To date, only 13 studies have described patients with large overlapping deletions of 10p11.2-p12. These individuals shared a common phenotype characterized by intellectual disability, developmental delay, distinct facial dysmorphic features, abnormal behaviour, visual impairment, cardiac malformation, and cryptorchidism in males. Molecular cytogenetic analysis revealed that the deletion in this chromosomal region shares a common smallest region of overlap (SRO) of 80 kb, which contains only the WAC gene (WW-domain-containing adaptor with coiled coil). In this clinical case report, we report a 5-year-old girl, born from non-consanguineous parents, with a 10p11.22p11.21 microdeletion. She presents clinical features that overlap with other patients described in the literature, such as dysmorphic traits, speech delay, and behavioural abnormalities (hyperactivity), even though the WAC gene is not involved in the microdeletion. Our results are the first to highlight that the deletion described here represents a contiguous gene syndrome that is enough to explain the distinct phenotype but partially overlaps with the previous cases reported in the literature, even though the same genes are not involved. In particular, in this study, we speculate about the role of the WAC gene that seems to be associated with normal motor development. In fact, we found that our patient is the only one described in the literature with a large deletion in the 10p11.22p11.21 region without the involvement of the WAC gene deletion, and, interestingly, the patient did not have motor delay.

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UNASSIGNED: Primary biliary cholangitis (PBC) is a rare and chronic autoimmune liver disease characterized by the progressive destruction of small intrahepatic bile ducts that may eventually lead to cirrhosis. PBC with features of autoimmune hepatitis (AIH) has rarely been reported in pediatric patients with genetic defects. We present the case of an adolescent with chromosome 14q24.1q24.2 deletion who was given the diagnosis of stage IV PBC with features of AIH.
UNASSIGNED: A 19-year-old male adolescent with multiple congenital abnormalities and an intellectual disability presented with abnormal liver enzymes levels and pruritus for more than 5 years. Laboratory examinations revealed elevated levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transpeptidase. After the exclusion of viral hepatitis, alpha-1 antitrypsin deficiency, Wilson\'s disease, and other genetic cholestatic liver diseases by laboratory tests and whole exome sequencing, a liver biopsy was performed and stage IV PBC was diagnosed. Notably, features of AIH were also noted in the histopathological report, indicating the presence of PBC with AIH features. The patient responded well to a combination therapy of ursodeoxycholic acid and steroids. Array comparative genomic hybridization analysis performed to study the congenital abnormalities revealed a 3.89 Mb 14q24.1q24.2 deletion.
UNASSIGNED: PBC with AIH features has rarely been reported in an adolescent with a chromosomal abnormality. The present case can increase awareness for early-onset PBC and its possible correlation with chromosomal defects.

UNASSIGNED: Hereditary forms of intellectual disability (ID), an estimated prevalence ranging between 1% and 3% in the general population, are among the most important problems in health care. Especially, autosomal-recessive ID has a very heterogeneous molecular basis and a lack of specific phenotypic features.
UNASSIGNED: Here, we report on two unrelated patients with autosomal-recessive ID, microcephaly, and autistic features and review the patients with TRAPPC9-related ID. Whole-exome sequencing and array CGH were performed for molecular diagnosis of the patients.
UNASSIGNED: The first case has a microdeletion on chromosome 8q24.23-q24.3 region which is 1.7 Mb in length and includes the last 5 exons of TRAPPC9, and c.3435delG [p.Thr1146Profs*8] deletion. The second case has a homozygous missense c.623A>C (p.His208Pro) variant in TRAPPC9 which is detected by means of whole-exome sequencing study of the proband. We also reviewed the clinical findings and mutation spectrum of all patients with TRAPPC9-related ID reported so far.
UNASSIGNED: Our study showed that the most consistent clinical findings for TRAPPC9-related ID are ID, microcephaly, and some structural brain MRI abnormalities. The mutations in the TRAPPC9 are scattered throughout all exons of TRAPPC9 indicating there is no hot spot mutation region in this gene.

