UNASSIGNED: Imperforate hymen is an uncommon obstructive anomaly of the developing female reproductive tract. There are occasional case reports of imperforate hymen occurring in family clusters, suggesting a plausible familial mode of inheritance. We describe a set of monozygotic premature twins with imperforate hymen noted at birth, whose mother was diagnosed with the same condition as a teenager. We also elucidate the likely underlying mode of inheritance of imperforate hymen.
UNASSIGNED: We utilized the CARE (Case Report) guideline in reporting the cases.
UNASSIGNED: These are monozygotic twins born prematurely at 30 weeks of gestation, noted at birth to have bulging cyst-like structures protruding from their vaginas. The twins were not dysmorphic and did not have any other congenital malformations. Over the next few weeks, these cyst-like structures (mucoceles) became less prominent. The genital anomaly was diagnosed as imperforate hymen. Their mother was also diagnosed with an imperforate hymen when she was 12 years old and was treated with hymenectomy.
UNASSIGNED: This unique occurrence of imperforate hymen in a set of premature monozygotic twins and their mother suggests a plausible autosomal or X-linked dominant mode of inheritance. Given the role of genetic inheritance in imperforate hymen development, it is important to screen female relatives of an index case for this genital anomaly.

Palmoplantar keratoderma (PPK) is an umbrella term for a group of heterogeneous disorders, acquired or inherited, that are characterized by hyperkeratosis of palmar and/or plantar surfaces. Punctate PPK (PPPK) has been shown to have an autosomal dominant pattern of inheritance. It is linked with two loci on chromosomes 8q24.13-8q24.21 and 15q22-15q24. In type 1 PPPK, also known as Buschke-Fischer-Brauer disease, loss-of-function mutations in either the AAGAB or the COL14A1 genes have been associated with the disorder. We report here the clinical and genetic features of a patient with findings most consistent with type 1 PPPK.

The current hypothesis, along with the opinion of the breeders, is that a cat with two copies of the white spotting allele (SS) has white on more than half of its body, while a cat with only one copy (Ss) has white on less than half of its body. The present study was based on the analysis of two large pedigree databases of Siberian cats (23,905 individuals in PawPeds and 21,650 individuals in Felis Polonia database). The distribution of the amount of white spotting in the offspring of cats with different amounts of white was investigated. Significant differences compared to expected distributions were observed. In many cases the amount of white in cats that were supposed to be homozygous was less than 50% of the body, while in many supposedly heterozygous cats a very large amount of white (over 50%) was observed. This phenomenon was also presented on the verified examples of the specific families excluding possible errors in determining the amount of white by the breeder. The collected evidence suggests that there are other factors involved in the inheritance of the amount of white in cats and the current hypothesis should be revised.

Small RNAs (sRNAs) are epigenetic regulators of eukaryotic genes and transposable elements (TEs). Diverse sRNA expression patterns exist within a species, but how this diversity arises is not well understood. To provide a window into the dynamics of maize sRNA patterning, sRNA and mRNA transcriptomes were examined in two related Zea mays recombinant inbred lines (RILs) and their inbred parents. Analysis of these RILs revealed that most clusters of sRNA expression retained the parental sRNA expression level. However, expression states that differ from the parental allele were also observed, predominantly reflecting decreases in sRNA expression. When RIL sRNA expression differed from the parental allele, the new state was frequently similar between the two RILs, and similar to the expression state found at the allele in the other parent. Novel sRNA expression patterns, distinct from those of either parent, were rare. Additionally, examination of sRNA expression over TEs revealed one TE family, Gyma, which showed consistent enrichment for RIL sRNA expression differences compared to those found in parental alleles. These findings provide insights into how sRNA silencing might evolve over generations and suggest that further investigation into the molecular nature of sRNA trans regulators is warranted.

BACKGROUND: Idiopathic basal ganglia calcification (IBGC) is a neurodegenerative disease characterized by symmetrical calcification of basal ganglia and other brain region, also known as Fahr\'s disease. It can be sporadic or familial, and there is no definite etiology at present. With the development of neuroimaging, the number of reports of IBGC has increased in recent years. However, due to its hidden onset, diverse clinical manifestations, and low incidence, it is likely to be misdiagnosed or ignored by potential patients and their family.
METHODS: We report a case of a 61-year-old man who presented with symptoms of dysphagia and alalia. His computed tomography scan of the brain revealed bilateral symmetric calcifications of basal ganglia, cerebellum, thalamus, and periventricular area. The genetic test showed a new mutation sites of MYORG, c.1438T>G mutation and c.1271_1272 TGGTGCGC insertion mutation. He was finally diagnosed with IBGC.
CONCLUSIONS: It is important to detect MYORG mutation when IBGC is suspected, especially in those without an obvious family history, for better understanding of the underlying mechanism and identifying potential treatments.

