Biallelic KITLG variants lead to a distinct spectrum of hypomelanosis and sensorineural hearing loss

BACKGROUND: Pathogenic variants in KITLG, a crucial protein involved in pigmentation and neural crest cell migration, cause non-syndromic hearing loss, Waardenburg syndrome type 2, familial progressive hyperpigmentation and familial progressive hyper- and hypopigmentation, all of which are inherited in an autosomal dominant manner. OBJECTIVES: To describe the genotypic and clinical spectrum of biallelic KITLG-variants. METHODS: We used a genotype-first approach through the GeneMatcher data sharing platform to collect individuals with biallelic KITLG variants and reviewed the literature for overlapping reports. RESULTS: We describe the first case series with biallelic KITLG variants; we expand the known hypomelanosis spectrum to include a 'sock-and-glove-like', symmetric distribution, progressive repigmentation and generalized hypomelanosis. We speculate that KITLG biallelic loss-of-function variants cause generalized hypomelanosis, whilst variants with residual function lead to a variable auditory-pigmentary disorder mostly reminiscent of Waardenburg syndrome type 2 or piebaldism. CONCLUSIONS: We provide consolidating evidence that biallelic KITLG variants cause a distinct auditory-pigmentary disorder. We evidence a significant clinical variability, similar to the one previously observed in KIT-related piebaldism

Identifying Consensus Disease Pathways in Parkinson's Disease Using an Integrative Systems Biology Approach

Parkinson's disease (PD) has had six genome-wide association studies (GWAS) conducted as well as several gene expression studies. However, only variants in MAPT and SNCA have been consistently replicated. To improve the utility of these approaches, we applied pathway analyses integrating both GWAS and gene expression. The top 5000 SNPs (p<0.01) from a joint analysis of three existing PD GWAS were identified and each assigned to a gene. For gene expression, rather than the traditional comparison of one anatomical region between sets of patients and controls, we identified differentially expressed genes between adjacent Braak regions in each individual and adjusted using average control expression profiles. Over-represented pathways were calculated using a hyper-geometric statistical comparison. An integrated, systems meta-analysis of the over-represented pathways combined the expression and GWAS results using a Fisher's combined probability test. Four of the top seven pathways from each approach were identical. The top three pathways in the meta-analysis, with their corrected p-values, were axonal guidance (p = 2.8E-07), focal adhesion (p = 7.7E-06) and calcium signaling (p = 2.9E-05). These results support that a systems biology (pathway) approach will provide additional insight into the genetic etiology of PD and that these pathways have both biological and statistical support to be important in PD

Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort

Purpose:Autosomal recessive nonsyndromic deafness (ARNSD) is characterized by a high degree of genetic heterogeneity, with reported mutations in 58 different genes. This study was designed to detect deafness-causing variants in a multiethnic cohort with ARNSD by using whole-exome sequencing (WES).Methods:After excluding mutations in the most common gene, GJB2, we performed WES in 160 multiplex families with ARNSD from Turkey, Iran, Mexico, Ecuador, and Puerto Rico to screen for mutations in all known ARNSD genes.Results:We detected ARNSD-causing variants in 90 (56) families, 54 of which had not been previously reported. Identified mutations were located in 31 known ARNSD genes. The most common genes with mutations were MYO15A (13), MYO7A (11), SLC26A4 (10), TMPRSS3 (9), TMC1 (8), ILDR1 (6), and CDH23 (4). Nine mutations were detected in multiple families with shared haplotypes, suggesting founder effects.Conclusion:We report on a large multiethnic cohort with ARNSD in which comprehensive analysis of all known ARNSD genes identifies causative DNA variants in 56 of the families. In the remaining families, WES allows us to search for causative variants in novel genes, thus improving our ability to explain the underlying etiology in more families.Genet Med 18 4, 364-371. © American College of Medical Genetics and Genomics

First illustrations of female "Neurosurgeons" in the fifteenth century by Serefeddin

Los hombres han dominado la medicina durante muchos siglos. Las mujeres no aparecen en la historia de la medicina hasta el final del siglo XVIII, aunque siempre han estado en la medicina como curanderas. Vale la pena mencionar que las primeras ilustraciones que indican la presencia de mujeres en la cirugía se encontraron en un libro escrito en turco por Serefeddin Sabuncuoglu en el siglo XV, mientras Europa todavía despertaba de la oscuridad y el Oriente Medio estaba bajo la influencia de las estrictas reglas de la cultura Arábiga e Islámica. Serefeddin Sabuncuoglu (1385- 1470) fue el autor del primer texto quirúrgico ilustrado Cerrahiyyetu'l-Haniyye (Cirugía Imperial) en Literatura Turca. Las miniaturas dibujadas por Sereffeddin Sabuncuoglu indicaban que las mujeres cirujanos, conocidas como "Tabibe", estaban autorizadas para practicar sólo en Anatolia. Se ilustra, en miniaturas, cómo las Tabibes actuaban en el tratamiento de fetos muertos con hidrocefalia y macrocefalia que fueron, por supuesto, los primeros datos de mujeres turcas en la Neurocirugía

