Correlation between deletion patterns of SMN and NAIP genes and the clinical features of spinal muscular atrophy in Japanese patients

We conducted molecular analysis of two candidate genes for spinal muscular atrophy (SMA), the survival motor neuron gene (SMN) and the neuronal apoptosis inhibitory protein gene (NAIP), in 16 Japanese patients with SMA and compared the phenotypic features of SMA in these patients with the corresponding genotypes. Exons 7 and/or 8 of SMN were homozygously deleted in 11 SMA type I (Werdnig-Hoffmann disease) patients, two SMA type II patients and one SMA type III patient. Exons 5 and 6 of NAIP were homozygously deleted in six SMA type I patients. No patient had a deletion in NAIP without a deletion in SMN. Mechanical ventilation was required during the first 7 months of life in the SMA type I patients who had a deletion in both SMN and NAIP. Ventilatory support was initiated within 2 years after birth in patients who had a deletion in SMN but not in NAIP. We detected homozygous deletion of exon 5 of NAIP in the unaffected mothers of two SMA type I patients. In these families, the patients exhibited a deletion in both SMN and NAIP. The parents and unaffected siblings of these patients did not have a deletion in SMN. The present findings support the hypothesis that SMN deletion plays an important role in the development of SMA and suggest that combined deletion of both SMN and NAIP may be relevant for determining the disease severity.     

Nosocomial infection in small for gestational age newborns with birth weight <1500 g: a multicentre analysis

Objective

To investigate whether preterm newborns who are small for gestational age are at increased risk of nosocomial infections and necrotising enterocolitis.

Design, setting and subjects

The German national surveillance system for nosocomial infection in very low birthweight infants uses the US Centers for Disease Control and Prevention criteria. 2918 newborns (24–28 weeks), born between 2000 and 2004, were selected after application of predefined inclusion criteria to ensure similar proportions of small and appropriate weight for gestational age newborns across gestational age groups.

Main outcome measures

The outcome criterion was at least one episode of nosocomial sepsis, pneumonia or necrotising enterocolitis. Adjusted odds ratios and corresponding 95% CIs were calculated based on general estimating equation models.

Results

The study population consisted of 13% (n = 392) small and 87% (n = 2526) appropriate weight for gestational age infants. 33% (n = 950) of the infants experienced at least one episode of sepsis: 42% (n = 163) of small and 31% (n = 787) of appropriate weight for gestational age newborns (adjusted OR 1.41, 95% CI 1.05 to 1.89). Pneumonia was diagnosed in 6% (n = 171) of infants: 8.4% (n = 33) of small and 5.5% (n = 138) of appropriate weight for gestational age newborns (adjusted OR 1.57, 95% CI 1.19 to 5.57). Necrotising enterocolitis was documented in 5.2% (n = 152) of infants: 7.1% (n = 28) of small and 4.9% of (n = 124) appropriate weight for gestational age newborns (adjusted OR 1.20, 95% confidence interval 0.75 to 1.94).

Conclusions

Growth‐retarded preterm infants seem to be at increased risk of nosocomial infection, irrespective of the responsible pathogen. Future immunological research should elucidate potential causal associations.Very low birthweight (VLBW, <1500 g) newborns are at increased risk of morbidity and mortality. Besides their immaturity, risk profiles can vary due to a multitude of factors. Growth retardation is one factor conferring additional risk. Recent studies have consistently shown an increased mortality risk for small for gestational age (SGA) infants,1,2,3 but results regarding morbidity are conflicting.4,5,6Nosocomial infection has a large impact on neonatal survival and has important cost implications,7,8 affecting up to 40% of babies in neonatal intensive care units (NICUs).9,10,11,12,13 Immunological immaturity (eg, poor phagocytosis or hypogammaglobinaemia), exposure to invasive procedures and prolonged hospitalisation predispose VLBW newborns to nosocomial infection.7,14,15 However, little is known about nosocomial infection in SGA newborns.4,11,16,17,18,19We addressed this issue in a large, multicentre analysis to investigate the association of being SGA and being at increased risk of nosocomial infection—that is, sepsis and pneumonia. In addition, necrotising enterocolitis (NEC) was considered as an outcome criterion.     

