Biallelic loss-of-function variants in the centriolar protein CCP110 leads to a ciliopathy-like phenotype(s).

CCP110 (centriolar coiled coil protein 110, also known as CP110) is one of the essential proteins localized in the centrosome that plays critical roles in the regulation of the cell cycle and also in the initiation of ciliogenesis. So far, no human congenital disorders have been identified to be associated with pathogenic variants of CCP110. Mice with biallelic loss-of-function variants of Ccp110 (Ccp110-/-) are known to manifest multiple organ defects, including a small body size, polydactyly, omphalocele, congenital heart defects, cleft palate, short ribs, and a small thoracic cage, a pattern of abnormalities closely resembling that in "ciliopathies" in humans. Herein, we report a 7-month-old male infant who presented with growth failure and skeletal abnormalities, including a narrow thorax and severe brachydactyly. Trio exome analysis of the genomic DNA of the patient and his parents showed that the patient was a compound heterozygote for truncating variants of CCP110, including a frameshift variant NM_001323572.2:c.856_857del, p.(Val286Leufs*5) inherited from the father, and a nonsense variant NM_001323572.2:c.1129C>T, p.(Arg377*) inherited from the mother. The strikingly similar pattern of malformations between Ccp110-/- mice and the 7-month old male infant reported herein carrying unequivocal truncating CCP110 variants strongly supports the contention that CCP110 is a novel disease-causative gene.

Breakpoints in complex chromosomal rearrangements correspond to transposase-accessible regions of DNA from mature sperm.

Constitutional complex chromosomal rearrangements (CCRs) are rare cytogenetic aberrations arising in the germline via an unknown mechanism. Here we analyzed the breakpoint junctions of microscopically three-way or more complex translocations using comprehensive genomic and epigenomic analyses. All of these translocation junctions showed submicroscopic genomic complexity reminiscent of chromothripsis. The breakpoints were clustered within small genomic domains with junctions showing microhomology or microinsertions. Notably, all of the de novo cases were of paternal origin. The breakpoint distributions corresponded specifically to the ATAC-seq (assay for transposase-accessible chromatin with sequencing) read data peak of mature sperm and not to other chromatin markers or tissues. We propose that DNA breaks in CCRs may develop in an accessible region of densely packaged chromatin during post-meiotic spermiogenesis.

Prenatal diagnosis of distal 13q deletion syndrome in a fetus with esophageal atresia: a case report and review of the literature.

BACKGROUND: Chromosome 13q deletion syndrome shows variable clinical features related to the different potential breakpoints in chromosome 13q. The severely malformed phenotype is known to be associated with the deletion of a critical region in 13q32. However, esophageal atresia is a rare symptom and the relevant region is unknown. Thus, determining the association between accurate breakpoints and new clinical features is essential. CASE PRESENTATION: A 28-year-old Japanese primigravid woman was referred for fetal growth restriction, absence of a gastric bubble, cerebellar hypoplasia, overlapping fingers, and polyhydramnios at 31 weeks gestation. At 38 + 0 weeks, she delivered a 1774 g female infant. The infant presented with isolated esophageal atresia (Gross type A), Dandy-Walker malformation, right microphthalmia, left coloboma, overlapping fingers, pleurocentrum in the thoracic vertebrae, reduced anogenital distance, and hearing loss. Her karyotype was diagnosed as 46,XX,del(13)(q32.1-qter) by amniocentesis, but array comparative genomic hybridization after birth revealed the deletion of 13q31.3-qter. At 48 days after birth, the infant underwent surgery for esophageal atresia and was later discharged from the hospital at 7 months of age. CONCLUSION: This case report and the literature reviews supports the previous findings on the pathological roles of haploinsufficiency of the ZIC2/ZIC5 in Dandy-Walker malformation and the EFBN2 haploinsufficiency in eye malformation and hearing loss. Furthermore, the possible involvement of IRS2, COLA1, and COLA2 in eye malformation were identified. This is the first case of 13q deletion syndrome with esophageal atresia (Gross A), but it may be a symptom of VATER/VACTER association (vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal malformations, and limb defects), as in the previous cases. These symptoms might also be associated with EFBN2 haploinsufficiency, although further research is required.

Whole-exome analysis of 177 pediatric patients with undiagnosed diseases.

