Expanding the clinical spectrum of biglycan-related Meester-Loeys syndrome.

Pathogenic loss-of-function variants in BGN, an X-linked gene encoding biglycan, are associated with Meester-Loeys syndrome (MRLS), a thoracic aortic aneurysm/dissection syndrome. Since the initial publication of five probands in 2017, we have considerably expanded our MRLS cohort to a total of 18 probands (16 males and 2 females). Segregation analyses identified 36 additional BGN variant-harboring family members (9 males and 27 females).

A familial missense variant in the Alzheimer's disease gene SORL1 impairs its maturation and endosomal sorting.

The SORL1 gene has recently emerged as a strong Alzheimer's Disease (AD) risk gene. Over 500 different variants have been identified in the gene and the contribution of individual variants to AD development and progression is still largely unknown. Here, we describe a family consisting of 2 parents and 5 offspring.

NOTCH3 C201R variant causes cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) that can be confused with early-onset Alzheimer's disease.

Background: NOTCH3 is the causative gene for autosomal dominant cerebral arteriopathy with subcortical infarctions and leukoencephalopathy (CADASIL) which is associated with both stroke and dementia. When CADASIL presents primarily as dementia it can be difficult to distinguish from Alzheimer's disease (AD) at both the clinical and neuropathological levels.

Methods: We performed exome sequencing of several affected individuals from a large family affected with AD.

A familial missense variant in the Alzheimer's Disease gene impairs its maturation and endosomal sorting.

The gene has recently emerged as a strong Alzheimer's Disease (AD) risk gene. Over 500 different variants have been identified in the gene and the contribution of individual variants to AD development and progression is still largely unknown. Here, we describe a family consisting of 2 parents and 5 offspring.

Novel LMNA mutations in Greek and Myanmar Patients with Progeroid Features and Cardiac Manifestations.

Segmental progeroid syndromes are groups of genetic disorders with multiple features resembling accelerated aging. The International Registry of Werner Syndrome (Seattle, WA) recruits pedigrees of progeroid syndromes from all over the world. We identified two novel LMNA mutations, p.

Alternative splicing in a presenilin 2 variant associated with Alzheimer disease.

Objective: Autosomal-dominant familial Alzheimer disease (AD) is caused by by variants in presenilin 1 (), presenilin 2 (), and amyloid precursor protein (). Previously, we reported a rare frameshift variant in an early-onset AD case (PSEN2 p.K115Efs*11).

Characterization of Adult Vestibular Organs in 11 CreER Mouse Lines.

Utricles are vestibular sense organs that encode linear head movements. They are composed of a sensory epithelium with type I and type II hair cells and supporting cells, sitting atop connective tissue, through which vestibular nerves project. We characterized utricular Cre expression in 11 murine CreER lines using the ROSA26 reporter line and tamoxifen induction at 6 weeks of age.

Supporting cells remove and replace sensory receptor hair cells in a balance organ of adult mice.

Vestibular hair cells in the inner ear encode head movements and mediate the sense of balance. These cells undergo cell death and replacement (turnover) throughout life in non-mammalian vertebrates. However, there is no definitive evidence that this process occurs in mammals.