Predictors of language proficiency in school-age Spanish-English bilingual children with and without developmental language disorder.

Children with developmental language disorder (DLD) have impairments in their language-learning abilities that may influence interactions with environmental opportunities to learn two languages. This study explores relationships between proficiency in L1 and L2 and a set of environmental and personal variables within a group of school-age Spanish-English bilingual children with DLD and a group of typically-developing peers. Within each group, current usage in the home, length of L2 exposure, gender, maternal education, analytical reasoning, and number of L1 conversational partners were used to predict proficiency in each language.

Biallelic KIF24 Variants Are Responsible for a Spectrum of Skeletal Disorders Ranging From Lethal Skeletal Ciliopathy to Severe Acromesomelic Dysplasia.

Skeletal dysplasias comprise a large spectrum of mostly monogenic disorders affecting bone growth, patterning, and homeostasis, and ranging in severity from lethal to mild phenotypes. This study aimed to underpin the genetic cause of skeletal dysplasia in three unrelated families with variable skeletal manifestations. The six affected individuals from three families had severe short stature with extreme shortening of forelimbs, short long-bones, and metatarsals, and brachydactyly (family 1); mild short stature, platyspondyly, and metaphyseal irregularities (family 2); or a prenatally lethal skeletal dysplasia with kidney features suggestive of a ciliopathy (family 3).

The Rac-GAP alpha2-Chimaerin Signals via CRMP2 and Stathmins in the Development of the Ocular Motor System.

A precise sequence of axon guidance events is required for the development of the ocular motor system. Three cranial nerves grow toward, and connect with, six extraocular muscles in a stereotyped pattern, to control eye movements. The signaling protein alpha2-chimaerin (α2-CHN) plays a pivotal role in the formation of the ocular motor system; mutations in , encoding α2-CHN, cause the human eye movement disorder Duane Retraction Syndrome (DRS).

KIF14 controls ciliogenesis via regulation of Aurora A and is important for Hedgehog signaling.

Primary cilia play critical roles in development and disease. Their assembly and disassembly are tightly coupled to cell cycle progression. Here, we present data identifying KIF14 as a regulator of cilia formation and Hedgehog (HH) signaling.

Cilia in hereditary cerebral anomalies.

Ciliopathies are complex genetic multi-system disorders causally related to abnormal assembly or function of motile or non-motile cilia. While most human cells possess a non-motile sensory/primary cilium (PC) during development and/or in adult tissues, motile cilia are restricted to specialised cells. As a result, PC-associated ciliopathies are characterised by high phenotypic variability with extensive clinical and genetic overlaps.

Ciliary kinesins beyond IFT: Cilium length, disassembly, cargo transport and signalling.

Cilia and flagella are microtubule-based antenna which are highly conserved among eukaryotes. In vertebrates, primary and motile cilia have evolved to exert several key functions during development and tissue homoeostasis. Ciliary dysfunction in humans causes a highly heterogeneous group of diseases called ciliopathies, a class of genetic multisystemic disorders primarily affecting kidney, skeleton, retina, lung and the central nervous system.

Loss-of-function mutations in KIF14 cause severe microcephaly and kidney development defects in humans and zebrafish.

Mutations in KIF14 have previously been associated with either severe, isolated or syndromic microcephaly with renal hypodysplasia (RHD). Syndromic microcephaly-RHD was strongly reminiscent of clinical ciliopathies, relating to defects of the primary cilium, a signalling organelle present on the surface of many quiescent cells. KIF14 encodes a mitotic kinesin, which plays a key role at the midbody during cytokinesis and has not previously been shown to be involved in cilia-related functions.

Recurrent RTTN mutation leading to severe microcephaly, polymicrogyria and growth restriction.

Autosomal recessive missense Rotatin (RTTN) mutations are responsible for syndromic forms of malformation of cortical development, ranging from isolated polymicrogyria to microcephaly associated with primordial dwarfism and other major malformations. We identified, by trio based whole exome sequencing, a homozygous missense mutation in the RTTN gene (c.2953A > G; p.

TLE1, a key player in neurogenesis, a new candidate gene for autosomal recessive postnatal microcephaly.

Postnatal microcephaly comprises a heterogeneous group of neurodevelopmental disorders of varying severity, characterized by normal head size at birth, followed by a postnatal deceleration in head circumference of greater than 3 standard deviations (SD) below the mean. Many postnatal microcephaly syndromes are caused by mutations in genes known to be important for the regulation of gene expression in the developing forebrain. We studied a consanguineous Pakistani family with postnatal microcephaly, orofacial dyskinesia, spastic quadriplegia and, on MRI, cortical atrophy with myelination delay, suggestive of a FOXG1-like presentation.

Spatiotemporally regulated proteolysis to dissect the role of vegetative proteins during Bacillus subtilis sporulation: cell-specific requirement of σ and σ.

Sporulation in Bacillus subtilis is a paradigm of bacterial development, which involves the interaction between a larger mother cell and a smaller forespore. The mother cell and the forespore activate different genetic programs, leading to the production of sporulation-specific proteins. A critical gap in our understanding of sporulation is how vegetative proteins, made before sporulation initiation, contribute to spore formation.

Functional characterization of tektin-1 in motile cilia and evidence for TEKT1 as a new candidate gene for motile ciliopathies.

A child presenting with Mainzer-Saldino syndrome (MZSDS), characterized by renal, retinal and skeletal involvements, was also diagnosed with lung infections and airway ciliary dyskinesia. These manifestations suggested dysfunction of both primary and motile cilia, respectively. Targeted exome sequencing identified biallelic mutations in WDR19, encoding an IFT-A subunit previously associated with MZSDS-related chondrodysplasia, Jeune asphyxiating thoracic dysplasia and cranioectodermal dysplasia, linked to primary cilia dysfunction, and in TEKT1 which encodes tektin-1 an uncharacterized member of the tektin family, mutations of which may cause ciliary dyskinesia.

Ciliogenesis and cell cycle alterations contribute to KIF2A-related malformations of cortical development.

Genetic findings reported by our group and others showed that de novo missense variants in the KIF2A gene underlie malformations of brain development called pachygyria and microcephaly. Though KIF2A is known as member of the Kinesin-13 family involved in the regulation of microtubule end dynamics through its ATP dependent MT-depolymerase activity, how KIF2A variants lead to brain malformations is still largely unknown. Using cellular and in utero electroporation approaches, we show here that KIF2A disease-causing variants disrupts projection neuron positioning and interneuron migration, as well as progenitors proliferation.

Targeted Exome Sequencing Identifies as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary Tract.

Congenital anomalies of the kidney and urinary tract (CAKUT) occur in three to six of 1000 live births, represent about 20% of the prenatally detected anomalies, and constitute the main cause of CKD in children. These disorders are phenotypically and genetically heterogeneous. Monogenic causes of CAKUT in humans and mice have been identified.