Recently, whole-exome sequencing (WES) has been used for genetic diagnoses of patients who remain otherwise undiagnosed. WES was performed in 177 Japanese patients with undiagnosed conditions who were referred to the Tokai regional branch of the Initiative on Rare and Undiagnosed Diseases (IRUD) (TOKAI-IRUD). This study included only patients who had not previously received genome-wide testing. Review meetings with specialists in various medical fields were held to evaluate the genetic diagnosis in each case, which was based on the guidelines of the American College of Medical Genetics and Genomics. WES identified diagnostic single-nucleotide variants in 66 patients and copy number variants (CNVs) in 11 patients. Additionally, a patient was diagnosed with Angelman syndrome with a complex clinical phenotype upon detection of a paternally derived uniparental disomy (UPD) [upd(15)pat] wherein the patient carried a homozygous DUOX2 p.E520D variant in the UPD region. Functional analysis confirmed that this DUOX2 variant was a loss-of-function missense substitution and the primary cause of congenital hypothyroidism. A significantly higher proportion of genetic diagnoses was achieved compared to previous reports (44%, 78/177 vs. 24-35%, respectively), probably due to detailed discussions and the higher rate of CNV detection.

Target enrichment long-read sequencing with adaptive sampling can determine the structure of the small supernumerary marker chromosomes.

Structural analysis of small supernumerary marker chromosomes (sSMCs) has revealed that many have complex structures. Structural analysis of sSMCs by whole genome sequencing using short-read sequencers is challenging however because most present with a low level of mosaicism and consist of a small region of the involved chromosome. In this present study, we applied adaptive sampling using nanopore long-read sequencing technology to enrich the target region and thereby attempted to determine the structure of two sSMCs with complex structural rearrangements previously revealed by cytogenetic microarray. In adaptive sampling, simple specification of the target region in the FASTA file enables to identify whether or not the sequencing DNA is included in the target, thus promoting efficient long-read sequencing. To evaluate the target enrichment efficiency, we performed conventional pair-end short-read sequencing in parallel. Sequencing with adaptive sampling achieved a target enrichment at about a 11.0- to 11.5-fold higher coverage rate than conventional pair-end sequencing. This enabled us to quickly identify all breakpoint junctions and determine the exact sSMC structure as a ring chromosome. In addition to the microhomology and microinsertion at the junctions, we identified inverted repeat structure in both sSMCs, suggesting the common generation mechanism involving replication impairment. Adaptive sampling is thus an easy and beneficial method of determining the structures of complex chromosomal rearrangements.

Establishment of in-hospital clinical network for patients with neurofibromatosis type 1 in Nagoya University Hospital.

Neurofibromatosis type 1 (NF1) is a genetic multisystem disorder. Clinicians must be aware of the diverse clinical features of this disorder in order to provide optimal care for it. We have set up an NF1 in-hospital medical care network of specialists regardless of patient age, launching a multidisciplinary approach to the disease for the first time in Japan. From January 2014 to December 2020, 246 patients were enrolled in the NF1 patient list and medical records. Mean age was 26.0 years ranging from 3 months to 80 years. The number of patients was higher as age at first visit was lower. There were 107 males (41%) and 139 females. After 2011, the number of patients has increased since the year when the medical care network was started. Regarding orthopedic signs, scoliosis was present in 60 cases (26%), and bone abnormalities in the upper arm, forearm, and tibia in 8 cases (3.5%). Neurofibromas other than cutaneous neurofibromas were present in 90 cases (39%), and MPNST in 17 cases (7.4%). We launched a multidisciplinary NF1 clinic system for the first time in Japan. For patients with NF1, which is a hereditary and systemic disease associated with a high incidence of malignant tumors, it will be of great benefit when the number of such clinics in Japan and the rest of Asia is increased.

The involvement of U-type dicentric chromosomes in the formation of terminal deletions with or without adjacent inverted duplications.

An inverted duplication with a terminal deletion (inv-dup-del) is one of the complex constitutional structural rearrangements that can occur in a chromosome. Although breakages of dicentric chromosome have been suggested, the precise mechanism of this is yet to be fully understood. In our present study, we investigated the genomic structure of 10 inv-dup-del cases to elucidate this mechanism. Two recurrent 8p inv-dup-del cases harbored a large copy-number-neutral region between the duplication and deletion in common. Although the other non-recurrent cases did not appear to have this copy-number-neutral region, refined sequencing analysis identified that they contained a small intervening region at the junction between the inverted and non-inverted segment. The size of this small intervening region ranged from 1741 to 3728 bp. Combined with a presence of microhomology at the junction, a resolution of the replication fork stalling through template switching within the same replication fork is suggested. We further observed two cases with mosaicism of the dicentric chromosome and various structural rearrangements related to the dicentric chromosome. Refined analysis allowed us to identify different breakpoints on the same chromosome in the same case, implicating multiple rounds of U-type formation and its breakage. From these results, we propose that a replication-based mechanism generates unstable dicentric chromosomes and that their breakage leads to the formation of inv-dup-dels and other related derivative chromosomes.

