Nubbins Research Articles

Identification of Goat Supernumerary Teat Phenotype Using Wide-Genomic Copy Number Variants

Supernumerary teats (SNTs) or nipples often emerge around the mammary line. This study performed a genome-wide selective sweep analysis (GWS) at the copy number variant (CNV) level using two selected signal calculation methods (VST and FST) to identify candidate genes associated with SNTs in goats. A total of 12,310 CNVs were identified from 37 animals and 123 CNVs, with the top 1% VST values including 84 candidate genes (CDGs). Of these CDGs, minichromosome maintenance complex component 3, ectodysplasin A receptor associated via death domain, and cullin 5 demonstrated functions closely related to mammary gland development. In addition, 123 CNVs with the top 1% FST values were annotated to 97 CDGs. 5-Hydroxytryptamine receptor 2A, CCAAT/enhancer-binding protein alpha, and the polymeric immunoglobulin receptor affect colostrum secretion through multiple signaling pathways. Two genes, namely, RNA-binding motif protein 46 and β-1,3-galactosyltransferase 5, showed a close relation to mammary gland development. Six CNVs were identified and annotated to five genes by intersecting the top 1% of candidate CNVs with both parameters. These genes include LOC102185621, LOC102190481, and UDP-glucose pyrophosphorylase 2, which potentially affect the occurrence of BC through multiple biological processes, such as cell detoxification, glycogen synthesis, and phospholipid metabolism. In conclusion, we discovered numerous genes related to mammary development and breast cancer (BC) through a GWS, which suggests the mechanism of SNTs in goats and a certain association between mammary cancer and SNTs.

Accessory breast tissue-A matter for exigence!

The accessory breast tissue is found in 6%. It is seen commonly in the axilla. It is asymptomatic or causes pain, restricts arm movement, causes cosmetic problems, or causes anxiety. We evaluated symptoms, signs, investigations, treatment, and postoperative complications of women with accessory breast tissue. Our cross-sectional study was conducted in the Surgery OPD, Nagpur, on 52 women who presented with accessory breast tissue in the period from January 2019 to October 2023. In this study, of 52 patients, the majority, that is, 38 (73.07%) patients, presented with uneasiness due to the position of mass followed by 25 (48.07%) with swelling in the axilla. Twelve (23.07%) patients presented with pain in mass in premenstrual and menstrual periods, and seven (13.46%) patients with accessory nipples. Fifty (96.15%) patients had axillary swelling. One (1.92%) patient each had swelling in groin and thigh. Thirty-six (69.2%) patients had sonography findings consistent with breast-like tissue. In nine (17.30%) patients, findings suggested lipoma. Surgical excision was conducted in 52 (100%) patients. In 43 (82.69%) patients, histopathology was consistent with simple breast tissue. In six (11.53%) patients, it was fibroadenoma, and in three (6.76%) patients, histopathology was suggestive of carcinoma. Twenty-eight (53.84%) patients had no complications. Thirteen (25%) patients had an allergy to sticking, six (11.53%) patients had uneven scar, and four (7.69%) patients had hypertrophy of scar. In our study, in the majority of patients, the site of accessory breast tissue was axilla. It caused uneasiness. Surgical excision was conducted in all patients. Postoperative complications were the least.

Observations of Weddell seal (Leptonychotes weddellii) supernumerary nipples

A wide variety of nipple locations and configurations exist among pinnipeds. Like all marine mammals, pinnipeds can have supernumerary nipples that form in utero. Supernumerary nipples have been documented in several species of pinnipeds, the only taxonomic group of marine mammals with variation in nipple number. We document multiple observations (n = 4) of female Weddell seals (Leptonychotes weddellii) with supernumerary nipples in Erebus Bay, Antarctica, including a female Weddell seal with four nipples that was observed nursing two pups. Intraspecific variation in the number of supernumerary nipples observed included both one and two supernumerary nipples. The majority of the observed supernumerary nipples were nursed on by pups, but lactation was unable to be confirmed. These are the first documented observations of supernumerary nipples in Weddell seals.

Treatment Options for the Clinical Management of Axillary Breast Tissue.

