How chromosomal deletions can unmask recessive mutations? Deletions in 10q11.2 associated with CHAT or SLC18A3 mutations lead to congenital myasthenic syndrome.

A congenital myasthenia was suspected in two unrelated children with very similar phenotypes including several episodes of severe dyspnea. Both children had a 10q11.2 deletion revealed by Single Nucleotide Polymorphisms array or by Next Generation Sequencing analysis.

Discovery of a large deletion of KAL1 in 2 deaf brothers.

Objectives: Kallmann syndrome (KS) usually combines an anosmia and a hypogonadotrophic hypogonadism. Hearing impairment was described in a few cases of KS. Our objective is to describe an unusual presentation of KS in 2 cases and to explore the pattern of inheritance in this family.

Array comparative genomic hybridization profiling analysis reveals deoxyribonucleic acid copy number variations associated with premature ovarian failure.

Introduction: Premature ovarian failure (POF) is defined by amenorrhea of at least 4- to 6-month duration, occurring before 40 yr of age, with two FSH levels in the postmenopausal range. Its etiology remains unknown in more than 80% of cases. Standard karyotypes, having a resolution of 5-10 Mb, have identified critical chromosomal regions, mainly located on the long arm of the X chromosome.

Velopharyngoplasty for noncleft velopharyngeal insufficiency: results in relation to 22q11 microdeletion.

Objective: To evaluate the results of velopharyngoplasty for velopharyngeal insufficiency (VPI) in relation to 22q11 deletion or nonsyndromic VPI.

Design: Retrospective study.

Setting: Academic medical center.

Atypical deletion of 22q11.2: detection using the FISH TBX1 probe and molecular characterization with high-density SNP arrays.

Despite the heterogeneous clinical presentations, the majority of patients with 22q11.2 deletion syndrome (22q11.2 DS) have either a common recurrent 3 Mb deletion or a less common, 1.

Microduplication 22q11.2: a new chromosomal syndrome.

The chromosome 22q11.2 region has long been implicated in genomic diseases. The low-copy repeats spanning the region predispose to homologous recombination events, and mediate nonallelic homologous recombinations that result in rearrangements of 22q11.

Fertility defects revealing germline biallelic nonsense NBN mutations.

Biallelic mutations in the NBN/NBS1 gene are the cause of Nijmegen breakage syndrome (NBS), a severe pediatric disease characterized by dysmorphy with a bird-like face, microcephaly, growth retardation, immune deficiency, and proneness to cancer. We here report two adult siblings that are compound heterozygotes for two previously unreported NBN nonsense mutations. These patients presented with the unique clinical symptom of fertility defects.

Myoclonus-dystonia due to maternal uniparental disomy.

Background: Myoclonus-dystonia is a movement disorder often associated with mutations in the maternally imprinted epsilon-sarcoglycan (SGCE) gene located on chromosome 7q21. Silver-Russell syndrome is a heterogeneous disorder characterized by prenatal and postnatal growth restriction and a characteristic facies, caused in some cases by maternal uniparental disomy of chromosome 7.

Objectives: To describe and investigate the combination of a typical myoclonus-dystonia syndrome and Silver-Russell syndrome.

Mechanisms of genesis of variant translocation in chronic myeloid leukemia are not correlated with ABL1 or BCR deletion status or response to imatinib therapy.

Many published studies have indicated that various mechanisms could be involved in the genesis of variant chronic myelogeneous leukemia (CML) translocations. These are mainly one-step or two-step mechanisms, associated or not with deletions adjacent to the translocation junction on der(9) or der(22) chromosomes (or both). Based on the mechanism of genesis, it has been suggested that the complexity may affect the occurrence of ABL1 and BCR deletions (either or both), or may be associated with the CML disease course, and thus could determine the response to imatinib therapy.

Beckwith-Wiedemann-like macroglossia and 18q23 haploinsufficiency.

Beckwith-Wiedemann syndrome (BWS) is an overgrowth condition with tumor proclivity linked to a genetic imbalance of a complex imprinted region in 11p15.5. A female child with features fitting in with the BWS diagnostic framework and an apparent loss of imprinting (LOI) of the IGF2 gene in 11p15.

Cryptic Xp duplication including the SHOX gene in a woman with 46,X, del(X)(q21.31) and premature ovarian failure.

Background: Premature ovarian failure (POF) is defined as amenorrhoea for >6 months, occurring before the age of 40, with an FSH serum level in the menopausal range. Although Xq deletions have been known for a long time to be associated with POF, the mechanisms involved in X deletions in order to explain ovarian failure remain unknown. In order to look for potentially cryptic chromosomal imbalance, we used high-resolution genomic analysis to characterize X chromosome deletions associated with POF.

Recurrent inverted duplication of 2p with terminal deletion in a patient with the classical phenotype of trisomy 2p23-pter.

Inverted duplications with terminal deletions have been reported in an increasing number of chromosomes and are probably more frequent than suspected until recently. We describe the cytogenetic and molecular characterization of an inverted duplication of chromosome 2p in an 8-year-old girl. Firstly interpreted as partial duplication 2p, the rearrangement was in fact an inverted duplication associated with a terminal deletion of the short arm of the rearranged chromosome 2, the latter not being detectable by cytogenetic analysis.

Midline defects in deletion 18p syndrome: clinical and molecular characterization of three patients.

The phenotype of monosomy 18p varies widely, the main clinical manifestations being mental and growth retardation, and craniofacial dysmorphism. Clinical features also include growth hormone (GH) deficiency, or holoprosencephaly (HPE). Haploinsufficiency for TGIF, mapped to 18p11.

Heterogeneity of NSD1 alterations in 116 patients with Sotos syndrome.

Sotos syndrome is an overgrowth syndrome characterized by distinctive facial features, learning difficulties, and macrocephaly with frequent pre- and postnatal overgrowth with advanced bone age. Here, we report on our experience in the molecular diagnostic of Sotos syndrome on 116 patients. Using direct sequencing and a quantitative multiplex PCR of short fluorescent fragments (QMPSF)-based assay allowing accurate detection of both total and partial NSD1 deletions, we identified NSD1 abnormalities in 104 patients corresponding to 102 Sotos families (90%).