OBJECTIVETo study the clinical characteristics and diagnosis of the Johanson-Blizzard syndrome.

METHODThe clinical characteristics and diagnosing procedure of 1 case with Johanson-Blizzard syndrome were analyzed, and genetic analysis was made in diagnosing procedure, and 28 cases of Johanson-Blizzard syndrome with detailed clinical data were reviewed and analyzed.

RESULTA one year and nine months old girl, who was initially admitted to the hospital because of fatty diarrhea and increased frequency of defecation. Imperforate anus, and aplastic alae nasi was noticed after birth. On physical examination, short stature, mental retardation, tooth abnormalities and scalp defects were observed. Fat globule was found by routine stool test. Serum biochemistry showed an exocrine and endocrine pancreatic insufficiency, CT scan of the abdomen demonstrated fatty replacement of the pancreas, UBR1 gene analysis showed heterozygous for two missense changes. In all 29 cases, exocrine pancreatic insufficiency (72.4%) and hypoplasia of the alae nasi (93%) were the most common clinical manifestations, and sensorineural hearing loss (59%), scalp defects (69%) and hair thinning or upsweep of the hair (44.8%), hypothyroidism (44.8%), absence of permanent teeth (44.8%) and imperforate anus (21%) were also very common, but did not include consanguineous marriage of parents (10.3%).

CONCLUSIONJohanson-Blizzard syndrome is a rare autosomal recessive multisystem disorder, it is characterized by the association of congenital exocrine pancreatic insufficiency and hypoplasia or aplasia of the nasal wings, and can be diagnosed by clinical characteristics and UBR1 gene analysis.

Anus, Imperforate ; Deafness ; diagnosis ; genetics ; pathology ; Ectodermal Dysplasia ; diagnosis ; genetics ; pathology ; Female ; Growth Disorders ; Hearing Loss, Sensorineural ; Humans ; Hypothyroidism ; diagnosis ; genetics ; pathology ; Infant ; Intellectual Disability ; Nose ; abnormalities ; pathology ; Pancreatic Diseases ; diagnosis ; genetics ; pathology ; Ubiquitin-Protein Ligases ; genetics

Ring chromosome is a structural abnormality that is thought to be the result of fusion and breakage in the short and long arms of chromosome. Wolf-Hirschhorn syndrome (WHS) is a well-known congenital anomaly in the ring chromosome 4 with a partial deletion of the distal short arm. Here we report a 10-month-old male of mosaic ring chromosome 4 with the chief complaint of severe short stature. He showed the height of -4 standard deviation, subtle hypothyroidism and mild atrial septal defect/ventricular septal defect, and also a mild language developmental delay was suspected. Brain magnetic resonance imaging showed multifocal leukomalacia. Chromosomal analysis of the peripheral blood showed the mosaic karyotype with [46,XY,r(4)(p16q35)[84]/45,XY,-4[9]/91,XXYY, dic r(4;4)(p16q35;p16q35)[5]/46,XY,dic r(4;4)(p16q35;p16q35)[2]]. FISH study showed the deletion of the 4p subtelomeric region with the intact 4q subtelomeric and WHS region. Both paternal and maternal karyotypes were normal. We compared the phenotypic variation with the previously reported cases of ring chromosome 4. The ring chromosome 4 with the subtelomeric deletion of short arm seems to be related with the phenotype of short stature.
*Chromosome Deletion ; *Chromosomes, Human, Pair 4 ; Growth Disorders/*diagnosis/genetics ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Karyotyping ; Male ; *Ring Chromosomes ; Telomere

