Identification of a rare homozygous variant due to uniparental disomy in a patient with a neurodevelopmental disorder.

Because biallelic variants have been reported in patients with neurodevelopmental disorders associated with various degrees of developmental delay, intractable seizures, and distinctive features; this condition is recognized as an autosomal recessive disorder. Previously, eleven patients have been reported and most of them have compound heterozygous variants, leading to premature termination. In these patients, all reported variants were unique and there were no common pathogenic variants identified.

Early-Onset Diabetes Mellitus in a Patient With a Chromosome 13q34qter Microdeletion Including .

Diabetes mellitus is a multifactorial disease caused by a complex interaction of environmental and genetic factors. Some diabetes mellitus cases, however, are caused by a limited number of mutant genes. Chromosome 13q deletion syndrome, an extremely rare genetic disorder, is caused by structural and functional monosomy of the 13q chromosomal region.

Infantile spasms related to a 5q31.2-q31.3 microdeletion including .

Recently, haploinsufficiency of has been identified as an essential cause of 5q31.3 microdeletion syndrome, which is characterized by severe psychomotor developmental delay, epilepsy, distinctive features, and delayed myelination. A new 5q31.

Novel and recurrent variants in Japanese pediatric patients with moyamoya disease.

Moyamoya disease is a progressive steno-occlusive condition of the main intracranial arteries that results in the compensatory formation of fragile moyamoya vessels at the base of the brain. is the most significant susceptibility gene and is often found with the p.Arg4810Lys founder variant in East Asian patients.

Somatic mosaic deletions involving SCN1A cause Dravet syndrome.

Somatic mosaicism in single nucleotide variants of SCN1A is known to occur in a subset of parents of children with Dravet syndrome (DS). Here, we report recurrent somatic mosaic microdeletions involving SCN1A in children diagnosed with DS. Through the evaluation of 237 affected individuals with DS who did not show SCN1A or PCHD19 mutations in prior sequencing analyzes, we identified two children with mosaic microdeletions covering the entire SCN1A region.

The smallest 20q11.2 microdeletion causing intellectual disability and dysmorphic features.

The 20q11.2 microdeletion is a rare chromosomal aberration characterized by intellectual disability (ID), motor developmental delay, neonatal feeding problems, and facial dysmorphism. Here, a 2-year- and 6-month-old Japanese girl with a 1.

Comprehensive functional genomics using Caenorhabditis elegans as a model organism.

We have been working on functional genomics using C. elegans as a model organism. We first used cell-type specific markers and preexisting mutants to investigate how genotype-phenotype causal relationships are regulated.

Characteristics of rare and private deletions identified in phenotypically normal individuals.

Genomic copy number variations (CNVs) identified through chromosomal microarray testing must be validated to confirm whether they are pathogenically and functionally relevant to their respective clinical features. Although larger deletions have a higher probability to be pathogenic, this is not always true. Phenotypically normal individuals showed five CNV deletions larger than 1.

A Video Report of Brain-Lung-Thyroid Syndrome in a Japanese Female With a Novel Frameshift Mutation of the Gene.

Benign hereditary chorea is a rare autosomal-dominant disorder that is characterized by childhood-onset nonprogressive chorea and normal cognitive function. Defects in on chromosome 14q13, which encodes thyroid transcription factor 1, produce a concurrent clinical manifestation of chorea, respiratory distress, and hypothyroidism known as "brain-lung-thyroid syndrome." Here, the authors describe a video report of benign hereditary chorea in a Japanese female with a novel frameshift mutation of (c.

An Xq22.1q22.2 nullisomy in a male patient with severe neurological impairment.

The proteolipid protein 1 gene (PLP1) is located on chromosome Xq22.2 and is related to X-linked recessive leukoencephalopathy (Pelizaeus-Merzbacher disease: PMD). Compared to PLP1 duplications, which are a major contributor to PMD, chromosomal deletions in this region are rare and only a few PMD patients with small deletions have been reported, suggesting that large deletions of this region would cause embryonic lethality.

Possible genes responsible for developmental delay observed in patients with rare 2q23q24 microdeletion syndrome: Literature review and description of an additional patient.