BACKGROUND: Despite the efforts that have been made to standardize the interpretation of variants, in some cases, their pathogenicity remains vague and confusing, and sometimes their interpretation does not help clinicians to establish clinical correlation using genetic test results. This study aims to shed more lights on these challenging variants.
METHODS: In a clinical setting, the variants found from 81 array CGH and 79 whole exome sequencing (WES) in patients with congenital anomalies were interpreted based on American College of Medical Genetics and Genomics guidelines.
RESULTS: In this study, the interpretation of the disease-causing variants and the variants with uncertain clinical significance detected by WES was far more challenging than the variants detected by array CGH. The presence of unreported clinical symptoms, incomplete penetrance, variable expressivity, parents\' reluctance to analyze segregation in the family, and the limitations of prenatal tests, were among the challenging factors in the interpretation of variants in this study.
CONCLUSIONS: A careful study of the pedigree and disease mode of inheritance, as well as a careful clinical examination of the carrier parents in diseases with autosomal dominant inheritance, are among the primary strategies for determining the clinical significance of the variants. Continued efforts to mitigate these challenges are needed to improve the interpretation of variants.

BACKGROUND: The diagnosis of corpus callosum anomalies by prenatal ultrasound has improved over the last decade because of improved imaging techniques, scanning skills, and the routine implementation of transvaginal neurosonography.
OBJECTIVE: Our aim was to investigate all cases of incomplete agenesis of the corpus callosum and to report the sonographic characteristics, the associated anomalies, and the perinatal outcomes.
METHODS: We performed a retrospective analysis of cases from January 2007 to December 2017 with corpus callosum anomalies, either referred for a second opinion or derived from the prenatal ultrasound screening program in a single tertiary referral center. Cases with complete agenesis were excluded from the analysis. Standardized investigation included a detailed fetal ultrasound including neurosonogram, fetal karyotyping (standard karyotype or array comparative genomic hybridization) and fetal magnetic resonance imaging. The pregnancy outcome was collected, and pathologic investigation in case of termination of the pregnancy or fetal or neonatal loss was compared with the prenatal findings. The pregnancy and fetal or neonatal outcomes were reported. The neurologic assessment was conducted by a pediatric neurologist using the Bayley Scales of Infant Development-II and the standardized Child Development Inventory when the Bayley investigation was unavailable.
RESULTS: Corpus callosum anomalies were diagnosed in 148 cases during the study period, 62 (41.9%) of which were excluded because of complete agenesis, and 86 fetuses had partial agenesis (58.1%). In 20 cases, partial agenesis (23.2%) was isolated, whereas 66 (76.7%) presented with different malformations among which 29 cases (43.9%) were only central nervous system lesions, 21 cases (31.8%) were non-central nervous system lesions, and 16 cases (24.3%) had a combination of central nervous system and non-central nervous system lesions. The mean gestational age at diagnosis for isolated and non-isolated cases was comparable (24.29 [standard deviation, 5.05] weeks and 24.71 [standard deviation, 5.35] weeks, respectively). Of the 86 pregnancies with partial agenesis, 46 patients opted for termination of the pregnancy. Neurologic follow-up data were available for 35 children. The overall neurologic outcome was normal in 21 of 35 children (60%); 3 of 35 (8.6%) showed mild impairment and 6 of 35 (17.1%) showed moderate impairment. The remaining 5 of 35 (14.3%) had severe impairment. The median duration of follow-up for the isolated form was 45.6 months (range, 36-52 months) and 73.3 months (range, 2-138 months) for the nonisolated form.
CONCLUSIONS: Partial corpus callosum agenesis should be accurately investigated by neurosonography and fetal magnetic resonance imaging to describe its morphology and the associated anomalies. Genetic anomalies are frequently present in nonisolated cases. Efforts must be taken to improve ultrasound diagnosis of partial agenesis and to confirm its isolated nature to enhance parental counseling. Although 60% of children with prenatal diagnosis of isolated agenesis have a favorable prognosis later in life, they often have mild to severe disabilities including speech disorders at school age and behavior and motor deficit disorders that can emerge at a later age.

