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Results for “Microdeletion”

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At least 397 records · Page 22Linked to original sources
PubMed2006

A microdeletion in Xp11.3 accounts for co-segregation of retinitis pigmentosa and mental retardation in a large kindred.

In a previous report, Aldred et al. [1994] described a 5-generation family in which severe retinitis pigmentosa (RP) co-segregates with mild-moderate mental retardation as an X-linked recessive phenotype mapping to the broad interval between Xp21-q21. We re-examined this family, initially analyzing RP2, a gene in the disease interval that was identified as a cause of RP after the initial report of this family. We found that the male propositus lacked the 5' three exons of RP2 and that RP2 marks the centromeric boundary of a 1.27 Mb deletion that includes two other annotated genes (SLC9A7, CHST7), one predicted transcript encoding a zinc finger protein (FLJ20344) and two highly conserved miRNAs (mir221, mir222). We conclude that this family is segregating a contiguous gene deletion and that the absence of a functional RP2 accounts, at least in part, for the retinal degeneration while deletion of one or more of the other genes is likely responsible for the mental retardation phenotype.

Antiporters↗
PubMed2006

Major feeding difficulties in the first reported case of interstitial 20q11.22-q12 microdeletion and molecular cytogenetic characterization.

We report on a 4-year-old female presenting with intrauterine growth retardation, facial dysmorphic features, major feeding difficulties with severe diarrhea and vomiting, mental retardation with abnormal behavior and hypertonia. Feeding difficulties were the most invalidating features with absent oral intake requiring persistent enteral feeding. Standard cytogenetic studies were normal, but high-resolution chromosome analyses revealed a small de novo interstitial deletion of the long arm of chromosome 20, 46,XX,del(20)(q11.21q12). The deletion was confirmed using metaphase comparative genomic hybridization (CGH) and multicolor high resolution banding (mBAND). The deletion breakpoints were characterized using FISH analyses with YACs, PACs, and BACs clones located in the deleted and adjacent regions. A 6.6-Mb deleted region between markers D20S815 (20q11.22) and D20S435 (20q12) could be delineated. None of the nine previously reported cases with interstitial 20q deletion found in the literature involve the same breakpoints. This report further emphasizes the indication of high-resolution chromosome analyses in children with syndromic mental retardation. The description of additional cases would be useful in order to better characterize the phenotype of patients with proximal interstitial 20q deletion.

Abnormalities, Multiple↗
PubMed2026

De Novo 2.2 Mb 19q13.42-q13.43 Microdeletion Encompassing U2AF2: Support for a Haploinsufficiency Model.

U2 small nuclear RNA auxiliary factor 2 (U2AF2) is an essential pre-mRNA splicing factor involved in the early stages of pre-mRNA splicing. To date, multiple individuals have been reported with predominantly heterozygous missense variants presenting intellectual disability, speech and motor delays, seizures, hypotonia, and thin or hypoplastic corpus callosum. Here, we describe a patient with a de novo 2.2 Mb interstitial deletion involving chromosome 19q13.42-q13.43, encompassing U2AF2, presenting with intellectual disability, epilepsy, corpus callosum hypoplasia, dysmorphic features, and congenital heart disease. The patient's clinical features overlap substantially with those reported in individuals harboring heterozygous U2AF2 variants, supporting haploinsufficiency as a plausible disease mechanism. To our knowledge, this represents the first postnatal report of complete U2AF2 gene deletion. In addition, this is the first detailed phenotypic characterization of a distal 19q chromosomal interstitial deletion, further delineating the clinical spectrum associated with this genomic region.

Humans↗
PubMed2002

Identification of seven novel missense mutations, two splice-site mutations, two microdeletions and a polymorphic amino acid substitution in the gene for ornithine transcarbamylase (OTC) in patients with OTC deficiency.

Ornithine transcarbamylase (OTC) deficiency, a X-linked disorder, is the most frequent inborn error of the urea cycle. Point mutations and small deletions/insertions in the OTC gene are responsible for the majority of the cases and have a "private" character with little recurrence. We report on eleven pathological changes in the OTC gene sequence detected in three males with mild clinical presentations, and in eight symptomatic females. All of these mutations are novel. Only one mutation affects a CpG mutational hot spot, whereas all but one of the mutations caused an abnormal SSCP of the corresponding PCR-amplified exon. Two mutations occurring in females involved one or two base deletions in codons 196 and 330, respectively, causing frameshift changes and premature termination. Another two mutations in a female and a male affected acceptor splice sites at bases -1 and -3 of the intron 6/exon 7 and intron 9/exon 10 junctions, respectively. All other mutations were point changes causing the simple amino acid substitutions (M1I, I160S, L191F, M206I, L301F, P305H and L341P), although the mutation M1I may abolish translation of the OTC polypeptide. This mutation coexisted in a female patient with the change T333A that appears to be a previously unreported polymorphism. The three male patients but only four of the eight female patients inherited the mutation.