First illustrations of female "Neurosurgeons" in the fifteenth century by Serefeddin Sabuncuoglu

WOS: 000238561100015PubMed: 16721484Males have dominated medicine for many centuries. Females could not appear in the medical history equally till the end of the 18(th) century; although they always have been in medicine as healers. It is worth mentioning that first illustrations indicating female surgeons were found in the book written in Turkish by Serefeddin Sabuncuoglu in the 15(th) century; while Europe was newly waking up from its dark ages and Middle East was under the influence of strict rules of Arabic and Islamic culture. Serefeddin Sabuncuoglu (1385-1470) was the author of the first illustrated surgical textbook Cerrahiyyetu'l-Haniyye (Imperial surgery) in Turkish Literature

Postoperative spinal ultrasonography findings in spinal dysraphia

PubMed: 16206054Diastematomyelia is a form of spinal dysraphism involving sagittal clefting of the spinal cord, conus medullaris, and/or filum terminale into two hemicords. It can be an isolated finding or can be associated with meningomyelocele or meningocele. In this report, we present postoperative spinal ultrasonography findings in a patient with diastematomyelia and a tethered cord. © Turkish Society of Radiology 2005

Paranazal sinüslerle nörovasküler yapilarin bağlantisinin cerrahi önemi

Objective: Damage to the optic nerve and internal carotid artery is a serious complication of transsphenoidal surgery. The relationships of the sphenoid sinuses to the carotid artery and optic nerve were studied on computerized tomography and their clinical importance was discussed. Methods: 45 (90 sides) paranasal tomography images consisting of coronal, axial or both coronal and axial images were evaluated. Tomographic findings including bony septum extending to the optic canal or internal carotid artery and protrusions and dehiscences of the walls of the internal carotid artery and the optic nerve were investigated. The results were classified as "present" or "absent". Results: We detected 28 protrusions and 4 dehiscences of internal carotid artery and 31 protrusions and 7 dehiscences of the optic nerve. Bony septum to the internal carotid artery and optic nerve was observed in 25 and 18 cases respectively. Conclusion: Detailed preoperative analysis of the anatomy of the sphenoid sinus and its neurovascular boundaries is crucial in facilitating entry to the pituitary fossa and reducing intraoperative complications. Axial and coronal images, or axialcoronal investigation obtained by direct acquisition or by reconstructions are necessary to show the positions and variations of the optic nerve and carotid artery

Faun Tail: Diagnosis of Occult Spinal Dysraphism with a Rare Cutaneous Marker [4]

PubMed: 15187350[No abstract available

"Triple cross" of the hypoglossal nerve and its microsurgical impact to entrapment disorders

WOS: 000241635400010PubMed: 17041836Objective: Cadaveric dissections were performed to review the intracranial and extracranial course of the hypoglossal nerve. The neurological significance of a newly defined "triple cross" of the hypoglossal nerve is discussed. Materials and Methods: 10 cadaveric heads (left and right; 20 sides) were dissected using microsurgical techniques. Results: In the cisternal segment of hypoglossal nerve, the diameter of the rostral trunk amounted to 155-680 mu m (mean 435 mu m), and the caudal trunk to 210-820 mu m (mean 482 mu m). The roots formed three trunks in 20% of the hypoglossal nerves and two trunks in the rest. As a first cross, the anterior medullary segment of the vertebral artery crossed the hypoglossal nerve roots in 14 of 20 sides (70%). As a rare variation, the vertebral artery extended medial to the nerve (25%) or between its roots (5%). The second cross was found between the descendens hypoglossus and the occipital artery (75%), sternocleidomastoid artery and vein complex (15%) and external carotid artery (10%). The third cross was shown in the submandibular triangle between the lingual hypoglossus and its drainage vein; vena committans nervus hypoglossus. Conclusion: Throughout its way, the hypoglossal nerve passes over vascular structures in three crossing points which may serve as a probable cause of hypoglossal nerve entrapment disorders

Persistent metopic suture can mimic the skull fractures in the emergency setting?

WOS: 000248997400009PubMed: 17622463Metopism is partially or totally persisting suture extending from the nasion to the anterior angle of the bregma. The time of physiological closure of the metopic suture varies from birth to 8 years of age. Widely accepted closuring time is approximated at 2 years of age. Although formerly reported skull studies mentioned the persistent metopic suture, it is extremely rare in clinical practice. We presented a trauma case of 43 years of age who was demonstrated radiologically to have a persisting suture. Persistent metopic suture may be misdiagnosed as a vertical traumatic skull fracture extending in the mid-line in head trauma patients. Therefore the surgeon should be aware of this anatomical condition in the primary and secondary surveillance of the traumatized patient and during surgical intervention including especially frontal craniotomy. Reconstructed tomography scan demonstrating sutural closuring status may provide additional informative value in the diagnostic sequence superior to plain X-ray in the emergency setting