Axillary breast tissue includes any combination of fat, nipple, areolae, and glandular tissue alongside breasts and affects 2%-6% of women and 1%-3% of men. Patients may experience functional and/or cosmetic concerns due to axillary breast tissue. There are nonsurgical options for its removal, such as CoolSculpting and Kybella, and surgical options such as liposuction, BodyTite liposuction, and excision. Determining which technique to use in each case is critical in achieving an excellent outcome. Currently, there are no established treatment algorithms for the removal of axillary breast tissue. A retrospective review between January 1, 2013, and June 20, 2022, was performed. Data that were extracted included age, BMI, date of procedure, procedure, fat suctioned, tissue excised, and follow-up period. The authors analyzed outcomes and formulated a treatment algorithm based on tissue type (fat versus glandular), amount of tissue excess, skin laxity, and accessory nipple presence. A total of 43 patients (83 axillae) met our inclusion criteria and were included in our analysis. All patients were female with a mean age of 35.5 ± 10.9 years, a mean BMI of 23.0 ± 3.1, and a mean follow-up period of 8.8 ± 11.1 months. For inclusion, patients had to have undergone CoolSculpting, liposuction, BodyTite liposuction, liposuction with excision, or excision alone. All patients tolerated the procedures well and reported no serious complications. Nonsurgical and surgical removal of axillary breast tissue is safe and effective. The algorithm presented can be utilized by plastic and reconstructive surgeons to ensure optimal results for axillary breast tissue removal.

Schwannoma: Another dermoscopic pitfall?

Schwannoma: Another dermoscopic pitfall?

Somatic mosaicism in STAG2-associated cohesinopathies: Expansion of the genotypic and phenotypic spectrum.

STAG2 is a component of the large, evolutionarily highly conserved cohesin complex, which has been linked to various cellular processes like genome organization, DNA replication, gene expression, heterochromatin formation, sister chromatid cohesion, and DNA repair. A wide spectrum of germline variants in genes encoding subunits or regulators of the cohesin complex have previously been identified to cause distinct but phenotypically overlapping multisystem developmental disorders belonging to the group of cohesinopathies. Pathogenic variants in STAG2 have rarely been implicated in an X-linked cohesinopathy associated with undergrowth, developmental delay, and dysmorphic features. Here, we describe for the first time a mosaic STAG2 variant in an individual with developmental delay, microcephaly, and hemihypotrophy of the right side. We characterized the grade of mosaicism by deep sequencing analysis on DNA extracted from EDTA blood, urine and buccal swabs. Furthermore, we report an additional female with a novel de novo splice variant in STAG2. Interestingly, both individuals show supernumerary nipples, a feature that has not been reported associated to STAG2 before. Remarkably, additional analysis of STAG2 transcripts in both individuals showed only wildtype transcripts, even after blockage of nonsense-mediated decay using puromycin in blood lymphocytes. As the phenotype of STAG2-associated cohesinopathies is dominated by global developmental delay, severe microcephaly, and brain abnormalities, we investigated the expression of STAG2 and other related components of the cohesin complex during Bioengineered Neuronal Organoids (BENOs) generation by RNA sequencing. Interestingly, we observed a prominent expression of STAG2, especially between culture days 0 and 15, indicating an essential function of STAG2 in early brain development. In summary, we expand the genotypic and phenotypic spectrum of STAG2-associated cohesinopathies and show that BENOs represent a promising model to gain further insights into the critical role of STAG2 in the complex process of nervous system development.

