Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chromosomal imbalance of the 17q12 region (which includes the HNF1B transcription factor) has recently emerged as a frequent condition. 17q12 deletion was found in patients with various renal abnormalities, diabetes mellitus (MODY type 5), genital tract or liver test abnormalities, while 17q12 duplication was identified in a subset of patients with autism, mental retardation, epilepsy and/or schizophrenia but no renal disorder. We report here two first-degree relatives carrying a 17q12 duplication and harboring various renal abnormalities (bilateral hypoplastic kidneys with vesico-ureteric reflux or multicystic dysplatic kidney with contralateral hyperechogenic kidney). Esophageal atresia (EA) type C was identified at birth in one patient while none had neurological disorder. Because EA has already been identified in patients with 17q12 duplication or HNF1B point mutation, we screened HNF1B (QMPSF and direct sequencing) in nine additional patients with EA and renal abnormalities but failed to identify any pathogenic variant. This is the second report of HNF1B mutation associated with EA. Moreover, we showed herein, that renal malformations may be part of the 17q12 duplication syndrome.
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PMID:A 17q12 chromosomal duplication associated with renal disease and esophageal atresia. 2154 Jan 30

Maturity-onset diabetes of the young type 2 (MODY2) is a form of monogenic diabetes, characterized by mild fasting hyperglycemia. MODY2 is caused by heterozygous mutations in the GCK gene that encodes the glucokinase enzyme. We describe the clinical features and the underlying genetic defect of MODY2 in a patient with atypical Greig cephalopolysyndactyly syndrome (GCPS). The patient presented with the limb formation and the craniofacial developmental abnormalities typical to GCPS, in addition to mental retardation and epilepsy (assigned as atypical syndrome). Fasting hyperglycemia in the diabetic range, impaired glucose tolerance, and lack of diabetes autoantibodies were compatible with MODY2. In order to delineate the genetic aberrations relevant both to MODY2 and Greig syndrome in this patient, we performed cytogenetic analysis, real-time PCR of the GCK gene, and comparative genomic hybridization (CGH) array. Cytogenetic study has shown a microscopic detectable deletion in the 7p13-15 chromosomal region. Real-time PCR demonstrated a deletion of the GCK gene in the patient but not her parents, and CGH array revealed a deleted region of approximately 12 Mb in the 7p13-15 region. This deleted region included GLI3 and GCK genes (where heterozygous mutations cause GCPS and MODY2, respectively), and many other contiguous genes. Our patient manifests a unique form of MODY2, where GCK gene deletion is part of a large deleted segment in the 7p13-15 chromosomal region.
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PMID:MODY type 2 in Greig cephalopolysyndactyly syndrome (GCPS) as part of a contiguous gene deletion syndrome. 2204 88

Congenital hyperinsulinism is a serious blood glucose regulation defect that interferes with brain development, leading to mental retardation, neurological sequelae and secondary epilepsy and ultimately may be life-threatening. Congenital hyperinsulinism (CHI) is caused by genetic defects of regulation of insulin secretion that induce insulin oversecretion in intrauterine life and postnatally. The clinical consequence is fetal macrosomia and subsequently neonatal and infantile hypoglycaemia. The most severe form is caused by biallelic mutations of KCNJ11 and ABCC8 genes that encode both potassium channel subunits, whereas their heterozygous mutations as well as enzymatic defects (GLUD1, HADH, GCK) lead to milder presentation. HNF4A or HNF1A transcriptional factor defects lead to transient hyperinsulinism but to MODY diabetes later in life, due to biphasic beta-cell dysfunction starting as hyperfunction and developing via normal function to hypofunction. An early aetiological diagnosis and effective treatment of congenital hyperinsulinism substantially improves the outcome regarding not only survival but also neurocognitive functions.Key words: B-cell - congenital hyperinsulinism (CHI) - hypoglycaemia - insulin.
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PMID:[Congenital hyperinsulinism: Loss of B-cell self-control]. 2792 29