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We report an index patient with complete insensitivity to pain and a history of painless fractures, joint hypermobility, and behavioral problems. The index patient descends froma familywith notable cases among hismaternal relatives, including his aunt and his mother's first cousin, both of whom suffer from congenital insensitivity to pain. The patient had normal results for prior genetic testing: fragile-X syndrome testing, chromosomal microarray analysis, and exome sequencing. Optical genome mapping detected a homozygous deletion affecting the noncoding 5' untranslated region (UTR) and the first non-coding exon of the SCN9A gene in all affected family members, compatiblewith recessive disease transmission. Pathogenic homozygous loss-of-function variants in the SCN9A gene are associated with impaired pain sensation in humans. Optical genome mapping can thus detect pathogenic structural variants in patients without molecular etiology by standard diagnostic procedures and is a more accessible diagnostic tool than short-read or long-read whole-genome sequencing. [ABSTRACT FROM AUTHOR]

Background: Fontaine progeroid syndrome (FPS, OMIM 612289) is a recently identified genetic disorder stemming from pathogenic variants in the SLC25A24 gene, encoding a mitochondrial carrier protein. It encompasses Gorlin–Chaudry–Moss syndrome and Fontaine–Farriaux syndrome, primarily manifesting as craniosynostosis with brachycephaly, distinctive dysmorphic facial features, hypertrichosis, severe prenatal and postnatal growth restriction, limb shortening, and early aging with characteristic skin changes, phalangeal anomalies, and genital malformations. Cases: All known occurrences of FPS have been postnatally observed until now. Here, we present the first two prenatal cases identified during the second trimester of pregnancy. While affirming the presence of most postnatal abnormalities in prenatal cases, we note the absence of a progeroid appearance in young fetuses. Notably, our reports introduce new phenotypic features like encephalocele and nephromegaly, which were previously unseen postnatally. Moreover, paternal SLC25A24 mosaicism was detected in one case. Conclusions: We present the initial two fetal instances of FPS, complemented by thorough phenotypic and genetic assessments. Our findings expand the phenotypical spectrum of FPS, unveiling new fetal phenotypic characteristics. Furthermore, one case underscores a potential novel inheritance pattern in this disorder. Lastly, our observations emphasize the efficacy of exome/genome sequencing in both prenatal and postmortem diagnosis of rare polymalformative syndromes with a normal karyotype and array‐based comparative genomic hybridization (CGH). [ABSTRACT FROM AUTHOR]

Abstract Background In routine Assisted Reproductive Technology (ART) men with severe oligozoospermia or azoospermia should be informed about the risk of de novo congenital or chromosomal abnormalities in ICSI program. Also the benefits of preimplantation or prenatal genetic diagnosis practice need to be explained to the couple. Methods From a routine ICSI attempt, using ejaculated sperm from male with severe oligozoospermia and having normal karyotype, a 30 years old pregnant woman was referred to prenatal diagnosis in the 17th week for bichorionic biamniotic twin gestation. Amniocentesis was performed because of the detection of an increased foetal nuchal translucency for one of the fetus by the sonographic examination during the 12th week of gestation (WG). Chromosome and DNA studies of the fetus were realized on cultured amniocytes Results Conventional, molecular cytogenetic and microarray CGH experiments allowed us to conclude that the fetus had a de novo pericentromeric inversion associated with a duplication of the 9p22.1-p24 chromosomal region, 46,XY,invdup(9)(p22.1p24) [arrCGH 9p22.1p24 (RP11-130C19 → RP11-87O1)x3]. As containing the critical 9p22 region, our case is in coincidence with the general phenotype features of the partial trisomy 9p syndrome with major growth retardation, microcephaly and microretrognathia. Conclusion This de novo complex chromosome rearrangement illustrates the possible risk of chromosome or gene defects in ICSI program and the contribution of array-CGH for mapping rapidly de novo chromosomal imbalance.

Objectives: To evaluate the failure rate and performance of cell-free DNA (cfDNA) testing, mainly in terms of detection rates for trisomy 21, performed by 2 laboratories using different analytical methods.Methods: cfDNA testing was performed on 2,870 pregnancies with the HarmonyTM Prenatal Test using the targeted digital analysis of selected regions (DANSR) method, and on 2,635 pregnancies with the "Cerba test" using the genome-wide massively parallel sequencing (GW-MPS) method, with available outcomes. Propensity score analysis was used to match patients between the 2 groups. A comparison of the detection rates for trisomy 21 between the 2 laboratories was made.Results: In all, 2,811 patients in the Harmony group and 2,530 patients in the Cerba group had no trisomy 21, 18, or 13. Postmatched comparisons of the patient characteristics indicated a higher no-result rate in the Harmony group (1.30%) than in the Cerba group (0.75%; p = 0.039). All 41 cases of trisomy 21 in the Harmony group and 93 cases in the Cerba group were detected.Conclusions: Both methods of cfDNA testing showed low no-result rates and a comparable performance in detecting trisomy 21; yet GW-MPS had a slightly lower no-result rate than the DANSR method. [ABSTRACT FROM AUTHOR]