Association d''une dysgénésie gonadique mixte et d''une forme non classique de bloc de la 21-hydroxylase

Background.

The rare association of mixed gonadal dysgenesis and non classical congenital hyperplasia by 21-hydroxylase deficiency poses the problem of their respective responsability in the development of sexual ambiguity.

Case report.

In a newborn with ambiguous genitalia, blood 17-OH progesterone was moderately elevated (3.9 to 14.1 ng/mL) leading to the diagnosis of non-classical 21 hydroxylase deficiency. Molecular studies later confirmed this diagnosis. However, the presence of a palpable gonad and the caryotype (45 X/46 XY mosaicism) indicated a mixed gonadal dysgenesis as the cause of sexual ambiguity. Histological examination revealed the presence of a testis and a streak gonad.

Conclusion.

This observation emphasizes the need for a complete clinical and biological analysis in all newborns with sexual ambiguity.     

Effects of <Emphasis Type="Italic">Bifidobacterium</Emphasis> supplementation on intestinal microbiota composition and the immune response in healthy infants

Background

Intestinal microbiotas are thought to be the most important source of maturational stimuli to the development of the immune system. However, few studies have focused on the development of T helper (Th) 1 immune response and antibody response to vaccinations in healthy infants, especially in a large cohort. Through this randomized, double-blind control trial, we investigated the effects of Bifidobacterium longum BB536 (BB536) supplementation on intestinal microbiota composition and the immune response in term infants.

Methods

In total, 300 healthy newborns were recruited, randomized and fed formula either supplemented with BB536 or with no supplementation. Stool samples were analyzed at months 2, 4 and 11. The representative cytokine for Th1 [interferon-γ (IFN-γ)] and Th2 [interleukin-4 (IL-4)] secretion cells were measured using enzyme-linked immunospot assay at 4 and 7 months of age. The antibody response to vaccines was measured at months 7 and 11.

Results

A total of 264 infants completed the study. The amount of bifidobacteria and the bifidobacteria/ Enterobacteriaceae ratio (B/E) were significantly higher in the BB536 supplementation group at months 2 and 4. The number of IFN-γ secretion cells and the ratio of IFN-γ/IL-4 secretion cells were increased in the BB536 supplementation group at 7 months. Moreover, the higher value of B/E in the early stages seems to be related to the increased Th1 response. No difference was observed between groups in the antibody response after vaccination.

Conclusion

BB536 has positive effects on establishing a healthy intestinal microbiota early in life, and it also plays an important role in improving the Th1 immune response.

     

Near-miss apparent SIDS from adrenal crisis

Objective

Adrenal crisis from salt-losing congenital adrenal hyperplasia (CAH) typically occurs in the first 2 weeks of life. We evaluated 3 infants with adrenal crisis who presented at 6 to 8 months of age with near-miss sudden infant death syndrome (SIDS).

Subjects

Three 46,XY phenotypic female infants presented near death at 6 to 8 months of age with adrenal crisis and unmeasurable steroid hormones consistent with congenital lipoid adrenal hyperplasia (lipoid CAH).

Methods

We sequenced genes potentially causing this phenotype: steroidogenic acute regulatory protein (StAR), the cholesterol side-chain cleavage enzyme, adrenodoxin reductase, adrenodoxin, and steroidogenic factor 1 (SF1). Site-directed mutagenesis and functional assays were performed for the missense mutation.

Results

Hormonal values showed complete absence of adrenal and gonadal steroids. Patient 1 was a compound heterozygote for missense mutation R140P and an mRNA splice donor site mutation in the StAR gene. The R140P mutation was wholly inactive in vitro. Patient 2 was homozygous for a 7 base pair StAR deletion causing a frameshift. No mutations were found in Patient 3, suggesting a novel disease.