Distal 15q trisomy or tetrasomy is associated with a characteristic phenotype that includes mild to moderate intellectual disability, abnormal behavior, speech impairment, overgrowth, hyperlaxity, long face, prominent nose, puffy cheeks, pointed chin, small ears, and hand anomalies (mainly arachno- and camptodactyly). We present the case of a 13-yr-old girl with the main clinical features of 15q overgrowth syndrome and a 46,XX,dup(15)(q24q26.3)[117]/46,XX[3].ish dup(15)(q24q26.3) (SNPRN+,PML+,subtel++,tel++) de novo karyotype. The findings in this case are consistent with those in the previous distal 15q trisomy cases that presented with overgrowth and mental retardation. Further, the rearranged chromosome had a double set of directly oriented telomeric and subtelomeric sequences.
Adolescent ; *Chromosome Aberrations ; *Chromosomes, Human, Pair 15 ; Female ; Growth Disorders/diagnosis/*genetics ; Humans ; In Situ Hybridization, Fluorescence ; Mental Retardation/diagnosis/*genetics ; Syndrome ; Telomere/*chemistry

OBJECTIVETo analyze a child with developmental delay, severe mental retardation, speech delay and muscular hypotonia.

METHODSThe karotypes of the child and her parents were analyzed with G-banding analysis. Their genome DNA was also analyzed with array comparative genomic hybridization (array-CGH).

RESULTSNo karyotypic abnormality was detected at cytogenetic level. However, array-CGH has identified a de novo 4q21.21-q22.1 deletion in the child, which has a size of 12.1 Mb.

CONCLUSIONThe de novo interstitial 4q21.21-q22.1 deletion probably underlies the main clinical manifestation in the child. Array-CGH is useful for diagnosing children with multiple congenital anomalies with unclear etiology.

Child, Preschool ; Chromosomes, Human, Pair 4 ; Comparative Genomic Hybridization ; methods ; Female ; Gene Deletion ; Growth Disorders ; diagnosis ; genetics ; Humans ; Intellectual Disability ; diagnosis ; genetics ; Sequence Deletion

OBJECTIVETo summarize the clinical features of idiopathic hypogonadotropic hypogonadism (IHH) diagnosed during childhood, and detect mutations in KAL1 and FGFR1, acting as key clues for diagnoses.

METHODWe collected and analyzed clinical data of 21 cases (including demographic data, chief complaint, history of present illness, family history, physical examination, laboratory tests and imaging studies, etc.) diagnosed with IHH from December 2008 to February 2013. Polymerase chain reaction and gene sequencing was applied to detect mutations on KAL1 and FGFR1. Fifty healthy unrelated individuals were choosen as controls.

RESULTOf 21 patients with IHH, 19 were males and 2 females, they visited us initially from 8-17 years old, with an average of (13.58 ± 2.38) years old. Sixteen cases were KS patients (76%). One boy reported abnormal sense of smelling but having olfactory perfect picture on MRI; 2/19 male cases had no puberty when they were over 13-14 years old without abnormal external genitalia. 8/19 cases only had small penis, 8/19 had both of cryptorchidism and small penis, and the Case 2 also had hypospadias. One boy had cryptorchidism combined with a normal penis. Only 2 girls diagnosed as IHH who visited us because of no puberty signs when they were 13 and 16 years old, respectively. Other clinical manifestations included: one with gynecomastia, 2 had mental retardation, and one was deaf; one with high palatal arch; one with mirror-movement and one with left renal agenesis but normal renal function respectively. Laboratory tests showed that the basic testosterone (T) is low and with inappropriately low or normal gonadotropin hormones. The results of cases of standard human chorionic gonadotropin (HCG) test of 7 cases out of 19 male children's were normal (testosterone>1 100 ng/L), and another nine cases continued to complete the extended HCG test, and the testosterone levels of two of them (cases 6, 8) were still lower than 1 000 ng/L. Family history: the parents in 9/21 family had delayed puberty, involving only one parent in 6 families, involving both in 2 families and the other one was an uncle having micropenis with a child. Among these 21 cases, only one boy's father had hyposmia and his first emission age was 14-15 years. Eleven patients accompanied abnormal sense of smelling and the olfactory organ abnormalities on MRI, 4 had olfactory organ abnormalities on MRI while they had good smelling function self-reportedly. We got 15 samples (12 KS and 3 nIHH cases) to screen the mutation of KAL1 (14 exons) and FGFR1 (18 exons). A splicing mutation c.1062+1G>A in KAL1 is identified in case 17 with IHH. One novel heterozygous FGFR1 mutation, a single base deletion mutation on the exon 1 c.27delC is identified in case 14. This mutation causes the premature termination codons.

