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45,X/46,XY chromosomal mosaicism presents a range of clinical manifestations, including phenotypes from Turner syndrome through genital abnormalities to apparently unaffected phenotypic males; however, the full clinical spectrum has not yet been fully delineated since prior studies on the clinical phenotype and associated risk of gonadal tumors included small cohorts and limited follow-up. To better describe the clinical manifestations and long-term outcome of patients with 45,X/46,XY mosaicism. We conducted a retrospective chart review of patients with 45,X/46,XY from three health centers (Hospital for Sick Children and Mount Sinai Hospital in Canada, and University of Pittsburgh Medical Center in United States). Of 100 patients with 45,X/46,XY karyotype, 47 were raised as females and 53 as males. Females were significantly shorter than males (p = 0.04) and height Z-score was significantly decreased with age for both genders (p = 0.02). Growth hormone (GH) treatment did not result in a significant height increase compared to the untreated group (p = 0.5). All females required puberty induction in contrast to majority of males. Five females were diagnosed with gonadal tumors, while no males were affected. Around 58% of patients exhibited at least one Turner syndrome stigmata. This study expands the clinical spectrum, long-term outcomes, and associated tumor risk in a large cohort of patients with 45,X/46,XY mosaicism. Additionally, it highlights our experience with GH therapy and prophylactic gonadectomy., (© 2023 Wiley Periodicals LLC.)

We report on a girl with a de novo mosaic derivative chromosome 17 involving a 7.4 Mb deletion of chromosome region 17p11.2 to 17p12 and a duplication of a 12.35 Mb region at 17q22 to 17q24. She was ascertained because of developmental delay, peripheral neuropathy, brachydactyly and minor anomalies. The derivative chromosome was present in approximately 12% of lymphocytes based on FISH studies, and was detected by array comparative genomic hybridization. To our knowledge, this is the third case of mosaicism involving deletion of the 17p11.2 region and the lowest level of mosaicism reported in a patient with Smith-Magenis syndrome (SMS)., (© 2013 Wiley Periodicals, Inc.)

Schimke immuno-osseous dysplasia (SIOD) is a multisystemic disorder with prominent skeletal, renal, immunological, and ectodermal abnormalities. It is caused by mutations of SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), which encodes a DNA stress response protein. To determine the relationship of this function to the SIOD phenotype, we profiled the cancer prevalence in SIOD and assessed if defects of nucleotide excision repair (NER) and nonhomologous end joining (NHEJ), respectively, explained the ectodermal and immunological features of SIOD. Finally, we determined if Smarcal1(del/del) mice had hypersensitivity to irinotecan (CPT-11), etoposide, and hydroxyurea (HU) and whether exposure to these agents induced features of SIOD. Among 71 SIOD patients, three had non-Hodgkin lymphoma (NHL) and one had osteosarcoma. We did not find evidence of defective NER or NHEJ; however, Smarcal1-deficient mice were hypersensitive to several genotoxic agents. Also, CPT-11, etoposide, and HU caused decreased growth and loss of growth plate chondrocytes. These data, which identify an increased prevalence of NHL in SIOD and confirm hypersensitivity to DNA damaging agents in vivo, provide guidance for the management of SIOD patients., (Copyright © 2012 Wiley Periodicals, Inc.)

Potocki-Lupski syndrome is a genomic disorder caused by duplication of 17p11.2. It is characterized by failure to thrive, intellectual disability, hypotonia, and behavioral difficulties. Structural renal anomalies have been observed in <10% of affected individuals. We present detailed clinical and molecular data on six patients with Potocki-Lupski syndrome, two of whom had renal abnormalities, and investigate the prevalence of kidney abnormalities in the mouse model for the syndrome. In contrast to affected humans, the mouse model does not demonstrate a renal phenotype. Comparison of the duplicated segment in patients with Potocki-Lupski syndrome and the renal phenotype and the syntenic duplicated region in the mouse model allowed us to suggest a 0.285 Mb critical region, including the FLCN gene that may be important for development of renal abnormalities in patients with this duplication., (Copyright © 2012 Wiley Periodicals, Inc.)

Interstitial deletions involving 6q11-q14 have been reported in less than 20 patients, with the breakpoints studied by G-banding alone. We report on seven patients with 6q11-q14 interstitial deletions of variable size. The breakpoints were studied by G-banding, dual-color BAC-FISH and SNP array. The results showed the molecular breakpoints differed significantly from the ones obtained from G-banding. The breakpoints studied by BAC-FISH were consistent with the ones from SNP array. Some characteristics from this cohort are consistent with previous reports, but many typical features are lacking in our patients. The cardinal features of 6q11-q14 interstitial deletions in this cohort include: umbilical hernia, hypotonia, short stature, characteristic facial features of upslanting palpebral fissures, low set and/or dysplastic ears, high arched palate, urinary tract anomalies, and skeletal/limb anomalies., (2009 Wiley-Liss, Inc.)