Conclusions

Although genetic disorders of steroidogenesis typically present in the first month of life, some defects, especially those in StAR, can present in mid-infancy, when adrenal hyperplasias are rarely considered. Adrenal insufficiency is a subtle disorder that may cause cardiovascular collapse, causing unexplained infant death that resembles SIDS.     

New Single Nucleotide Deletion In the SMPD1 Gene Causes Niemann Pick Disease Type A in a Child from Southwest Iran: A Case Report

Objective

Niemann Pick disease (NPD) type A (NPA: MIM #257200) is a lipid storage disorder with an autosomal recessive inheritance and occurrs by defect of the SMPD1 gene encoding sphingomyelinase. Disruption of this enzyme leads to the accumulation of sphingomyelin in brain and liver, which in turn causes dysfunction or damage of tissue.

Methods

We report firstly a 2.5 year old boy with NPA in southwest Iran. Initially, the diagnosis was resulted on the basis of clinical symptoms. The genomic DNA of the suspected individual was subjected to exon sequencing of the SMPD1 gene. According to the human reference sequence {"type":"entrez-nucleotide","attrs":{"text":"NM_000543.4","term_id":"300795568","term_text":"NM_000543.4"}}NM_000543.4, a novel single guanine deletion resulting in a frameshift mutation (p.Gly247Alafs*9) was observed in the SMPD1 gene that might be causative for the outcome of the disease.

Findings

The present report is the first molecular genetics diagnosis of the NPA in southwest Iran. The detected deletion in the SMPD1 gene is remarkable because of its novelty.

Conclusion

Despite similar morbidity SGA infants exhibited higher lethal complication rates following delayed meconium passage compared to AGA infants.     

Clinical and molecular characterization of children with neonatal diabetes mellitus at a tertiary care center in northern India

Objective

To study the genetic mutations and clinical profile in children with neonatal diabetes mellitus

Methods

Genetic evaluation, clinical management and follow-up of infants with neonatal diabetes

Results

Eleven infants were studied of which eight had permanent neonatal diabetes. Median age at presentation was 8 weeks and mean (SD) birth weight was 2.4 (0.5) kg. Pathogenic genetic mutations were identified in 7 (63.6%) children; 3 infants with mutations in KCNJ11 gene and 1 in ABCC8 were switched to oral sulfonylureas; 2 infants had mutations in INS and 1 in ZFP57.

Conclusion

Neonatal diabetes mellitus is a heterogeneous disorder. Identification of genetic cause guides clinical management.

     

Syndrome de Jacobsen, thrombopénie et déficit immunitaire humoral

Background

Clinical features of Jacobsen syndrome include facial dysmorphism, congenital heart defects, digit anomalies and mild to moderate psychomotor retardation. Thrombocytopenia or pancytopenia is observed in one half of patients.

Patients

Two unrelated children, a 6-month- and a 12-year-old, presented with a moderate thrombocytopenia associated with the clinical features of Jacobsen syndrome. Bone marrow aspirates showed, in both patients, normal cellularity with an increased number of micromegacaryocytes. Chromosome analysis showed a partial deletion of the long arm of chromosome 11. The 12-year-old patient had a history of upper respiratory airways infections with immune humoral deficiency (decreased level of IgA and IgM) which, to our knowledge, has never been reported.

Conclusion

Jacobsen syndrome is a cause of inherited thrombocytopenia in children. Humoral immune functions must be explored in patients with a history of repeated infections.     

Clinical Characteristics and Associated Congenital Lesions with Tracheomalacia in Infants

Objective

To describe clinical presentation, bronchoscopy findings and associated anomalies in cases of congenital tracheomalacia in infants (age <1y).

Methods

Hospital record review of 88 infants (mean age 8 mo, 57 males) diagnosed as having tracheomalacia by flexible bronchoscopy between 2012 and 2015.