Simpson-Golabi-Behmel Syndrome: A Case Report

Simpson-Golabi-Behmel syndrome (GBS) is a rare, X-linked recessive genetic disorder caused by loss-of-function mutations in the GPC3 (Xq26) gene, with polymorphic clinical presentation and evolutionary profile, characterized by growth accelerated pre- and postnatal, facial dysmorphism and visceral and skeletal malformations, varied and inconstant, as well as an increased tumor risk. We report the case of a 4-month-old infant, the result of a poorly followed pregnancy carried to term, birth weight was 4200g with notion of delayed cry. The parents are non-consanguineous, no similar case in the family. Our patient is followed for hemicorporal tonic-clonic epileptic seizures evolving since birth, controlled by phenobarbital. Clinical examination found psychomotor retardation, height and weight advance, macrocrania, enlarged anterior fontanelle, facial dysmorphism with hypertelorism and obliterated nasal root, supernumerary nipple, umbilical hernia and polydactyly. Examination of the external genitalia reveals cryptorchidism bilateral. A paraclinical assessment was requested to look for associated malformations came back normal. In the light of the literature and through this observation, the authors support the phenotypic, genetic and evolutionary particularities of the syndrome by Simpson-Golabi-Behmel.

Spondylocostal dysplasia: a rare cause of respiratory distress in term neonates

Jarcho-Levin syndrome (JLS) also known as spondylocostal dysplasia is a rare congenital dysplastic disorder involving ribs and vertebrae. It as an autosomal recessive form of inheritance however dominant forms have also been reported. Multiple genes have been postulated to be causative, however exact genetic basis is not known. Infants usually present at birth with respiratory distress and have varying degree of thoracic and vertebral anomalies. We present a case of term male infant with a clinical diagnosis of JLS. The infant presented at birth with distress with no significant antenatal risk factors. On examination he was found to have a short neck, short trunk, accessory nipple with asymmetrical chest wall. X-ray suggested absent ribs (2-8) on left side with hemivertebrae (T3-T8). The baby was managed conservatively and is being followed up with neonatologists, orthopaedicians and pediatric surgeons.

SIMPSON-GOLABI-BEHMEL syndrome type 1: How placental immunohistochemistry can rapidly Predict the diagnosis

IntroductionGlypican-3 (GPC3) is an oncofetal protein involved in cellular signaling, strongly expressed in the placenta, absent or diminished in postnatal life, but often increased in human malignancies. Germline loss-of-function variants of GPC3 gene are associated with Simpson-Golabi-Behmel syndrome type 1 (SGBS1), a rare recessive X-linked overgrowth disease characterized by typical facial features, congenital abnormalities, and an increased risk of developing childhood cancers. MethodsA clinical suspicion of SGBS1 was postulated for a newborn with prenatal history of overgrowth and polyhydramnios, presenting with neonatal weight and length >99th percentile, coarse facies, iris and retinal coloboma, supernumerary nipples, and splenomegaly. While waiting for whole-genome sequencing (WGS) results, we investigated placental GPC3 immunohistochemical expression in the proband, in three additional cases of SGBS1, and disorders commonly associated with fetal macrosomia and/or placentomegaly. ResultsWGS in the proband identified a likely pathogenic maternally inherited missense variant in GPC3: c.1645A > G, (p.Ile549Val), and GPC3 immunohistochemistry demonstrated full-thickness loss of stain of the placental parenchyma. The same pattern (“null”) was also present in the placentas of three additional cases of SGBS1, but not in those of unaffected controls. DiscussionImmunohistochemical expression of GPC3 in the placenta is highly reproducible. Our findings showed that a “null pattern” of staining is predictive of SGBS1 and represents a valuable aid in the differential diagnosis of fetal macrosomias, allowing targeted genetic testing and earlier diagnosis.

Precocious puberty in a case of Simpson–Golabi–Behmel syndrome with a de novo 240-kb deletion including GPC3

Here, we report a Japanese patient with Simpson–Golabi–Behmel syndrome involving a de novo 240-kb deletion including a part of GPC3. The patient showed pre- and postnatal macrosomia associated with coarse face, macrocephaly, supernumerary nipples, and cryptorchidism and characteristically presented with precocious puberty, mostly evaluated as advanced pubertal age of 15 years at the chronological age of 11.5 years.