CONCLUSIONThis pilot research showed that IHH/KS diagnosis in children depends on clinical manifestation rather than gene analysis. Small penis or cryptorchidism, smelling abnormality and positive familial history may contribute to the KS/HH diagnosis. MRI of olfactory bulb acts as important proof for diagnosis of KS. Mutations in KAL1 and FGFR1 gene are not main causes of Kallmann syndrome.

Adolescent ; Child ; DNA Mutational Analysis ; Exons ; genetics ; Extracellular Matrix Proteins ; genetics ; Female ; Heterozygote ; Humans ; Hypogonadism ; diagnosis ; genetics ; Kallmann Syndrome ; genetics ; Male ; Mutation ; genetics ; Nerve Tissue Proteins ; genetics ; Olfaction Disorders ; Receptor, Fibroblast Growth Factor, Type 1 ; genetics ; Sexual Maturation

OBJECTIVETo improve the accuracy of the diagnosis of the disease on the basis of the clinical features and genetic characteristics of patients with Silver Russell syndrome (SRS).

METHODPatients diagnosed with SRS by Price criteria in 2006 to 2011 were reviewed for their clinical manifestations, physical signs, laboratory examinations and treatments.

RESULTTwenty cases with SRS were 0.08-12.17 yr old. Fifteen were male and 5 were female. The clinical characteristics included more than 80% of cases had postnatal growth retardation 100% (20/20), craniofacial dysmorphism 100% (20/20), small for gestation age 95% (19/20), asymmetry and thinning of the face and/or limbs 90% (18/20), fifth finger clinodactyly 80% (16/20), BMI < -2 SDS 80% (16/20). Their height was obviously lagging behind in the bone age. HD SDS/average of bone retardation was 3.08. The two patients with the chief complaint of external genital abnormalities would have aggressive surgical treatment and they did not use the growth hormone (GH) treatment. Only six patients had used the GH treatment. GH treatment at a dose of 0.1 IU/(kg·d) used in 2 cases achieved a growth velocity (GV) 8 - 11 cm/yr but in another 2 cases < 5 cm/yr. In genetic study, 6 patients were found to have 11p15 low methylation, 1 had low and high methylation, 1 had duplication, no relation between clinical and methylation of 11p15 was found.

CONCLUSIONThere were great variations of clinical features in SRS characterized by small for gestation age and/or postnatal growth retardation, craniofacial dysmorphism, asymmetry of the face and/or limbs or ultrafine limbs, fifth finger clinodactyly. Severely low BMI was seen and height was obviously lagging behind in the bone age. The findings of laboratory tests and imaging of SRS were not specific. Some of SRS had 11p15 imprinting defects. The treatment of SRS is mainly symptomatic.

Abnormalities, Multiple ; diagnosis ; genetics ; Adolescent ; Body Height ; Bone Density ; Child ; Child, Preschool ; Chromosomes, Human, Pair 11 ; genetics ; DNA Methylation ; Female ; Genetic Association Studies ; Genomic Imprinting ; Growth Disorders ; diagnosis ; genetics ; Humans ; Infant ; Male ; Retrospective Studies ; Silver-Russell Syndrome ; diagnosis ; genetics

In order to explore the value of reverse transcription(RT)-multiplex nested PCR for detecting PDGFRB gene rearrangement in myeloproliferative disorders (MPD), the PDGFRB rearrangement was detected qualitatively in 146 MPD cases by reverse transcription multiplex nested PCR. The results showed that 8 cases with PDGFRB fusion gene were found in 146 cases, the positive rate was 5.5%. Out of 8 cases with PDGFRB fusion gene, TEL-PDGRB fusion gene was found in 3 cases; HIP1-PDGFRB fusion gene in 2 cases; GIT2-PDGFRB, TP53BP1-PDGFRB and WDP48-PDGFRB fusion gene in 1 case, respectively. It is concluded that RT-multiplex nested PCR is a powerful tool for the detection of PDGFRB rearrangement, which helps to tentatively diagnose MPD and to provide the clues for targeting therapy.
Gene Rearrangement ; Humans ; Multiplex Polymerase Chain Reaction ; Myeloproliferative Disorders ; diagnosis ; genetics ; Receptor, Platelet-Derived Growth Factor beta ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; methods