Cases of 2q23q24 microdeletion syndrome are rare. Patients with chromosomal deletions in this region often show language impairment and/or developmental delay of variable severity. Previous genotype-phenotype correlation study suggested GALNT13 and KCNJ3 as possible candidate genes for such phenotypes.

Amelioration of intractable epilepsy by adjunct vagus nerve stimulation therapy in a girl with a CDKL5 mutation.

We report the case of on an 8-year-old girl with a cyclin-dependent kinase-like 5 mutation and who underwent vagus nerve stimulation (VNS) therapy for 2years. She had developed epilepsy at the age of 6months and had severe developmental delays. Initially, she had tonic and tonic-clonic seizures; however, around the age of 5years, she also developed epileptic spasms.

The first Japanese case of leukodystrophy with ovarian failure arising from novel compound heterozygous AARS2 mutations.

Even now, only a portion of leukodystrophy patients are correctly diagnosed, though various causative genes have been identified. In the present report, we describe a case of adult-onset leukodystrophy in a woman with ovarian failure. By whole-exome sequencing, a compound heterozygous mutation consisting of NM_020745.

Abdominal paraganglioma in a young woman with 1p36 deletion syndrome.

1p36 deletion syndrome is the most common terminal deletion syndrome, and the genomic regions that contribute to specific 1p36 deletion syndrome-related phenotypes were recently identified. Deletions in the 1p36 region have been documented in various tumor tissues, which indicates correlation between loss of heterozygosity of 1p36 and tumor development, and the existence of tumor suppressors in this region. Therefore, it was suspected that patients with 1p36 deletion syndrome have a higher risk of tumor development; however, only a few child cases of neuroblastoma with 1p36 deletion syndrome have been reported.

Concurrent occurrence of an inherited 16p13.11 microduplication and a de novo 19p13.3 microdeletion involving MAP2K2 in a patient with developmental delay, distinctive facial features, and lambdoid synostosis.

A female patient presented with developmental delay, distinctive facial features, and congenital anomalies, including a heart defect and premature lambdoid synostosis. The patient showed a paternally inherited 16p13.11 microduplication and a de novo 19p13.

mutations in three Japanese pedigrees with hereditary cavernous malformation.

Cerebral cavernous malformation is a neurovascular abnormality that can cause seizures, focal neurological deficits and intracerebral hemorrhage. Familial forms of this condition are characterized by formation of multiple lesions and are autosomal-dominantly inherited via /, and / mutations. We identified three truncating mutations in from three Japanese families with CCMs: a novel frameshift mutation, a known frameshift mutation and a known splice-site mutation that had not been previously analyzed for aberrant splicing.

Exome Sequencing Identified CCER2 as a Novel Candidate Gene for Moyamoya Disease.

The etiology of Moyamoya disease (MMD) is still largely unclear, despite identification of RNF213 as the most significant susceptibility gene in East Asian patients. Following up our previous study confirming genetic heterogeneity in Japanese patients with MMD, we extensively surveyed novel candidate genes for a new perspective on the etiology of this disease. Two characteristic pedigrees without susceptibility variants in RNF213 were selected for whole-exome sequencing; 1 harbored 3 affected members, and the other included discordant monozygotic twins.

Novel SLC16A2 mutations in patients with Allan-Herndon-Dudley syndrome.

Allan-Herndon-Dudley syndrome (AHDS) is an X-linked disorder caused by impaired thyroid hormone transporter. Patients with AHDS usually exhibit severe motor developmental delay, delayed myelination of the brain white matter, and elevated T3 levels in thyroid tests. Neurological examination of two patients with neurodevelopmental delay revealed generalized hypotonia, and not paresis, as the main neurological finding.

A 12p13 GRIN2B deletion is associated with developmental delay and macrocephaly.

N-methyl D-aspartate receptor subtype 2B (GluN2B), encoded by GRIN2B, is one of the components of the N-methyl D-aspartate receptor protein. Aberrations in GRIN2B have been reported to be responsible for various types of neurodevelopmental disorders. We report a Japanese boy with an ~2 Mb interstitial deletion in 12p13 involving the entire GRIN2B gene, who presented with intellectual disability, motor developmental delay and marked macrocephaly.