Polythelia associated with hypogonadotropic hypogonadism in young male: A case report

Polythelia is a congenital anomaly in which there is a third or more nipples. Although it is a relatively rare condition, it is frequently associated with other congenital malformations including the cardiovascular, urogenital, and skeletal systems. It may occur sporadically or with a familial tendency with some genetic factors. We report an association of polythelia with congenital hypogonadotropic hypogonadism (CHH) in a young male. The patient was complaining of delayed puberty. He was short in stature and had hypogonadism. On physical examination, a third nipple was found below the normal left nipple along the left mammary line. The case was carefully evaluated to exclude other disorders. It has been suggested that every newborn can be checked for the presence of accessory nipples which could indicate another internal problem in its body. We report the association of accessory nipple and right-sided hydronephrosis in a female term newborn.

Rare Case of Fibroadenoma within Ectopic Breast Tissue in Axilla – A Case Report and Review of Literature

The congenital anomalies of breast, especially the polymastia (supernumerary breast) and polythelia (supernumerary nipple), can have varied presentations, associated renal anomalies, and pathologies arising from them. The axillary polymastia is a variant of ectopic breast tissue (EBT). Ectopic breast tissue can undergo the same physiological and pathological processes as the normally located breast. The incidence of fibroadenoma developing in ectopic breast is reported as a rare entity, the most common being the carcinoma. Here we report a case of fibroadenoma developing in ectopic breast tissue located in axilla.

Novel insights into PORCN mutations, associated phenotypes and pathophysiological aspects

BackgroundGoltz syndrome (GS) is a X-linked disorder defined by defects of mesodermal- and ectodermal-derived structures and caused by PORCN mutations. Features include striated skin-pigmentation, ocular and skeletal malformations and supernumerary or hypoplastic nipples. Generally, GS is associated with in utero lethality in males and most of the reported male patients show mosaicism (only three non-mosaic surviving males have been described so far). Also, precise descriptions of neurological deficits in GS are rare and less severe phenotypes might not only be caused by mosaicism but also by less pathogenic mutations suggesting the need of a molecular genetics and functional work-up of these rare variants.ResultsWe report two cases: one girl suffering from typical skin and skeletal abnormalities, developmental delay, microcephaly, thin corpus callosum, periventricular gliosis and drug-resistant epilepsy caused by a PORCN nonsense-mutation (c.283C > T, p.Arg95Ter). Presence of these combined neurological features indicates that CNS-vulnerability might be a guiding symptom in the diagnosis of GS patients. The other patient is a boy with a supernumerary nipple and skeletal anomalies but also, developmental delay, microcephaly, cerebral atrophy with delayed myelination and drug-resistant epilepsy as predominant features. Skin abnormalities were not observed. Genotyping revealed a novel PORCN missense-mutation (c.847G > C, p.Asp283His) absent in the Genome Aggregation Database (gnomAD) but also identified in his asymptomatic mother. Given that non-random X-chromosome inactivation was excluded in the mother, fibroblasts of the index had been analyzed for PORCN protein-abundance and -distribution, vulnerability against additional ER-stress burden as well as for protein secretion revealing changes.ConclusionsOur combined findings may suggest incomplete penetrance for the p.Asp283His variant and provide novel insights into the molecular etiology of GS by adding impaired ER-function and altered protein secretion to the list of pathophysiological processes resulting in the clinical manifestation of GS.

Two different presentations of de novo variants of CSNK2B: two case reports

BackgroundPoirier–Bienvenu neurodevelopmental syndrome is a neurologic disorder caused by mutations in the CSNK2B gene. It is mostly characterized by early-onset seizures, hypotonia, and mild dysmorphic features. Craniodigital syndrome is a recently described disorder also related to CSNK2B, with a single report in the literature.ObjectiveTo report two unrelated cases of children harboring CSNK2B variants (NM_001320.6) who presented with distinct diseases.Case reportCase 1 is a 7-month-old, Caucasian, female patient with chief complaints of severe hypotonia and drug-refractory myoclonic epilepsy, with a likely pathogenic de novo variant c.494A>G (p.His165Arg). Case 2 is a 5-year-old male, Latino patient with craniodigital intellectual disability syndrome subjacent to a de novo, likely pathogenic variant c.94G>T (p.Asp32Tyr). His dysmorphic features included facial dysmorphisms, supernumerary nipples, and left-hand postaxial polydactyly.ConclusionThis report suggest that the CSNK2B gene may be involved in the physiopathology of neurodevelopmental disorders and variable dysmorphic features.