Results

The predominant features were wheeze (57.9%), stridor (42.1%), cough (38.6%), pneumonia (29.5%) and collapse (12.5%). On bronchoscopy, malacia was observed in lower half of trachea in 51 (57.9%) infants. Synchronized airway lesions observed were laryngomalacia (30.7%) and bronchomalacia (3.4%). 15 (17%) infants had associated congenital heart disease and 21 (23.8%) required care in intensive care unit.

Conclusion

Wheeze,stridor and cough are the main symptoms in tracheomalacia. Laryngomalacia and congenital heart diseases are the most common other anomalies associated in these infants.

     

Thyroid status of iodine deficient newborn infants living in central region of Turkey: a pilot study

Background

Iodine deficiency (ID) during the fetal and neonatal periods can lead to neonatal hypothyroidism. This study was conducted to evaluate the effect of ID on the thyroid hormone level of newborns living in Turkey.

Methods

Between 1998 and 2013, 71 newborns with a urinary iodine concentration <100 μg/L were recruited into the study. Data on thyroid volume, free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroglobulin (Tg) were collected from all newborns, and on breast milk iodine from their mothers. Infants who were classified as having congenital hypothyroidism (TSH >40 mU/L and fT4 <8.5 pmol/L) were treated with levothyroxine (n=26, T group), while the remaining infants remained untreated (n=45, UT group). Thyroid hormones were subsequently measured 7-14 days later in a sub-sample of both treated and untreated infants.

Results

The average values at the time of admission were as follows [median (min-max)]. fT3: 5.0 (2.8-7.1) pmol/L, fT4: 7.7 (0.13-19.1) pmol/L, TSH: 75 (14-426) mU/L, Tg: 464 (226-1100) ng/mL, urinary iodine concentration (UIC): 30 (0-61) μg/L, breast milk iodine levels: 21 (10-150) μg/L, thyroid ultrasound (USG): 1.10 (0.24-1.95) mL for the T group; and fT3: 5.7 (1.7-12.7) pmol/L, fT4: 16.2 (9.9-33.5) pmol/L, TSH: 5.4 (0.63-41.8) mU/L, Tg: 171 (15-2124) ng/mL, UIC: 39 (0-90) μg/L, breast milk iodine levels: 47 (10-120) μg/L, thyroid USG: 0.75 (0.35-1.72) mL for the UT group. A significant difference was found between groups in respect to fT3, fT4, TSH and Tg levels. No significant difference in thyroid ultrasonography, UIC, and breast milk iodine levels was found between the two groups. The Tg levels of 50 out of 71 patients were measured, 40 (80%) of whom had Tg levels above the normal range (101 ng/mL).

Conclusions

In our country, despite the use of iodized salt, congenital hypothyroidism due to ID remains a problem. The Tg level of newborns can be used as a good indicator of ID.

     

Improvement of survival in infants with congenital diaphragmatic hernia in recent years: effect of ECMO availability and associated factors

Background/Purpose

Survival of patients with congenital diaphragmatic hernia (CDH) depends both on non-modifiable congenital conditions and on modifiable pre and postnatal management. ECMO improves survival up to 80% in neonates with CDH in the best ECMO centers worldwide. The first Neonatal ECMO Program in Chile was started in our University in 2003. Our objective is to determine the impact of a Neonatal ECMO Program in a level III NICU on newborns with CDH.

Methods

Data of all newborns with CDH admitted to our NICU was separated into two groups: pre ECMO (1996–2003) and ECMO (2003–2007). Crude and adjusted odds ratios for 24 months survival were estimated by logistic regression.

Results

Data of 46 newborns with CDH was analysed, 20 in the pre ECMO and 26 in the ECMO period. Patient characteristics were similar in both groups; however, 24-month survival increased significantly from 25% (5/20) in the pre ECMO period to 77% (20/26) in the ECMO period (P = 0.001). Adjusted odds ratios for 24-month survival were 26.98 for OI ≤ 40, 7.58 for 5 min Apgar ≥ 7 and 17.5 for ECMO availability.

Conclusions

The establishment of an ECMO program was associated with a significant increase in long-term survival for infants with CDH.     

