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)

Microcephalin (MCPH1) is identified as being responsible for the neurodevelopmental disorder primary microcephaly type 1, which is characterized by a smaller-than-normal brain size and mental retardation. MCPH1 has originally been identified as an important regulator of telomere integrity and of cell cycle control. Genetic and cellular studies show that MCPH1 controls neurogenesis by coordinating the cell cycle and the centrosome cycle and thereby regulating the division mode of neuroprogenitors to prevent the exhaustion of the progenitor pool and thereby microcephaly. In addition to its role in neurogenesis, MCPH1 plays a role in gonad development. MCPH1 also functions as a tumor suppressor in several human cancers as well as in mouse models. Here, we review the role of MCPH1 in DNA damage response, cell cycle control, chromosome condensation and chromatin remodeling. We also summarize the studies on the biological functions of MCPH1 in brain size determination and in pathologies, including infertility and cancer.
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PMID:The DNA damage response molecule MCPH1 in brain development and beyond. 2719 93

Human hearing loss is a common neurosensory disorder about which many basic research and clinically relevant questions are unresolved. This review on hereditary deafness focuses on three examples considered at first glance to be uncomplicated, however, upon inspection, are enigmatic and ripe for future research efforts. The three examples of clinical and genetic complexities are drawn from studies of (i) Pendred syndrome/DFNB4 (PDS, OMIM 274600), (ii) Perrault syndrome (deafness and infertility) due to mutations of CLPP (PRTLS3, OMIM 614129), and (iii) the unexplained extensive clinical variability associated with TBC1D24 mutations. At present, it is unknown how different mutations of TBC1D24 cause non-syndromic deafness (DFNB86, OMIM 614617), epilepsy (OMIM 605021), epilepsy with deafness, or DOORS syndrome (OMIM 220500) that is characterized by deafness, onychodystrophy (alteration of toenail or fingernail morphology), osteodystrophy (defective development of bone), mental retardation, and seizures. A comprehensive understanding of the multifaceted roles of each gene associated with human deafness is expected to provide future opportunities for restoration as well as preservation of normal hearing.
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PMID:Unresolved questions regarding human hereditary deafness. 2725 78

Loss-of-function DCAF17 variants cause hypogonadism, partial alopecia, diabetes mellitus, mental retardation, and deafness with variable clinical presentation. DCAF17 pathogenic variants have been largely reported in the Middle Eastern populations, but the incidence in American families is rare and animal models are lacking. Exome sequencing in 5 women with syndromic hypergonadotropic hypogonadism from 2 unrelated families revealed novel pathogenic variants in the DCAF17 gene. DCAF17 exon 2 (c.127-1G > C) novel homozygous variants were discovered in 4 Turkish siblings, while 1 American was compound heterozygous for 1-stop gain variant in exon 5 (c.C535T; p.Gln179*) and previously described stop gain variant in exon 9 (c.G906A; p.Trp302*). A mouse model mimicking loss of function in exon 2 of Dcaf17 was generated using CRISPR/Cas9 and showed female subfertility and male infertility. Our results identify 2 novel variants, and show that Dcaf17 plays a significant role in mammalian gonadal development and infertility.
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PMID:Novel inactivating mutations of the DCAF17 gene in American and Turkish families cause male infertility and female subfertility in the mouse model. 2917 22

Thyroid hormones are vital for the proper functioning of the female reproductive system, since they modulate the metabolism and development of ovarian, uterine, and placental tissues. Therefore, hypo- and hyperthyroidism may result in subfertility or infertility in both women and animals. Other well-documented sequelae of maternal thyroid dysfunctions include menstrual/estral irregularity, anovulation, abortion, preterm delivery, preeclampsia, intrauterine growth restriction, postpartum thyroiditis, and mental retardation in children. Several studies have been carried out involving prospective and retrospective studies of women with thyroid dysfunction, as well as in vivo and in vitro assays of hypo- and hyperthyroidism using experimental animal models and/or ovarian, uterine, and placental cell culture. These studies have sought to elucidate the mechanisms by which thyroid hormones influence reproduction to better understand the physiology of the reproductive system and to provide better therapeutic tools for reproductive dysfunctions that originate from thyroid dysfunctions. Therefore, this review aims to summarize and update the available information related to the role of thyroid hormones in the morphophysiology of the ovary, uterus, and placenta in women and animals and the effects of hypo- and hyperthyroidism on the female reproductive system.
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PMID:Thyroid hormones and female reproduction. 2976 91

