and its targets. Conclusion: Hence, we have documented a new MAF mutation within a Chinese family exhibiting isolated congenital cataracts. Our study has the potential to broaden the spectrum of MAF mutations, offering insights into the mechanisms underlying cataract formation and facilitating genetic counseling and early diagnosis for congenital cataract patients.

Radio frequency ablation for the intrauterine treatment of giant placental chorioangioma associated with fetal compromise: A case report.

Giant placental chorioangiomas associated with fetal hyperdynamic circulation complications are rare to see. Here, we summarized a case of giant placental chorioangioma associated with fetal anemia and heart failure treated by radiofrequency ablation (RFA) combined with cordocentesis and intrauterine transfusion. The sonographic appearance of the placental chorioangioma was atypical which was isoechoic with unclear boundary. RFA was performed successfully at 27 weeks of gestation, when the chorioangioma has increased to 17.0 × 10.6 × 12.3 cm3 . Unfortunately, intrauterine fetal demise was found on the first day after operation. After induction of labor, it was pathologically confirmed as placental chorioangioma.

Intrauterine management and outcomes of persistent fetal atrial flutter: A case report.

BACKGROUND: Fetal atrial flutter (AF), accounting for 30% of all fetal tachyarrhythmias, predominantly (over 80%) manifests as a 2:1 atrioventricular conduction. Swift referral and timely intervention become imperative in instances of severe persistent arrhythmia. CASE PRESENTATION: We discuss the case of a 32-year-old multiparous Chinese woman, at 30+2 weeks of gestation, wherein an ultrasonographic examination revealed persistent fetal AF (atrial rate ranging from 219 to 445 beats/min and ventricular rate from 219 to 228 beats/min, with a 2:1 or 1:1 down transmission) and minor ascites. Despite the maternal ingestion of digoxin and sotalol, the fetal heart rhythm remained uncorrected. Following this, at 32+3 weeks of gestation, an intramuscular injection of cedilanid, guided by ultrasound, was administered to the fetus. Postoperatively, the fetal ventricular rate demonstrated a decline after 6 days, and the ascites resolved. Subsequently, at 33+3 weeks, a cesarean section was necessitated due to maternal intolerance to the medication, resulting in the delivery of the infant. Remarkably, the infant's cardiac rhythm spontaneously converted to sinus rhythm within 5 min of birth. A follow-up conducted 1 year postpartum revealed no recurrence of AF. CONCLUSIONS: This case illustrates that in the event of transplacental drug treatment failure, intrauterine therapeutic intervention should be considered. Moreover, it highlights the encouraging prognosis associated with fetal AF, as the cardiac rhythm spontaneously reverted to sinus rhythm postbirth in this instance.

Prenatal diagnosis and neonatal phenotype of a de novo microdeletion of 17p11.2p12 associated with Smith-Magenis syndrome and external genital defects.

Smith-Magenis syndrome (SMS, OMIM: 182290) is a multiple congenital anomalies and intellectual disability syndrome due to a 3.45 Mb microdeletion involving 17p11.2 and is estimated to occur about one in 25,000 births. Up to now, the ultrasound findings of the foetus with SMS and their external genital defects in patients are rarely reported. This case indicates that foetus with SMS may presentpolyhydramnios and ventriculomegaly in the second trimester. The newborn male patient had an abnormal phenotype in which he has micropenis and his anus is close to the perineal body. The identification of this case may further expand the phenotypic spectrum of this genetic disorder.