Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019270 (hernia)
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We report on two siblings (half brothers on the paternal side) with a syndrome consisting of delayed development, cardiac anomalies, chest deformity, hip rotation, metatarsus adductus, genital hypoplasia, dysmorphic face, depressed nasal bridge, mental retardation, and speech delay. All metaphases examined showed a normal karyotype in the patients, their father, and both mothers. High-resolution array CGH examination revealed a 16q (6 Mb) duplication dup(16)(16q23.3 --> 16qter) and a 5p (0.97 Mb) terminal deletion del(5)(p15.32 --> pter) in both affected boys but not their healthy siblings or parents. Interphase fluorescence in situ hybridization (FISH) confirmed both the 16q duplicated region and the 5p terminal deletion. Clinical abnormalities in the patients included thin upper lip, clinodactyly, and foot deformity, which were reported previously with duplications in 16q23.3. Pectus excavatum, hip rotation, metatarsus adductus, umbilical hernia, brachycephaly, and esotropia were not reported previously in chromosome 16q duplications but may be features that occur intermittently. The 5p deleted region has been associated previously only with speech delay, which was present in both patients. These patients display certain phenotypic characteristics not reported previously in 16q duplication and confirm 5p terminal deletion as an important chromosome anomaly for speech delay.
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PMID:A t(5;16)(p15.32;q23.3) generating 16q23.3 --> qter duplication and 5p15.32 --> pter deletion in two siblings with mental retardation, dysmorphic features, and speech delay. 2050 35

Two siblings, from a consanguineous Iraqi family, were investigated to identify the underlying genetic cause of their high myopia, esotropia, vitreous changes and cataract. Subsequent investigation identified low molecular weight proteinuria as part of their syndrome. Exome sequencing of one of the probands revealed a new non-synonymous variant in the LRP2 gene. Sanger sequencing confirmed the mutation and segregation in the family. No mutation was identified in COL9A1/2, COL11A1/2, or COL2A1 genes. The variant (c.11483A>G; p.Asp3828Gly) is predicted to be damaging and is conserved among vertebrate species. Mutations in LRP2 have been shown to cause the Donnai-Barrow syndrome (DBS) or facio-oculo-acoustico-renal (FOAR) syndrome, a syndrome associated with facial dysmorphism, ocular anomalies, sensorineural hearing loss, low molecular weight proteinuria, and diaphragmatic hernia and absent corpus callosum, although there is variability in the expression of some features. This family shows a milder phenotype with a predominant eye phenotype similar to the Stickler syndrome and only a few features of the DBS, including microglobulinuria. The presence of microglobulinuria was only detected after molecular results were known. In conclusion, with the identification of a new mutation in LRP2 associated with a predominant eye phenotype similar to the Stickler syndrome, we have broadened the phenotypic spectrum of LRP2 mutations.
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PMID:Broadening the phenotype of LRP2 mutations: a new mutation in LRP2 causes a predominantly ocular phenotype suggestive of Stickler syndrome. 2399 33

Autosomal recessive variants in the adenosine deaminase, tRNA specific 3 ( ADAT3 ) gene cause a syndromic form of intellectual disability due to a loss of ADAT3 function. This disorder is characterized by developmental delay, intellectual disability, speech delay, abnormal brain structure, strabismus, microcephaly, and failure to thrive. A small subset of individuals with ADAT3 deficiency have other structural birth defects including atrial septal defect, patent ductus arteriosus, hypospadias, cryptorchidism, and micropenis. Here, we report a sibling pair with novel compound heterozygous missense variants that affect a conserved amino acid in the deaminase domain of ADAT3. These siblings have many of the features characteristic of this syndrome, including, intellectual disability, hypotonia, esotropia, failure to thrive, and microcephaly. Both had gastroesophageal reflux disease (GERD), feeding problems, and aspiration requiring thickening of feeds. Although they have no words, their communication abilities progressed rapidly when they began to use augmentative and alternative communication (AAC) devices. One of these siblings was born with an anterior congenital diaphragmatic hernia, which has not been reported previously in association with ADAT3 deficiency. We conclude that individuals with ADAT3 deficiency should be monitored for GERD, feeding problems, and aspiration in infancy. They may also benefit from the use of AAC devices and individualized educational programs that take into account their capacity for nonverbal language development. Additional studies in humans or animal models will be needed to determine if ADAT3 deficiency predisposes to the development of structural birth defects.
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PMID:Novel Missense Variants in ADAT3 as a Cause of Syndromic Intellectual Disability. 3168 66