Adult↗
PubMed2006

Identification of the microdeletion breakpoint in a GLRA1null allele of Turkish hyperekplexia patients.

Hyperekplexia (startle disease) is a hereditary motor disease caused by mutations within the GLRA1 gene (Chr. 5q33.1), which encodes the alpha1 subunit of the inhibitory glycine receptor (GlyR). While most patients are diagnosed with dominant hyperekplexia associated with point mutations within or adjacent to the channel pore, recessive hyperekplexia is less frequent. Here, we report five new pedigrees of recessive hyperekplexia in apparently unrelated families of Kurdish origin associated with a deletion of exons 1-7 of the GLRA1 gene. The deletion was identical in all families, encompassing 329 Kb of genomic sequence. No other known functional genes were involved, indicating that the GLRA1null allele is distinct from the 5q syndrome. Analysis of the DNA sequence flanking the proximal and distal breakpoint revealed no significant homology of sequences immediately adjacent to the breaks. Consensus sites for Toposiomerase II were detected close to the breakpoint compatible with an illegitimate recombination event. No heterozygous carriers of the deletion allele were detected by screening of 500 individuals from the southeastern Mediterranean region belonging to four different ethnic groups. Hence, the identical nature of the breakpoint junction in all patients and carriers suggests a founder mutation in an ethnic population originating from Turkey.

Alleles↗
PubMed1994

IL-2R gamma gene microdeletion demonstrates that canine X-linked severe combined immunodeficiency is a homologue of the human disease.

X-linked severe combined immunodeficiency (SCID) is characterized by profound defects in cellular and humoral immunity and, in humans, is associated with mutations in the gene for the gamma chain of the IL-2 receptor (IL-2R gamma). We have examined this gene in a colony of dogs established from a single X-linked SCID carrier female. Affected dogs have a 4-bp deletion in the first exon of the IL-2R gamma gene, which precludes the production of a functional protein, demonstrating that the canine disease is a true homologue of human X-linked SCID.

Amino Acid Sequence↗
PubMed1998

A microdeletion of D6S305 in a family of autosomal recessive juvenile parkinsonism (PARK2).

A gene for autosomal recessive juvenile parkinsonism (ARJP; HGMW-approved symbol PARK2; MIM 600116) has recently been mapped to a 17-cM interval on chromosome 6q25.2-q27. We here report an inbred family with ARJP showing a perfect cosegregation with null allele for D6S305, which is a marker within the ARJP locus. We assigned the deletion within an interval between D6S1937 and AFMa155td9, which are 0 cM apart from each other and located on a single YAC clone. Two possibilities should be evaluated: (1) the deletion is polymorphic and linked to ARJP and (2) the deletion is pathogenic and contains both D6S305 and the ARJP gene (or a part of it). An exon search in a deleted segment or in the relatively small-sized genomic clones harboring D6S305 may enormously facilitate the cloning procedure of the ARJP gene.

Chromosome Deletion↗
PubMed1986

De novo DNA microdeletion in a girl with Turner syndrome and Duchenne muscular dystrophy.

The single X chromosome of a girl with Turner syndrome (45,X) and typical Duchenne muscular dystrophy was investigated at the chromosomal and DNA levels. No visible abnormality of the residual X chromosome was found upon high-resolution R-banding. The DNA was analysed by Southern blotting and hybridization with seven cloned probes mapping in the Xp21 region where the Duchenne locus is thought to be located. A molecular deletion was detected with probes pERT 87.1, pERT 87.8, and pERT 87.15. The other probes (754, C7, 99.6, and RC8) gave a normal signal. The DNA alleles seen in the two parents indicated that the deletion found in the propositus had occurred de novo on a maternal X chromosome.

Adolescent↗
PubMed1988

Xp21 DNA microdeletion in a patient with chronic granulomatous disease, retinitis pigmentosa, and McLeod phenotype.

The clinical, biochemical, and molecular analysis of a patient with chronic granulomatous disease (CGD), retinitis pigmentosa (RP), and McLeod phenotype and of his parents demonstrated the X-linked transmission of these three traits in this family and a deletion of the entire X-CGD gene of the patient DNA. All but one other DNA markers tested, including those in Xp21, were present. These findings strongly suggest that the McLeod locus and at least one XL RP gene are closely linked to the X-CGD locus in the Xp21 region of the human X chromosome.

Child, Preschool↗