14 research outputs found
Deletions of the homeobox gene SHOX (short stature homeobox) are an important cause of growth failure in children with short stature
Short stature, with an incidence of 3 in 100, is a fairly frequent
disorder in children. Idiopathic short stature refers to patients who
are short due to various unknown reasons. Mutations of a human homeobox
gene, SHOX (short stature homeobox), have recently been shown to be
associated with the short stature phenotype in patients with Turner
syndrome and most patients with Leri-Weill dyschondrosteosis. This study
addresses the question of the incidence and type of SHOX mutations in
patients with short stature. We analyzed the SHOX gene for intragenic
mutations by single strand conformation polymorphism, followed by
sequencing, in 750 patients and for complete gene deletions by
fluorescence in situ hybridization in 150 patients (total, 900
patients). This is the largest group of patients with short stature
studied to date for SHOX mutations. All patients had a normal karyotype,
and their height for chronological age were below the third percentile
or minus 2 SD of national height standards. All were without obvious
skeletal features reminiscent of the Leri-Weill syndrome at the time of
diagnosis.
Silent, missense, and nonsense mutations and a small deletion in the
coding region of SHOX were identified in 9 of the 750 patients analyzed
for intragenic mutations. Complete gene deletions were detected in 3 of
the 150 patients studied for gene deletions. At least 3 of the 9
intragenic mutations were judged to be functional based upon the
genotype-phenotype relationship for the parents and normal control
individuals. We conclude that SHOX mutations have been detected in 2.4%
of children with short stature. The spectrum of SHOX mutations is
biased, with the vast majority leading to complete gene deletions. The
prevalence of short stature due to SHOX gene mutations among children
with short stature appears to be similar to that of GH deficiency or
Turner syndrome. Family studies of the children with SHOX mutations
often reveal older family members with same mutation who exhibit mild
skeletal features reminiscent of the Turner syndrome, such as
high-arched palate, short neck, abnormal auricular development, cubitus
valgus, genu valgum, short fourth metacarpals, and Madelung deformity
Deletions of the homeobox gene SHOX (short stature homeobox) are an important cause of growth failure in children with short stature
Short stature, with an incidence of 3 in 100, is a fairly frequent disorder in children. Idiopathic short stature refers to patients who are short due to various unknown reasons. Mutations of a human homeobox gene, SHOX (short stature homeobox), have recently been shown to be associated with the short stature phenotype in patients with Turner syndrome and most patients with Léri-Weill dyschondrosteosis. This study addresses the question of the incidence and type of SHOX mutations in patients with short stature. We analyzed the SHOX gene for intragenic mutations by single strand conformation polymorphism, followed by sequencing, in 750 patients and for complete gene deletions by fluorescence in situ hybridization in 150 patients (total, 900 patients). This is the largest group of patients with short stature studied to date for SHOX mutations. All patients had a normal karyotype, and their height for chronological age were below the third percentile or minus 2 SD of national height standards. All were without obvious skeletal features reminiscent of the Leri-Weill syndrome at the time of diagnosis. Silent, missense, and nonsense mutations and a small deletion in the coding region of SHOX were identified in 9 of the 750 patients analyzed for intragenic mutations. Complete gene deletions were detected in 3 of the 150 patients studied for gene deletions. At least 3 of the 9 intragenic mutations were judged to be functional based upon the genotype-phenotype relationship for the parents and normal control individuals. We conclude that SHOX mutations have been detected in 2.4% of children with short stature. The spectrum of SHOX mutations is biased, with the vast majority leading to complete gene deletions. The prevalence of short stature due to SHOX gene mutations among children with short stature appears to be similar to that of GH deficiency or Turner syndrome. Family studies of the children with SHOX mutations often reveal older family members with same mutation who exhibit mild skeletal features reminiscent of the Turner syndrome, such as high-arched palate, short neck, abnormal auricular development, cubitus valgus, genu valgum, short fourth metacarpals, and Madelung deformity
Clinical Case Seminar in Pediatric Thyroid Disease
Pediatric thyroid diseases cover a large spectrum of congenital and acquired forms, ranging from congenital primary or central hypothyroidism, autoimmune thyroid disease, iodine deficiency, rare genetic defects of thyroid hormone action, metabolism and cell membrane transport to benign nodules and malignant tumors. The previous 15 papers of the textbook Paediatric Thyroidology gave a systematic overview of the current knowledge and guidelines on all these diseases. In this final paper, the authors collected a series of patient histories from their clinics illustrating frequently encountered clinical problems and providing key learning points and references to each case. Although not fully comprehensive, it aims at providing relevant clinical knowledge on thyroid diseases of the neonate, the child, and the adolescent