Role of the Embodied Cognition Process in Perspective-Taking Ability During Childhood.

This study examined developmental changes in Level-2 visual perspective taking (VPT2) in 90 children aged 4-12 years and tested the role of their ability to mentally simulate changes to their bodily locations (self-motion imagery; SMI). Performance of a mental toy rotation task and a self-motion (SM) task (changing location of children) was superior to that of VPT2 and SMI tasks. Task performance of SMI was better than that of VPT2 before 10;0 (years;months). Furthermore, egocentric responses in VPT2 and SMI tasks were significantly more frequent than those in the mental rotation and SM tasks before 10;3. These findings suggest the involvement of embodied cognitive processes in perspective taking and the advantage of utilizing bodily information by age 10.

Factors related to survival discharge in trisomy 18: A retrospective multicenter study.

Infants with trisomy 18 (T18) previously had a poor prognosis; however, the intensive care of these patients has markedly diversified the prognosis. We investigated the current situation of patients with T18, clarified factors for survival discharge, and surveyed actual home healthcare. A total of 117 patients with T18 admitted to nine institutions between 2000 and 2015 were retrospectively investigated. After excluding four patients whose outcomes were unclear, we divided 113 patients into two groups-the survival discharge group (n = 52) and the death discharge group (n = 61)-and compared maternal factors, perinatal factors, neonatal factors, and therapeutic factors between the groups. In addition, home healthcare, readmission, utilization of respite care and home nursing, and cause of death among the survival group were surveyed. Fifty-two (44%) patients with T18 survived at discharge and their 1-year survival rate was 29%. The survival group had a longer gestation period, larger physique, and longer survival time, compared to the death group. Independent factors associated with survival discharge were the absence of an extremely low birthweight infant (ELBWI), the absence of esophageal atresia and patent ductus arteriosus, and cardiovascular surgery. All surviving patients required some home healthcare. The most frequent cause of death was a respiratory disorder. We recommend discussing the treatment strategy with families in the presence of neonatologists or pediatric surgeons, who can explain differences in prognosis, based on the gestation period, birthweight, severity of cardiovascular disease, and cardiovascular surgery.

Findings of amplitude-integrated electroencephalogram recordings and serum vitamin B6 metabolites in perinatal lethal hypophosphatasia during enzyme replacement therapy.

Hypophosphatasia (HPP) is a rare disorder caused by low serum tissue non-specific alkaline phosphatase (ALP) activity due to hypomorphic mutations in the ALPL gene. HPP is characterized by defective bone mineralization. It frequently accompanies pyridoxine-responsive seizures. Because alkaline phosphatase change pyridoxal 5' phosphate (PLP) into pyridoxal (PL), which can cross the blood brain barrier and regulates inhibitory neurotransmitter gamma-aminobutyric acid. The female patient was born at a gestational age of 37 weeks 2 days. She presented severe respiratory disorder due to extreme thoracic hypoplasia. With the extremely low serum ALP value (14 IU/L), she was clinically diagnosed as HPP. The diagnosis was confirmed with genetic testing. On day1, the subclinical seizures were detected by aEEG. Together with enzyme replacement therapy by asfotase alfa, pyridoxine hydrochloride was administered, then the seizures were rapidly controlled. While confirming that there was no seizure by aEEG monitoring, pyridoxine hydrochloride was gradually discontinued after 1 month. Before administration of pyridoxine hydrochloride, PL was extremely low (4.7 nM) and PLP was increased (1083 nM). After the withdrawal, PL was increased to 84.9 nM only by enzyme replacement. Monitoring with aEEG enabled early intervention for pyridoxine responsive seizures. Confirming increased serum PL concentration is a prudent step in determining when to reduce or discontinue pyridoxine hydrochloride during enzyme replacement therapy.

Factors related to home health-care transition in trisomy 13.