Renal maldevelopment (RM) has been proposed to replace the old and sometimes misused term \"renal dysplasia\" in dogs. Although renal dysplasia has been described in Boxers, hereditary transmission has only been hypothesized. This study reports clinical and renal histological findings in Boxer dogs with RM, proposing a possible mode of inheritance. Medical records of 9 female Boxer dogs, older than 5 months and with a clinical diagnosis of chronic kidney disease prior to one year of age, were retrospectively reviewed. Polyuria and polydipsia (PU/PD), decreased appetite, weight loss, lethargy and weakness were described in all affected dogs. Common laboratory findings were proteinuria, diluted urine, non-regenerative anemia, azotemia, hyperphosphatemia, hypoalbuminemia and hypercholesterolemia. Histopathology of the kidneys revealed the presence of immature glomeruli in all dogs, which is consistent with RM. In 7 related dogs, the pedigree analysis showed that a simple autosomal recessive trait may be a possible mode of inheritance. Renal maldevelopment should be suspected in young Boxer dogs with a history of PU/PD, decreased appetite, weight loss, lethargy, weakness and proteinuria. Due to its possible inheritance, an early diagnosis of RM may allow clinicians to promptly identify other potentially affected dogs among the relatives of the diagnosed case.

Loci associated with longevity are likely to harbor genes coding for key players of molecular pathways involved in a lifelong decreased mortality and decreased/compressed morbidity. However, identifying such loci is challenging. One of the most plausible reasons is the uncertainty in defining long-lived cases with the heritable longevity trait among long-living phenocopies. To avoid phenocopies, family selection scores have been constructed, but these have not yet been adopted as state of the art in longevity research. Here, we aim to identify individuals with the heritable longevity trait by using current insights and a novel family score based on these insights. We use a unique dataset connecting living study participants to their deceased ancestors covering 37,825 persons from 1,326 five-generational families, living between 1788 and 2019. Our main finding suggests that longevity is transmitted for at least two subsequent generations only when at least 20% of all relatives are long-lived. This proves the importance of family data to avoid phenocopies in genetic studies.

Maturity onset diabetes of the young (MODY) accounts for up to 4% of all cases of diabetes in pediatric patients. MODY is usually characterized by autosomal dominant inheritance, impaired insulin secretion, and an average age at diagnosis of 18-26 years. Mutations in the hepatocyte nuclear factor 1-alpha (HNF1A), glucokinase, hepatocyte nuclear factor 4-alpha, and hepatocyte nuclear factor 1-beta genes are the mutations most frequently observed in cases of MODY. We herein report a case of HNF1A-MODY characterized by an early onset of diabetes. Genetic investigations revealed a de novo heterozygous substitution, N237D (HNF1A c.709A>G), in exon 3 of the HNF1A gene. Our case supports the hypothesis that de novo mutations are more frequent than expected. This recent evidence may suggest that conventional clinical diagnostic criteria for MODY should be revised and personalized according to the individual patient.

BACKGROUND: Rubinstein-Taybi syndrome (RSTS; OMIM #180849, #613684) is a rare autosomal dominant genetic condition characterized by broad thumbs and halluces, facial dysmorphism, short stature and variable degree of intellectual disability. RSTS is associated with mutations in CREBBP and EP300 genes in 50-60% and 5-8% of cases, respectively. The majority of cases are de novo heterozygous mutations.
METHODS: Here we describe a familial RSTS case, associated with a novel EP300 mutation. The proband was a 9 years old female, with mild learning difficulties. Her mother, who also had learning difficulties, was found to have short and broad thumbs. MLPA and panel-based NGS of CREBBP and EP300 were performed. A novel heterozygous frameshift mutation in exon 31 of the EP300 gene (c.7222_7223del; p.(Gln2408Glufs*39)) was found in both.
CONCLUSIONS: This case represents the first case of inherited EP300-RSTS. The location of the frameshift deletion not affecting HAT domain and PHD finger, could explain the mild phenotype and the well-preserved intelligence. These patients are mildly affected, and this case highlights the possible missed diagnosis. We would recommend molecular testing of apparently healthy parents, and in the case of inherited mutations, of all adult first degree relatives at risk.

Epistasis plays a significant role in the genetic architecture of many complex phenotypes in model organisms. To date, there have been very few interactions replicated in human studies due in part to the multiple-hypothesis burden implicit in genome-wide tests of epistasis. Therefore, it is of paramount importance to develop the most powerful tests possible for detecting interactions. In this work we develop a new SNP-SNP interaction test for use in case-only trio studies called the trio correlation (TC) test. The TC test computes the expected joint distribution of marker pairs in offspring conditional on parental genotypes. This distribution is then incorporated into a standard 1 d.f. correlation test of interaction. We show via extensive simulations under a variety of disease models that our test substantially outperforms existing tests of interaction in case-only trio studies. We also demonstrate a bias in a previous case-only trio interaction test and identify its origin. Finally, we show that a previously proposed permutation scheme in trio studies mitigates the known biases of case-only tests in the presence of population stratification. We conclude that the TC test shows improved power to identify interactions in existing, as well as emerging, trio association studies. The method is publicly available at www.github.com/BrunildaBalliu/TrioEpi.