Bardet-Biedl syndrome (BBS) is an autosomal recessive disease with a prevalence of about 1/125,000. The syndrome involves mixed rod-cone dystrophy (which becomes obvious by 6 years of age). About two thirds of patients have postaxial polydactyly, and sometimes syndactyly, brachydactyly, and/or clinodactyly may be present. Hypogonadism and renal involvement occur in about 40%, mental retardation in about 50%, and truncal obesity in about 70%; it is present early, along with insulin resistance, type 2 diabetes, dyslipidemia, and hypertension. Vision becomes markedly impaired by about age 30 years. The BBS is genetically heterogeneous entity with considerable phenotypic variability. Other associated problems include CNS-related ataxia, abnormal gait, and facial hypotonia, as well as anomalies such as high palate, hearing loss, and cardiac malformations. In males, there is oligospermia, leading to infertility. Around 50–80% of BBS patients have renal malformations (like cyst, agenesis or scarring) and renal dysfunction leading to end-stage renal disease. There are no pigmentary changes before the age of 1–2 years. Later, subtle pigmentary changes appear in the macula or peripapillary area. Several years later, pigments appear in the equatorial region, along with attenuation of retinal blood vessels and waxy pallor of the optic disc. Eventually, the macula may show atrophic changes (Figs. 33.1, 33.2 and 33.3). Electroretinography (ERG) shows involvement of rods and cones and is abnormal even before the fundus shows changes. A perimacular hyperfluorescent ring can be seen.
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PMID:Ciliopathy: Bardet-Biedl Syndrome. 3057 6

Monitoring the safety of intracytoplasmic sperm injection (ICSI) has been impeded by uncertainties regarding the extent to which offspring health is influenced by paternal characteristics linked to male infertility or the processes that ICSI treatment entails. Few studies examining long-term health and developmental outcomes in children conceived with ICSI have considered the influence of paternal infertility adequately. In the available literature, large population-based studies suggest underlying male factors, and the severity of male factor infertility, increase the risk of mental retardation and autism in offspring, as does the ICSI procedure itself, but these findings have not been replicated consistently. Robust evidence of the influence of male factors on other health outcomes is lacking, with many studies limited by sample size. Nevertheless, emerging evidence suggests children conceived with ICSI have increased adiposity, particularly girls. Further, young men conceived with ICSI may have impaired spermatogenesis; the mechanisms underlying this remain unclear, with inconclusive evidence of inheritance of Y chromosome microdeletions. The current inconsistent and often sparse literature concerning the long-term health of children conceived with ICSI, and the specific influence of male infertility factors, underscore the need for concerted monitoring of children conceived with this technique across the lifespan. With the rapid expansion of use of ICSI for non-male factors, sufficiently large studies that compare outcomes between groups conceived with this technique for male factors versus non-male factors will provide critical evidence to elucidate the intergenerational impact of male infertility.
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PMID:Impact of male factor infertility on offspring health and development. 3182 14

Small supernumerary marker chromosomes (sSMCs) are defined as structurally abnormal chromosomes that may be detected pre- or postnataly in patients with developmental and/or mental retardation or infertility. sSMC on chromosome 15 accounts for the highest proportion of all sSMCs and may be detected in subfertile individuals. The present study reports the case of a male patient with oligoasthenoteratozoospermia and an sSMC. The sSMC was identified and characterized according to G-banding analysis, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) analysis. Chromosomal karyotype analysis suggested that the patient presented with 47,XY,+mar. CMA was used to characterize the sSMC, which revealed a 0.44-Mb microduplication in 6q25.3q26. Subsequently, FISH using centromere-specific probes for chromosomes 13/21, 14/22 and 15 was applied to identify the origin of the sSMC, which was finally determined to be inverted duplicated(15)(q11.2). It was hypothesized that heterochromatin in the sSMC is responsible for the patient's fertility problem. The presence of heterochromatin may disrupt regular meiosis, thereby affecting normal spermatogenesis. Impaired spermatogenesis in infertile males with an sSMC derived from chromosome 15 was also reviewed by searching published literature and the sSMC database (http://ssmc-tl.com/sSMC.html). For patients with low sperm parameters and complete absence of spermatozoa in the ejaculate, including infertile males with an sSMC with spermatozoa, intracytoplasmic sperm injection is considered as an effective assisted reproductive technique. It may be concluded that molecular cytogenetic techniques are critical tools for delineating sSMCs in infertile males and may be beneficial in identifying sSMC carriers to ensure they receive clinical genetic counseling.
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PMID:Molecular cytogenetic characterization of small supernumerary marker 15 in infertile male: A case report. 3225 78

Klinefelter Syndrome (KS) is the most common aneuploidy in humans (prevalence: 85-250 per 100,000 born males) and is characterized by one or more supernumerary X-chromosomes (47-XXY, 48-XXXY and 49-XXXXY karyotypes). KS is a multisystemic disorder associated to multiple phenotypic features including cardiac abnormalities, infertility, mental retardation, diabetes and increased cancer risk. Using a non-integrative mRNAs reprogramming approach, we generated two iPSC lines 48-XXXY and 49-XXXXY from a non-mosaic 49-XXXXY KS patient carrying a balanced translocation t(4,11) (q35,q23). These iPSC lines provide a unique cellular platform to study the molecular mechanisms underlying KS pathophysiology.
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PMID:Generation of two iPSC lines (KAUSTi001-A, KAUSTi002-A) from a rare high-grade Klinefelter Syndrome patient (49-XXXXY) carrying a balanced translocation t(4,11) (q35,q23). 3325 93


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