Accessory breast cancer in the inframammary region: a case report and review of the literature

BackgroundAlthough a few cases of accessory breast cancer (ABC) have been reported, most were in the axillary region. We encountered an extremely rare case of ABC in the inframammary region (IMR).Case presentationThe patient was a 68-year-old postmenopausal woman who had noticed a congenital accessory nipple in her left IMR with slight, occasional discharge 20 years ago. Recently, she noticed a mass under the accessory nipple and visited a nearby clinic; fine-needle aspiration cytology of the mass revealed that it was malignant. She presented to our department 2 weeks after she had noticed the mass. Physical and imaging examinations showed an irregular tumor mass 1.7 × 1.4 × 1.0 cm in size connected to the accessory nipple beneath the left normal breast. Neither distant metastasis nor lymph node swelling was observed. Ultrasound-guided core needle biopsy revealed the mass to be invasive ductal carcinoma. We diagnosed her tumor as ABC in the left IMR; cT1cN0M0: stage IA. Curative wide resection with sentinel node biopsy was performed. Intraoperative evaluation of the frozen section revealed a hot and green ipsilateral axillary lymph node that was free from carcinoma; therefore, nodal dissection was avoided. Histopathological examination including immunochemical staining revealed that the tumor was invasive ductal carcinoma arising from the accessory breast tissue, scirrhous type, 1.7 × 1.4 × 1.0 cm in size, with a solid intraductal component. There was no lymphovascular infiltration, and the surgical margin was 1.5 cm or more. The tumor was estrogen and progesterone receptor-positive, Her2/neu-negative, and had a Ki-67 labeling index of 20%. There was no involvement of the three hot and/or green nodes. The final classification was pT1cN0(sn)M0: stage IA. Letrozole 2.5 mg/day will be administered for 5 years as adjuvant hormonal therapy.ConclusionsA cutaneous and/or subcutaneous lesion except for proper breast tissue on the milk line, or mammary ridge from axilla to groin may be an accessory breast tissue. Its serial abnormalities must be worried malignant potential to ductal carcinoma which needs some imaging and pathological examinations for definitive diagnosis and appropriate treatment according to the usual orthotopic breast cancer without delay.

WITHDRAWN: Bilateral axillary tumour in a 12-year-old girl: a case report

Ectopic breast tissue is a rare condition in the Caucasian population. The most frequent form is polythelia (supernumerary nipples), whereas polymastia (complete supernumerary breasts) is more uncommon. They are usually benign asymptomatic lesions that go undetected until pregnancy or lactation. However, they are under the same hormonal influence as normal breast tissue and therefore are susceptible to malignant changes. a 12-year-old girl presented bilateral axillary polymastia and polythelia, detected with puberal changes. Surgical removal was postponed until the end of puberal development. Polymastia is a rare condition that can have psychological consequences, especially in adolescents. It has been associated with other malformations and malignant tumours, so surgical removal is usually recommended.

Genome-Wide Detection of Copy Number Variations and Their Association With Distinct Phenotypes in the World's Sheep.

Copy number variations (CNVs) are a major source of structural variation in mammalian genomes. Here, we characterized the genome-wide CNV in 2059 sheep from 67 populations all over the world using the Ovine Infinium HD (600K) SNP BeadChip. We tested their associations with distinct phenotypic traits by conducting multiple independent genome-wide tests. In total, we detected 7547 unique CNVs and 18,152 CNV events in 1217 non-redundant CNV regions (CNVRs), covering 245 Mb (∼10%) of the whole sheep genome. We identified seven CNVRs with frequencies correlating to geographical origins and 107 CNVRs overlapping 53 known quantitative trait loci (QTLs). Gene ontology and pathway enrichment analyses of CNV-overlapping genes revealed their common involvement in energy metabolism, endocrine regulation, nervous system development, cell proliferation, immune, and reproduction. For the phenotypic traits, we detected significantly associated (adjusted P < 0.05) CNVRs harboring functional candidate genes, such as SBNO2 for polycerate; PPP1R11 and GABBR1 for tail weight; AKT1 for supernumerary nipple; CSRP1, WNT7B, HMX1, and FGFR3 for ear size; and NOS3 and FILIP1 in Wadi sheep; SNRPD3, KHDRBS2, and SDCCAG3 in Hu sheep; NOS3, BMP1, and SLC19A1 in Icelandic; CDK2 in Finnsheep; MICA in Romanov; and REEP4 in Texel sheep for litter size. These CNVs and associated genes are important markers for molecular breeding of sheep and other livestock species.

