Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interstitial 3p21.31 deletions have been very rarely reported. We describe a 7-year-old boy with global developmental delay, specific facial characteristics, hydronephrosis, and hypothyreosis with a de novo deletion of 3p21.31, encompassing 29 OMIM genes. Despite the wide use of microarrays, no similar case has been reported in the literature so far. Five overlapping cases are deposited in the DECIPHER database, 2 of which have significant overlapping chromosomal aberrations. They both share some phenotypic characteristics with our case, e.g. developmental delay, intellectual disability and facial dysmorphism (arched eyebrows, hypertelorism, low-set ears, and a large nose tip). In addition, loss-of-function mutations in the SETD2 gene (OMIM 612778) of the deleted region have been described in 3 patients, presenting with some similar clinical features, namely overgrowth, intellectual disability, speech delay, hypotonia, autism, and epilepsy. Therefore, SETD2 may explain part of the phenotype in our case. We focused on 3 other genes in the deleted region, based on their known functions, namely CSPG5 (OMIM 606775), PTH1R (OMIM 168468) and SMARCC1 (OMIM 601732), and assessed their potentially important role in describing the patient's phenotype. Additional cases with haploinsufficiency of this region are needed to elucidate further genotype-phenotype correlations.
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PMID:A New Case of an Extremely Rare 3p21.31 Interstitial Deletion. 2738 66

We present a 7-year old male with severe delays, hypotonia and dysmorphic features who had striking, deep palmar and plantar creases and pillowing of the soft tissues of the palms and soles. His facial features included a high anterior hairline, small eyes with narrowed palpebral fissures, a bulbous nasal tip with a short columella, and a large mouth with a thin upper vermilion, and small chin. He had a submucous cleft palate, bilateral cryptorchidism and hydronephrosis. Cranial imaging demonstrated an Arnold Chiari malformation that was also present in his maternal uncle by report. Exome sequencing revealed a de novo heterozygous sequence variant, p.Tyr446Cys, in TBL1XR1 that has previously been reported in six patients with Pierpont syndrome. This sequence variant occurs in the carboxy-terminal, WD40 domain of the protein. As TBL1XR1 is a critical component of the NCoR/SMRT co-repressor complex and the WD40 repeats are hypothesized to interact with histone H2B and H4, the mutation may impact protein interactions necessary for stabilizing the complex with chromatin. De novo missense and frameshift mutations and deletions involving TBL1XR1 have been described in patients with intellectual disability and autism, but without any of the dysmorphic findings or malformations associated with Pierpont syndrome, implying a mutation-specific mechanism for the pathogenicity of p.Tyr446Cys. Our case is the first individual with this mutation to have a submucous cleft palate and hydronephrosis, although his severe delays, hypotonia, dysmorphic findings and emerging scoliosis appear consistent with previous reports. His distinctive facial and digital features are further evidence that p.Tyr446Cys results in a clinically recognizable, syndromic form of intellectual disability in contrast to other TBL1XR1 mutations.
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PMID:Pierpont syndrome associated with the p.Tyr446Cys missense mutation in TBL1XR1. 2868 24