Trisomy 13 (T13) is accompanied by severe complications, and it can be challenging to achieve long-term survival without aggressive treatment. However, recently, some patients with T13 have been receiving home care. We conducted this study to investigate factors related to home health-care transition for patients with T13.We studied 28 patients with T13 born between January 2000 and December 2014. We retrospectively compared nine home care transition patients (the home care group) and 19 patients that died during hospitalization (the discharge at death group). The median gestational age of the patients was 36.6 weeks, with a median birth weight of 2,047 g. Currently, three patients (11%) have survived, and 25 (89%) have died. The home care group exhibited a significantly longer gestational age (38.9 vs. 36.3 weeks, p = 0.039) and significantly larger occipitofrontal circumference Z score (-0.04 vs. -0.09, p = 0.019). Congenital heart defects (CHD) was more frequent in the discharge at death group, with six patients in the home care group and 18 patients in the discharge at death group (67% vs. 95%, p = 0.047), respectively. Survival time was significantly longer in the home care group than in the discharge at death group (171 vs. 19 days, p = 0.012). This study has shown that gestational age, occipitofrontal circumference Z score at birth, and the presence of CHD are helpful prognostic factors for determining treatment strategy in patients with T13.

Preserved search asymmetry in the detection of fearful faces among neutral faces in individuals with Williams syndrome revealed by measurement of both manual responses and eye tracking.

BACKGROUND: Individuals with Williams syndrome (WS) exhibit an atypical social phenotype termed hypersociability. One theory accounting for hypersociability presumes an atypical function of the amygdala, which processes fear-related information. However, evidence is lacking regarding the detection mechanisms of fearful faces for individuals with WS. Here, we introduce a visual search paradigm to elucidate the mechanisms for detecting fearful faces by evaluating the search asymmetry; the reaction time when both the target and distractors were swapped was asymmetrical. METHODS: Eye movements reflect subtle atypical attentional properties, whereas, manual responses are unable to capture atypical attentional profiles toward faces in individuals with WS. Therefore, we measured both eye movements and manual responses of individuals with WS and typically developed children and adults in visual searching for a fearful face among neutral faces or a neutral face among fearful faces. Two task measures, namely reaction time and performance accuracy, were analyzed for each stimulus as well as gaze behavior and the initial fixation onset latency. RESULTS: Overall, reaction times in the WS group and the mentally age-matched control group were significantly longer than those in the chronologically age-matched group. We observed a search asymmetry effect in all groups: when a neutral target facial expression was presented among fearful faces, the reaction times were significantly prolonged in comparison with when a fearful target facial expression was displayed among neutral distractor faces. Furthermore, the first fixation onset latency of eye movement toward a target facial expression showed a similar tendency for manual responses. CONCLUSIONS: Although overall responses in detecting fearful faces for individuals with WS are slower than those for control groups, search asymmetry was observed. Therefore, cognitive mechanisms underlying the detection of fearful faces seem to be typical in individuals with WS. This finding is discussed with reference to the amygdala account explaining hypersociability in individuals with WS.

Phenotype-genotype correlations of PIGO deficiency with variable phenotypes from infantile lethality to mild learning difficulties.

Inherited GPI (glycosylphosphatidylinositol) deficiencies (IGDs), a recently defined group of diseases, show a broad spectrum of symptoms. Hyperphosphatasia mental retardation syndrome, also known as Mabry syndrome, is a type of IGDs. There are at least 26 genes involved in the biosynthesis and transport of GPI-anchored proteins; however, IGDs constitute a rare group of diseases, and correlations between the spectrum of symptoms and affected genes or the type of mutations have not been shown. Here, we report four newly identified and five previously described Japanese families with PIGO (phosphatidylinositol glycan anchor biosynthesis class O) deficiency. We show how the clinical severity of IGDs correlates with flow cytometric analysis of blood, functional analysis using a PIGO-deficient cell line, and the degree of hyperphosphatasia. The flow cytometric analysis and hyperphosphatasia are useful for IGD diagnosis, but the expression level of GPI-anchored proteins and the degree of hyperphosphatasia do not correlate, although functional studies do, with clinical severity. Compared with PIGA (phosphatidylinositol glycan anchor biosynthesis class A) deficiency, PIGO deficiency shows characteristic features, such as Hirschsprung disease, brachytelephalangy, and hyperphosphatasia. This report shows the precise spectrum of symptoms according to the severity of mutations and compares symptoms between different types of IGD.

Disparities in visuo-spatial constructive abilities in Williams syndrome patients with typical deletion on chromosome 7q11.23.