This study was aimed to explore the applicable value of multiplex nested reverse transcription-polymerase chain reaction (multiplex nested RT-PCR)for the detection of platelet-derived growth factor receptor alpha (PDGFRα) fusion gene in myeloproliferative neoplasms (MPN). Bone marrow or peripheral blood samples from 146 patients with MPN were analyzed by using a novel multiplex nested RT-PCR. The result showed that PDGFRα fusion gene was found in 6 out of the 146 bone marrow or peripheral blood samples, the positive rate was 4.11%, 4 from the 6 patients received treatment with imatinib and showed therapeutic effect. It is concluded that the multiplex nested RT-PCR has a series of advantages such as high sensitivity, specificity, and time-saving, and can be applied for determination of the molecular type of MPN, and also for the diagnosis and therapy of MPN.
Bone Marrow Neoplasms ; diagnosis ; genetics ; Gene Fusion ; Humans ; Multiplex Polymerase Chain Reaction ; Myeloproliferative Disorders ; diagnosis ; genetics ; Receptor, Platelet-Derived Growth Factor alpha ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; methods

OBJECTIVETo conduct genetic testing and prenatal diagnosis for a pregnant women with growth retardation, severe mental retardation, and a history of adverse pregnancies.

METHODSG-banded chromosome analysis, fluorescence in situ hybridization (FISH), and whole genome DNA microarray were used to analyze the patient and her fetus.

RESULTSThe women was found to be a chimera containing two cell lines with 47 and 46 chromosomes, respectively. Both have involved deletion of 18q21.2q23. FISH analysis suggested that the cell line containing 47 chromosomes has harbored a chromosome marker derived from chromosome 15. The marker has contained chromosome 15p involving the SNRPN locus and part of 15q, which gave rise to a karyotype of 47,XX,del18q21.3,+ish mar D15Z1+ SNRPN+[82]/46,XX,del18q21.3[18]. Whole genome DNA microarray confirmed that a 3.044 Mb fragment from 15q11.2q12 was duplicated, which involved NIPA1, SNRPN and other 17 OMIM genes. Duplication of this region has been characterized by low mental retardation, autism, developmental delay. Meanwhile, there was a 17.992 Mb deletion at 18q21.33q23, which contained 39 OMIM genes including TNFRSF11A and PHLPP1. This fragment was characterized by mental retardation, developmental delay, short stature, and cleft palate. Whole genome microarray analysis confirmed that there was a 17.9 Mb deletion at 18q21.33q23, which has been implemented with mental retardation, general growth retardation, short stature, and cleft palate. After genetic counseling, the family decided to terminate the pregnancy at 21st week.

CONCLUSIONCombined chromosome karyotyping, FISH, and whole genome DNA microarray can determine the origin of marker chromosomes and facilitate delineation of its correlation with the clinical phenotype.

Abortion, Eugenic ; Adult ; Chromosome Aberrations ; Chromosome Banding ; Chromosomes, Human, Pair 15 ; genetics ; Chromosomes, Human, Pair 18 ; genetics ; Fatal Outcome ; Female ; Fetus ; abnormalities ; metabolism ; Growth Disorders ; embryology ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Intellectual Disability ; embryology ; genetics ; Karyotype ; Karyotyping ; Prenatal Diagnosis ; methods

Biomarkers ; blood ; Child ; Chorionic Gonadotropin ; blood ; Follicle Stimulating Hormone ; blood ; Growth Disorders ; etiology ; Humans ; Klinefelter Syndrome ; complications ; diagnosis ; genetics ; Magnetic Resonance Imaging ; Male ; Mediastinal Neoplasms ; complications ; diagnosis ; surgery ; Puberty, Precocious ; diagnosis ; etiology ; Teratoma ; complications ; diagnosis ; surgery ; Testis ; pathology