UNASSIGNED: Chromosomal abnormalities are mostly found in 0.5-0.8% of live-born infants with developmental and morphological defects. Paracentric inversions are structural intrachromosomal rearrangements resulting in a risk of chromosomally unbalanced gametes in carriers.
UNASSIGNED: Herein, we report a patient with dicentric rearrangement of chromosome 18 due to maternal paracentric inversion of chromosome 18. The patient was a girl, aged 3 years and 11 months. She was referred due to multiple congenital abnormalities, severe intellectual disability, and motor retardation. She had microcephaly, prominent metopic suture, synophrys, epicanthic folds, telecanthus, wide-set alae nasi, wide columella, bilateral cleft lip and palate, pectus carinatum, umbilical hernia, pes planus, and anteriorly displaced anus. She had bilateral external auditory canal stenosis and mild right-sided and moderate left-sided sensorineural hearing loss. Echocardiography showed secundum-type atrial septal defect and mild tricuspid failure. Brain magnetic resonance imaging showed only thinning of posterior areas of the corpus callosum. Chromosome analysis showed 46,XX,dic rec(18) by GTG and C banding. Dicentric chromosome was confirmed by fluorescence in situ hybridization analysis. Paternal karyotype was normal 46,XY but maternal chromosome analysis showed a paracentric inversion in chromosome 18 with 46,XX,inv(18)(q11.2?q21.3?) karyotype. Array CGH was performed on a peripheral blood sample from the patient and showed duplication at 18p11.32p11.21 and 18q11.1q11.2, and deletion at 18q21.33q23. The patient\'s final karyotype is arr 18p11.32p11.21(64,847_15,102,598)×3,18q11.1q11.2(18,542,074_22,666,470)×3,18q21.33q23(59,784,364_78,010,032)×1.
UNASSIGNED: To the best of our knowledge, this is the first report of a patient with dicentric chromosome 18 due to a parental paracentric inversion of chromosome 18. We present the genotype-phenotype correlation with literature review.

Hypotonia is a symptom of diminished tone of skeletal muscle and can be nongenetic or a part of genetic syndrome. Hypotonia, developmental delay, and facial dysmorphism are nonspecific findings observed in many genetic syndromes mostly in chromosomal microdeletion and duplication. Here we report a case with severe hypotonia and facial dysmorphism, diagnosed with deletion at 6q13q14.3 by array comparative genomic hybridization (CGH) at very early age. Recent genetic diagnostic technologies such as array CGH may enable clinicians to diagnose chromosomal abnormalities earlier and provide appropriate medical management.

The PARK2 gene is located on 6q26, encodes ubiquitin-E3- ligase, and is a transcriptional repressor of p53. It contains 12 exons. PARK2 copy number variants has been reported in various types of neurodevelopmental disorders, namely schizophrenia, Parkinson\'s disease (PD), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). In this retrospective study, nine cases (five with microdeletion and four with microduplication) are reported with 6q26 deletion disrupting the PARK2 gene. Microdeletion sizes ranged between 215 Kb and 356 Kb, and duplication between 279 Kb and 726 Kb. These were present within the exons 7-10. Family follow up with FISH probes revealed paternal inheritance in two cases, maternal in two cases, and de novo origin in one case. Our results support previous studies showing that patients with PARK2 CNVs involving exons 5-12 might be more deleterious and cause a unique syndrome. Comprehensive analysis of additional case studies is needed to have a full characterization of this neurological disorder syndrome.

UNASSIGNED: A prospective study using array CGH in children with Syndromic microcephaly from a tertiary pediatric healthcare centre in India.
UNASSIGNED: To identify the copy number variations causative of microcephaly detected through chromosomal array CGH.
UNASSIGNED: Of the 60 patients, 33 (55%) males and 27 (45%) females who consulted the Rare Disease Clinic at Department of Pediatrics, SMS Medical College, Jaipur, with developmental delay/facial dysmorphism/congenital anomalies in combination with microcephaly were included.
UNASSIGNED: Children with acquired or non-genetic causes of microcephaly, craniosynostosis, metabolic diseases, known chromosomal aneuploidy such as trisomy 21, 13, and 18 and abnormal karyotype were excluded. The cohort was analyzed by array CGH in order to identify potentially pathogenic copy number variants (CNVs).
UNASSIGNED: Clinically relevant pathogenic or likely pathogenic copy number variations (CNVs) were identified in 20/60 (33.3%) patients, variant of uncertain significance (VOUS) in 4/60 (6.6%) cases and benign CNVs in 3/60 (5%) of total cases. Out of 20 cases with pathogenic CNVs, 12 (60%) patients detected with a deletion, five (25%) patients with duplication and three (15%) patients resulted with a complex chromosomal rearrangement. Twelve cases present CNVs containing genes known to be implicated in microcephaly etiology.
UNASSIGNED: This research highlights the contribution of submicroscopic chromosomal changes in the etiology of microcephaly in combination with developmental delay/facial dysmorphism/congenital anomalies (syndromic microcephaly). Our studies provide more insights into the benefits derived by using array CGH analysis in patients with syndromic microcephaly.