TBX3 and TBX5 duplication: A family with an atypical overlapping Holt-Oram/ulnar-mammary syndrome phenotype

Holt-Oram syndrome (HOS) is a rare, autosomal dominant heart-hand syndrome caused by mutations in the TBX5 gene. A wide spectrum of TBX5 mutations have been reported previously, most resulting in a null allele leading to haploinsufficiency. TBX5 gene duplications have been previously reported in association with typical and atypical HOS phenotypes. Ulnar-Mammary syndrome (UMS) is a distinct rare, autosomal dominant condition caused by mutations in the TBX3 gene. TBX5 and TBX3 are physically linked in cis on human chromosome 12 and contiguous chromosome 12q24 deletions comprising both TBX5 and TBX3 genes have been previously reported but to our knowledge, duplications have never been described. We report on a large German family with at least 17 affected individuals over 6 generations bearing a duplication at 12q24.21 identified on array-CGH comprising both TBX5 and TBX3 genes. Affected patients are presenting with HOS and UMS symptoms, consisting of variable limb anomalies involving the radial and the ulnar rays and cardiac findings such as congenital heart defects, persistent arterial duct or aortic stenosis, and non-classical symptoms, such as supernumerary nipples and cardiomyopathy. Fluorescence in situ hybridisation confirmed a tandem duplication at the 12q24.21 locus. This is the first report of a contiguous TBX3/TBX5 duplication associated with HOS/UMS phenotype.

Fetal valproate syndrome: A case report

Sodium Valproate has been used as an antiepileptic drug for a long time. It is also increasingly used for treating bipolar disorder and other affective disorders. However, it is a potential teratogen and is one of the best depicted prototypes of the harmful effects of an antiepileptic drug. The most frequent congenital malformations associated with Fetal Valproate Syndrome are neural tube defects, congenital heart diseases, and orogenital abnormalities while inguinal and umbilical hernia, supernumerary nipple, bifid ribs, preaxial defect of feet, and postaxial polydactyly are less frequent abnormalities. Here, we report two cases of Fetal Valproate Syndrome in a 3.5-year-old boy and his 7-year-old brother with dysmorphic features.

Bilateral ankyloblepharon: more than a simple malformation

“Ankyloblepharon filiforme adnatum” is a congenital anomaly characterized by partial or complete adhesion of upper and lower eyelids. The lid margins remain fused until the end of the fifth month of gestational age. Complete separation usually is completed about the seventh fetal month. Ankyloblepharon may be an isolated manifestation or may be associated with abnormalities in other organs and/or systems. The case is presented on a newborn male with family history of hypohydrotic ectodermal dysplasia (mother and maternal grandfather). It revealed extensible bands of skin in right and in left eye. Apart from this, he presented cleft lip, complete absence of palate, nail and ungueal dysplasia and supernumerary nipples. El “anquilobléfaron filiforme adnatum” es una anomalía congénita caracterizada por la adhesión parcial de los párpados superiores e inferiores. Los márgenes del párpado permanecen fusionados hasta el final del quinto mes de edad gestacional. La separación suele completarse alrededor del séptimo mes fetal. El anquilobléfaron puede ser una manifestación aislada o puede estar asociado con anomalías en otros órganos y/o sistemas. Presentamos un varón recién nacido con antecedentes familiares de displasia ectodérmica hipohidrótica (madre y abuelo materno). Se revelaron bandas extensibles de piel en el ojo derecho y en el izquierdo. Aparte de esto, presentó labio leporino, ausencia total de paladar, displasia de uñas y ungueal y pezones supernumerarios.