Évaluation de la glycémie des nouveau-nés de petits poids avant la 24 heure de vie au CHU-Tokoin de Lomé

Objective

To assess the glycemia of low-weight newborns (LWNBs) during their first 24 h of life as well as their mother's glycemia.

Patients and method

This was a cross-sectional prospective study within a case-control group, conducted at Lomé University Hospital (nationwide main hospital) from January to May 2006. One hundred thirty-nine LWNBs and 150 eutrophic term newborns (ETNBs), 98 mothers of LWNBs (MLWNBs), and 145 mothers of ETNBs (METNBs) were screened and monitored on glycemia dosage.

Results

The average glycemia level of the LWNBs (0.34 ± 0.27 g/l) was significantly greater than the ETNBs’ glycemia level (0.30 ± 0.14 g/l); it was nearly the same for the mean glycemia level of the MLWNBs (0.82 ± 0.2 g/l) and the METNBs (0.77 ± 0.1 g/l). Neonatal hypoglycemia during the first 24 h of life was less frequent (RR = 0.8) in the LWNBs (61.15%) than in the ETNBs (80%). The positive correlation between gestational age and glycemia was higher in the ETNBs (r = 0.17) than in the LWNBs (r = 0.07). This positive correlation between birthweight and glycemia was lower in the LWNBs (r = 0.17) compared to the ETNBs (r = 0.37); this was not the case within the group of the ETNBs (r = 0.02) compared to the group of the LWNBs (r = 0.34) concerning the correlation between the glycemia of mothers and newborns.

Conclusion

The early hypoglycemia was much greater in the ETNBs compared to the LWNBs. Therefore, it is necessary to systematically start breastfeeding all newborns within their first hours of life whatever their gestational age, in order to solve these metabolic disorders.     

Cerebral ultrasound findings in infants exposed to crack cocaine during gestation

Background

Prenatal exposure to cocaine has been associated with a wide spectrum of structural abnormalities in infant brains. The growing use of crack, a smokable and extremely addictive form of cocaine, could exacerbate the situation.

Objective

The purpose of this study was to determine the frequency, type and severity of cerebral lesions detected by transfontanellar US in newborns exposed to crack during gestation.

Materials and methods

This was a retrospective study, involving a review of the medical records of children who were born to crack-using women and who were subjected to transfontanellar US imaging during their first days of life.

Results

Transfontanellar US revealed abnormalities in 45/129 newborns examined (34.9%). The changes detected were subependymal cysts in 24 infants (18.6%), lenticulostriate vasculopathy in 18 infants (14%), subependymal hemorrhage in 9 infants (7%), and choroid plexus cysts in 9 infants (7%).

Conclusion

All of the abnormalities found by US examination were discrete and likely without clinical significance for the babies. However, prospective studies with a long period of tracking are needed to determine whether there are later consequences on the neurodevelopment of children with prenatal exposure to crack.     

Parotidite bactérienne aiguë chez les nourrissons de moins de 3 mois : étude rétrospective dans un centre hospitalier universitaire

Background

Acute bacterial parotitis is a rare infectious disease in infants under 3 months of age.

Objectives

To describe the clinical characteristics and the course of acute bacterial parotitis in infants less than 3 months old.

Patients and methods

Infants under 3 months of age, hospitalized at Robert Debré university hospital, Paris, France, between January 2005 and December 2009 for acute bacterial parotitis, were included in a retrospective study.

Results

Five infants less than 3 months of age were included in this study, for a frequency of 2.5/1000 hospitalizations in this age group. All were born at term, 4 of 5 were male. Three of the 5 patients had specific clinical signs of parotitis on admission. One patient had septic shock on admission. The ultrasound confirmed the parotitis in all cases. No parotid abscess was demonstrated on imaging. All patients had at least one abnormal inflammatory biological test (WBC, CRP, PCT). Bacteria were identified in 4 of 5 cases: Staphylococcus aureus was isolated in the pus culture of the Stenon duct in 2 patients and a group B Streptococcus was isolated from blood culture of 2 other patients. The duration of intravenous antibiotic therapy varied from 4 to 13 days, and the total duration of antibiotic therapy was between 10 and 16 days. No surgical procedures were needed.