BACKGROUND: Williams syndrome (WS) is known for its uneven cognitive abilities, especially the difficulty in visuo-spatial cognition, though there are some inter-individual phenotypic differences. It has been proposed that the difficulty in visuo-spatial cognition of WS patients can be attributed to a haploinsufficiency of some genes located on the deleted region in 7q11.23, based on an examination of atypical deletions identified in WS patients with atypical cognitive deficits. According to this hypothesis, the inter-individual differences in visuo-spatial cognitive ability arise from variations in deletion. METHODS: We investigated whether there were inter-individual differences in the visuo-spatial constructive abilities of five unrelated WS patients with the typical deletion on chromosome 7q11.23 that includes the candidate genes contributing visuo-spatial difficulty in WS patients. We used tests with three-dimensional factors such as Benton's three-dimensional block construction test, which are considered to be more sensitive than those with only two-dimensional factors. RESULTS: There were diverse inter-individual differences in the visuo-spatial constructive abilities among the present participants who shared the same typical genomic deletion of WS. One of the participants showed almost equivalent performances to typically developing adults in those tests. CONCLUSION: In the present study, we found a wide range of cognitive abilities in visuo-spatial construction even among the patients with a common deletion pattern of WS. The findings suggest that attributing differences in the phenotypes entirely to genetic factors such as an atypical deletion may not be always correct.

Typical visual search performance and atypical gaze behaviors in response to faces in Williams syndrome.

BACKGROUND: Evidence indicates that individuals with Williams syndrome (WS) exhibit atypical attentional characteristics when viewing faces. However, the dynamics of visual attention captured by faces remain unclear, especially when explicit attentional forces are present. To clarify this, we introduced a visual search paradigm and assessed how the relative strength of visual attention captured by a face and explicit attentional control changes as search progresses. METHODS: Participants (WS and controls) searched for a target (butterfly) within an array of distractors, which sometimes contained an upright face. We analyzed reaction time and location of the first fixation-which reflect the attentional profile at the initial stage-and fixation durations. These features represent aspects of attention at later stages of visual search. The strength of visual attention captured by faces and explicit attentional control (toward the butterfly) was characterized by the frequency of first fixations on a face or butterfly and on the duration of face or butterfly fixations. RESULTS: Although reaction time was longer in all groups when faces were present, and visual attention was not dominated by faces in any group during the initial stages of the search, when faces were present, attention to faces dominated in the WS group during the later search stages. Furthermore, for the WS group, reaction time correlated with eye-movement measures at different stages of searching such that longer reaction times were associated with longer face-fixations, specifically at the initial stage of searching. Moreover, longer reaction times were associated with longer face-fixations at the later stages of searching, while shorter reaction times were associated with longer butterfly fixations. CONCLUSIONS: The relative strength of attention captured by faces in people with WS is not observed at the initial stage of searching but becomes dominant as the search progresses. Furthermore, although behavioral responses are associated with some aspects of eye movements, they are not as sensitive as eye-movement measurements themselves at detecting atypical attentional characteristics in people with WS.

Hydrogen-rich water ameliorates bronchopulmonary dysplasia (BPD) in newborn rats.

Bronchopulmonary dysplasia (BPD) is characterized by developmental arrest of the alveolar tissue. Oxidative stress is causally associated with development of BPD. The effects of hydrogen have been reported in a wide range of disease models and human diseases especially caused by oxidative stress. We made a rat model of BPD by injecting lipopolysaccharide (LPS) into the amniotic fluid at E16.5. The mother started drinking hydrogen-rich water from E9.5 and also while feeding milk. Hydrogen normalized LPS-induced abnormal enlargement of alveoli at P7 and P14. LPS increased staining for nitrotyrosine and 8-OHdG of the lungs, and hydrogen attenuated the staining. At P1, LPS treatment decreased expressions of genes for FGFR4, VEGFR2, and HO-1 in the lungs, and hydrogen increased expressions of these genes. In contrast, LPS treatment and hydrogen treatment had no essential effect on the expression of SOD1. Inflammatory marker proteins of TNFα and IL-6 were increased by LPS treatment, and hydrogen suppressed them. Treatment of A549 human lung adenocarcinoma epithelial cells with 10% hydrogen gas for 24 hr decreased production of reactive oxygen species in both LPS-treated and untreated cells. Lack of any known adverse effects of hydrogen makes hydrogen a promising therapeutic modality for BPD. Pediatr Pulmonol. 2016; 51:928-935. © 2016 Wiley Periodicals, Inc.

