Case Reports in Genetics最新文献

Uniparental disomy (UPD), the inheritance of two copies of a chromosome from one parent, can lead to recessive genetic disorders or imprinting effects. We report a case of autosomal recessive glycogen storage disease type 4 (GSD IV) due to maternal UPD of chromosome 3, representing the first reported instance of UPD leading to this rare disorder. To avoid an unjustified claim of misattributed paternity, the possibility of UPD should always be kept in mind in cases with the unique finding of the homozygous pathogenic variant only present in one parent. This case highlights the critical role of genetic counseling in uncovering rare genetic conditions and emphasizes the need for continued awareness of UPD in clinical genetics.

Deletions within the chromosomal locus 1p31.1 are rare, with only a limited number of documented cases. The typical clinical presentation includes intellectual disability, failure to thrive, and craniofacial abnormalities. Some cases may also present with cardiac, gastrointestinal, and genitourinary malformations. Variability in deletion size contributes to a broad spectrum of clinical phenotypes, and a comprehensive understanding of the syndrome's manifestations is still evolving. This case study aims to provide additional insights into 1p31.1 microdeletion syndrome, enhancing knowledge of its genetic and phenotypic characteristics to improve recognition by clinicians. Here, we report a case featuring a 14.385 Mb deletion isolated to the 1p31.1 region, encompassing 41 genes. The deletion manifested with microcephaly, distinctive facial morphology, hypotonia, developmental delay, bilateral cryptorchidism, and flat feet. Notably, our case also exhibited congenital thickening of the lingual and labial frenulum, a trait not typically associated with this deletion.

[This corrects the article DOI: 10.1155/2024/8099373.].

Uniparental disomy (UPD) constitutes an unconventional mode of inheritance that disrupts the typical biparental genetic contribution and may result in phenotypic abnormalities. This report centers on a patient diagnosed with Bartter syndrome Type 1, attributed to a homozygous pathogenic variant in SLC12A1 unmasked by mosaic paternal UPD of chromosome 15. We hypothesize that this pattern (or constellation) emerged from a trisomy rescue event, resulting in two distinct cell lines. Concurrently, the unmasking of a pathogenic paternal SLC12A1 variant by trisomy rescue resulted in the manifestation of Bartter syndrome Type 1. The maternally derived ring chromosome 15 and its impact on nondisjunction and UPD elucidate a unique etiology of Bartter syndrome. Furthermore, the presence of a pathogenic paternal SLC12A1 variant underscores the pivotal role of trisomic rescue and paternal UPD in unveiling a recessive variant.

Neonatal liver disease is a broad entity. When it presents in conjunction with other abnormalities, it raises the question of a potential underlying genetic cause. Etiologies that were once difficult to diagnose are becoming more readily identifiable with the arrival of next-generation sequencing. We present a rare cause of neonatal liver disease, a FOCAD gene variant, that was determined to be the most likely cause of an infant's liver disease and other findings. This case adds to only a few reports in the literature on this presentation in the neonatal period.

Achromatopsia (ACHM) (MIM: 262300) is an autosomal recessive disorder characterized by reduced visual acuity and color blindness. In this report, we review the case of a 14-year-old male patient diagnosed with achromatopsia with a history of retinal dystrophy, cone dysfunction with normal dark-adapted response on ERG, congenital nystagmus, farsightedness, and astigmatism. The diagnostic exome sequencing previously revealed a single maternally inherited pathogenic CNGB3 variant (c.1148delC, p.(T383lfs∗13). Following enrollment in the Undiagnosed Rare Disease Clinic (URDC) at Indiana University School of Medicine (IUSM), genome sequencing (GS) identified a second CNGB3 known variant c.1663-1205G > A p.(Gly555Leufs∗33), which was classified as likely pathogenic. Identification of this variant in the patient provided the evidence needed for a molecular diagnosis and ended a 15-year diagnostic odyssey for the patient and his family. With a diagnosis, the patient is eligible for gene therapy and qualifies for the state-run Vocational Rehabilitation Program and bioptic driving.

