BACKGROUND: Chromosomal microarray analysis is an essential tool for copy number variants detection in patients with unexplained developmental delay/intellectual disability, autism spectrum disorders, and multiple congenital anomalies. The study aims to determine the clinical significance of chromosomal microarray analysis in this patient group. Another crucial aspect is the evaluation of copy number variants detected in terms of the diagnosis of patients. METHODS AND RESULTS: A Chromosomal microarray analysis was was conducted on a total of 1227 patients and phenotype-associated etiological diagnosis was established in 135 patients. Phenotype-associated copy number variants were detected in 11% of patients. Among these, 77 patients 77 (57%, 77/135) were diagnosed with well-recognized genetic syndromes and phenotype-associated copy number variants were found in 58 patients (42.9%, 58/135). The study was designed to collect data of patients in Kocaeli Derince Training and Research Hospital retrospectively. In our study, we examined 135 cases with clinically significant copy number variability among all patients. CONCLUSIONS: In this study, chromosomal microarray analysis revealed pathogenic de novo copy number variants with new clinical features. Chromosomal microarray analysis in the Turkish population has been reported in the largest patient cohort to date.
Abnormalities, Multiple , Autism Spectrum Disorder , DNA Copy Number Variations , Developmental Disabilities , Humans , Autism Spectrum Disorder/genetics , Autism Spectrum Disorder/diagnosis , Turkey/epidemiology , DNA Copy Number Variations/genetics , Female , Male , Child , Child, Preschool , Developmental Disabilities/genetics , Developmental Disabilities/diagnosis , Abnormalities, Multiple/genetics , Abnormalities, Multiple/diagnosis , Adolescent , Phenotype , Infant , Intellectual Disability/genetics , Intellectual Disability/diagnosis , Chromosome Aberrations , Microarray Analysis/methods , Retrospective Studies , Adult
Warburg micro (WARBM) syndrome is an autosomal recessive disease characterized by severe brain and eye abnormalities. Loss-of-function mutations in RAB18, RAB3GAP2, RAB3GAP1, or TBC1D20 can lead to this disease. Here, we present two unrelated WARBM syndrome patients who had an RAB3GAP1 c.559 C > T, (p.Arg187Ter) and c.520 C > T (p.Arg174Ter) homozygous state. Both patients had microcephaly, microphthalmia, microcornea, bilateral congenital cataracts, severe intellectual disability, and congenital hypotonia. Using the method of next-generation sequencing and sanger sequencing, we found two nonsense variations at the splice site in exon 7 of RAB3GAP1 in the WARBM syndrome patients. The mutations were predicted to cause the syndrome due to the early stop codon, and the patients had the WARBM1 syndrome. We present the first clinical report of two different unreported variants with RAB3GAP1 mutation in the literature.
BRCA1/2 mutations play a significant role in cancer pathogenesis and predisposition particularly in breast, ovarian and prostate cancers. Thus, germline analysis of BRCA1 and BRCA2 is essential for clinical management strategies aiming at the identification of recurrent and novel mutations that could be used as a first screening approach. We analyzed germline variants of BRCA1/2 genes for 2168 individuals who had cancer diagnosis or high risk assessment due to BRCAs related cancers, referred to 10 health care centers distributed across 7 regions covering the Turkish landscape. Overall, 68 and 157 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-two novel variants were reported from both genes while BRCA2 showed higher mutational heterogeneity. We herein report the collective data as BRCA Turkish consortium that confirm the molecular heterogeneity in BRCAs among Turkish population, and also as the first study presenting the both geographical, demographical and gene based landscape of all recurrent and novel mutations which some might be a founder effect in comparison to global databases. This wider perspective leads to the most accurate variant interpretations which pave the way for the more precise and efficient management affecting the clinical and molecular aspects.
Breast Neoplasms , Ovarian Neoplasms , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/genetics , Female , Genes, BRCA2 , Genetic Predisposition to Disease , Germ Cells/pathology , Germ-Line Mutation , Humans , Male , Ovarian Neoplasms/genetics , Turkey
As a multisystemic congenital mental retardation disorder/anomaly, Smith-Magenis syndrome (SMS) is commonly aroused from de novo interstitial deletion of the 17p11.2 chromosome. The deletion of this chromosome results with haploinsufficiency for the retinoic acid-induced 1 ( RAI1 ) gene. In this article, we present three cases, who were diagnosed with SMS with mental retardation and behavioral problems such as self-hugging and sleeping disturbances. During the evaluation of the patients, it has been found that there was a 3.4-Mb deletion in the 17p11.2 chromosome region of these patients. This deletion includes RAI1 that is a critically involved gene in SMS.
Congenital glycosylation disorders (CDG) are a group of rare hereditary metabolic diseases that result from abnormal protein and lipid glycosylation. Virtually all organ systems can be affected, and neurological involvement is particularly severe and disabling. More than 100 CDG types have been reported to date and those numbers are rapidly increasing. Each type is very rare, and the clinical characteristics of each subtype are difficult to determine. There are large numbers of biochemically unresolved cases defined as CDGIx. In this report, we present a 5-year-old boy who had dysmorphic features, hypotonia, developmental and mental delay, epileptic spasms, recurrent apnea and respiratory failure that led to the diagnosis of an unreported mutation of a rare form of CDG-Ix. This mutation in the STT3B gene affects the catalytic subunit of the oligosaccharyltransferase and the recipient substrate properties, which in part have the same functions in N-glycosylation. A novel homozygous mutation in the STT3B presence of c.38C > G that encodes p.S13W (p.Ser13Trp) was detected with next generation sequencing. The CDG clinical spectrum can be unusual, ranging from dysfunction of certain organs to severe multiple system disorders. Respiratory failure has rarely been reported in these cases. Increased types and numbers of patients constitute symptom variety. The identification of new genes and genotype-phenotype relationships may expand the family of CDG.
Congenital Disorders of Glycosylation , Hexosyltransferases , Respiratory Insufficiency , Child, Preschool , Congenital Disorders of Glycosylation/complications , Congenital Disorders of Glycosylation/diagnosis , Congenital Disorders of Glycosylation/genetics , Glycosylation , Homozygote , Humans , Male , Membrane Proteins , Mutation
BACKGROUND: 14q duplications caused by parental pericentric inversion of chromosome 14 are rarely reported and no clear genotype-phenotype correlation has been determined yet. CASE PRESENTATION: Here we reported a 7 years old female patient with recombinant chromosome characterized by 14 q duplication and originated from maternal pericentric inversion of chromosome 14. Principal clinical findings of the child include developmental delay, microcephaly, hypertelorism, low set ears, clinodactyly of fifth fingers, hypotonia, telecanthus and cardiac malformation. CONCLUSIONS: Her final karyotype was 46,XX,rec(14)dup(14q)inv(14)(p11.2q24)mat,arr14q24.1-qter(64,800,000-108,350,000 bp)x3.