[Cognitive and linguistic abilities of a boy with PVL showing relatively higher VIQ compared to PIQ].

In this study, we investigated the cognitive processing and language abilities of a 13-year-old boy with moderate periventricular leukomalacia (PVL), spastic diplegia and exotropia who had discrepant scores in the verbal intelligence quotient (VIQ) and performance intelligence quotient (PIQ) in the Wechsler Intelligence Scale for Children, third edition (VIQ; 82 > PIQ; under 40). In the Kaufman Assessment Battery for Children and Das-Naglieri Cognitive Assessment System, his performance was poor at simultaneous processing compared to sequential processing. He could not copy three-dimensional figures, and he could place only two out of eight blocks correctly in the second level models of Benton three-dimensional block construction test, showing visuospatial impairment typical of patients with PVL. Despite the relatively high score in VIQ, there was a gap among the scores of the subtests in the Illinois Test of Psycholinguistic Abilities. He tended to get low scores in tests that required visual abilities. In addition, there was also an impairment in reading fluency tested by the Diagnostic Criteria and Medical Guideline for Specific Developmental Disorders. He was much less fluent in reading syllables, words or sentences (6.0 SD or more compared to 12-year-old boys). The relatively higher score in VIQ superficially suggests adequate language ability. However, in the present study, precise investigation revealed some discrepancies even within the field of language. Thus, defining stronger and weaker points of a patient is important in order to determine optimal medical or educational approaches.

Developmental changes in mental rotation ability and visual perspective-taking in children and adults with Williams syndrome.

Williams syndrome (WS) is a genetic disorder caused by the partial deletion of chromosome 7. Individuals with WS have atypical cognitive abilities, such as hypersociability and compromised visuospatial cognition, although the mechanisms underlying these deficits, as well as the relationship between them, remain unclear. Here, we assessed performance in mental rotation (MR) and level 2 visual perspective taking (VPT2) tasks in individuals with and without WS. Individuals with WS obtained lower scores in the VPT2 task than in the MR task. These individuals also performed poorly on both the MR and VPT2 tasks compared with members of a control group. For the individuals in the control group, performance scores improved during development for both tasks, while the scores of those in the WS group improved only in the MR task, and not the VPT2 task. Therefore, we conducted a second experiment to explore the specific cognitive challenges faced by people with WS in the VPT2 task. In addition to asking participants to change their physical location (self-motion), we also asked them to adopt a third-person perspective by imagining that they had moved to a specified location (self-motion imagery). This enabled us to assess their ability to simulate the movement of their own bodies. The performance in the control group improved in both the self-motion and self-motion imagery tasks and both performances were correlated with verbal mental age. However, we did not find any developmental changes in performance for either task in the WS group. Performance scores for the self-motion imagery task in the WS group were low, similar to the scores observed for the VPT2 in this population. These results suggest that MR and VPT2 tasks involve different processes, and that these processes develop differently in people with WS. Moreover, difficulty completing VPT2 tasks may be partly because of an inability of people with WS to accurately simulate mental body motion.

Prenatal diagnosis of X-linked recessive Lenz microphthalmia syndrome.

Lenz microphthalmia syndrome comprises microphthalmia-anophthalmia with mental retardation, malformed ears and skeletal anomalies, and is inherited in an X-linked recessive pattern. In 2004, it was reported that the missense mutation (BCL-6 co-repressor gene [BCOR] c.254C>T, p.P85L) in a single family with Lenz microphthalmia syndrome co-segregated with the disease phenotype. We report a case of prenatal diagnosis for X-linked recessive Lenz microphthalmia syndrome with the mutation. A 32-year-old gravida 5, para 2 Japanese woman was referred to Nagoya City University Hospital at 15 weeks of gestation. After genetic counseling and informed consent, amniocentesis was performed for fetal karyotyping, which was 46,XY. Using the extracted DNA from cultured amniotic cells, fetal search for BCOR c.254C>T mutation was undertaken. The couple requested medical termination of pregnancy, and the postabortion examination confirmed the diagnosis. This is the third report of a BCOR mutation, associated with X-linked syndromic microphthalmia, and most importantly, it is always the same mutation. The prenatal genetic diagnosis of the Lenz microphthalmia syndrome allowed time for parental counseling and delivery planning.