Nephronophthisis (NPHP) is a hereditary renal disorder characterized by the progression to end-stage renal disease (ESRD) at a young age. Our understanding of this disorder continues to improve as we identify more genes and gene variants associated with NPHP. In this report, we present a young patient with newly diagnosed advanced renal impairment and a strong family history of ESRD at a young age. The patient's kidney biopsy showed features suggestive of severe chronic interstitial nephritis, along with histopathological findings of advanced renal disease. Genetic testing revealed a novel variant in the IQCB1/NPHP5 gene, which is autosomal recessive. Family genetic analysis revealed that the patient's parents and two of his children are heterozygous for the identified variant, while two siblings with ESRD are homozygous for the IQCB1 p.(Ala486Asp) variant. Unlike previously described mutations in the IQCB1/NPHP5 gene, the patient and his affected siblings do not have retinitis pigmentosa. We report this novel gene variant in a Saudi family, describe its associated clinical features, and present the results of the family segregation analysis.

Dep domain-containing Protein 5 (DEPDC5), encoded by the gene DEPDC5, regulates the cell cycle by inhibiting the mTORC1 pathway in response to amino acid deficiency. Loss of function DEPDC5 variants are recognized to present as focal familial epilepsy; however, associations with comorbid brain malformations and neurodevelopmental disorders have also been reported. mTOR inhibitors were found to benefit DEPDC5-knockout mice. Fragile X syndrome (FXS) is an X-linked neurodevelopmental disorder caused by loss of function of FMR1, and females are expected to have milder neurodevelopmental presentations than males. The reported individual is a 17-year-old female diagnosed with FXS at 1 year of age, but the severity of her neuropsychiatric symptoms prompted further genetic testing at age 14, revealing a likely pathogenic c.4307_4310del DEPDC5 variant. Following this diagnosis, she was started on the mTOR inhibitor sirolimus without significant clinical response. She has never been diagnosed with epilepsy; however, her DEPDC5 and FXS dual diagnosis was thought explanatory for her presentation. A review of 213 previously reported individuals with DEPDC5-related disorder demonstrated that 15.2% of individuals do not have epilepsy, 24.3% have intellectual disability, and 33.8% have brain malformations. Her lack of response to sirolimus may represent the presence of a critical treatment window for mTOR inhibitors in neurodevelopmental disorders.

We present a case of an optic nerve coloboma in a 10-month-old girl found to have compound heterozygous USH2A variants. There were no other dysmorphic features or ocular developmental anomalies. To our knowledge, this is the first report in literature of a concomitant optic nerve coloboma in a case of nonsyndromic retinitis pigmentosa related to USH2A variants.

Background: Bartter syndrome is a rare genetic illness characterized by impairment in kidney function caused by different gene defects. The primary pathogenic mechanism of Bartter syndrome is defective salt reabsorption, predominantly in the thick ascending limb of the loop of Henle. Case Presentation: Here, we present a case series between 2 siblings diagnosed with Bartter syndrome through clinical and genetic analyses. Both patients presented with severe dehydration secondary to polyuria which caused persistent electrolyte imbalances. However, the second sibling presented with hydrocephalus which may be associated with Bartter Syndrome. Genetic analysis determined the presence of a known pathogenic mutation and a novel mutation in the CLCNKB variant. Conclusions: Bartter syndrome Type III is a genetic disorder that must be identified clinically without delay, as it typically manifests as acute dehydration due to polyuria and vomiting. Hydrocephalus, although cannot be concluded to be a complication of Bartter syndrome, can be associated due to several electrolyte imbalances involved in this condition. Genetic testing is essential for identifying unidentified pathogenic variants that will aid future patients diagnosed with this condition. Genetic counseling is of the utmost importance for these families affected by the condition in question.