Conclusion

Acute bacterial parotitis in infants under 3 months of age might be associated with localized infections due to S. aureus, but also with a more severe clinical presentation due to group B streptococcus infection. Early diagnosis and appropriate antibiotic therapy might prevent the progression to serious complications.     

Croissance fœtale du prématuré de Haute-Normandie

Background.

Fetal growth standards of preterm infants are different from one study to another, especially for extremely preterm babies.

Population and methods.

Between 1976 and 1990, a cross-sectional study of the resulting intrauterine growth of premature newborns from Haute-Normandie (France) was conducted by collecting data of the compulsory health certificate set up in the first week after birth. In spite of exclusions, curves for obstetrical terms ranging from 28 to 36 weeks of gestational age were settled. Equivalents of 8,042 birth weights, 7,792 statures, 8,041 head circumferences and 6,737 ponderal index were used.

Results.

Comparing our results with those published in the literature, we observed short differences for mean or middle values: from less than 170 to more than 180 g for weight, from less than 1 to more than 2.6 cm for stature and from less than 1 to more than 1.9 cm for head circumference.

Conclusion.

The selected normal lower threshold for each parameter and the varieties of fetal growth inadequacy are under discussion.     

Maturation of gastric electrical activity, gastric emptying and intestinal permeability in preterm newborns during the first month of life

Objectives

Respiratory Syncytial Virus (RSV) is the leading cause of hospitalization for lower respiratory tract infections (LRTI) in young children worldwide. We evaluate the epidemiological and clinical patterns of RSV infection in infants hospitalized for LRTI in in Palermo, South Italy, Sicily.

Methods

We collected the demographic details of infants hospitalized to G. Di Cristina Children's Hospital in Palermo for LRTI between November 2005 and May 2006. We also included all cases occurred in newborns hospitalized in the Neonatal Intensive Care Unit (NICU) Of Palermo.

Results

During the studied period, 335/705 hospitalized infants for LRTI were enrolled in the study. The trend of hospitalization started in late winter and lasting until May 2006 with an epidemic peak in spring. 178/335 infants tested for viral infection showed RSV disease. Three cases occurred in preterm newborns hospitalized from birth in NICU. The likelihood to be RSV+, rather than RSV negative (RSV-) was higher for infants < 6 months and lower for infants with history of breast feeding (P < 0.05). RSV infection was associated with a higher likelihood to be admitted to intensive care unit and to a longer hospitalization and oxygen therapy.

Conclusion

The study shows that, in Sicily, RSV is an important cause of LRTI in infants. The seasonal distribution shows that both LRTI and RSV infections peak in late spring, in contrast to Northern Italy. Our data could help to define the regional appropriate start of prophylactic interventions.     

Nasal high flow therapy in very low birth weight infants with mild respiratory distress syndrome: a single center experience

Background

Pulmonary disorders and respiratory failure represent one of the most common morbidities of preterm newborns admitted to neonatal intensive care units (NICUs). The use of nasal high-flow therapy (nHFT) has been more recently introduced into the NICUs as a non-invasive respiratory (NIV) support.

Methods

We performed a retrospective study to evaluate safety and effectiveness of nHFT as primary support for infants born <?29 weeks of gestation and/or VLBW presenting with mild Respiratory Distress Syndrome (RDS).The main outcome was the percentage of patients that did not need mechanical ventilation. Secondary outcomes were rate of bronchopulmonary dysplasia (BDP), air leaks, nasal injury, late onset sepsis (LOS), intraventricular hemorrhage (IVH), retinopathy (ROP), necrotizing enterocolitis (NEC), hemodynamically-significant patent ductus arteriosus (PDA) and death.

Results

Sixty-four preterm newborns were enrolled. Overall, 93% of enrolled patients did not need mechanical ventilation. In a subgroup analysis, 88.5% of infants <?29 weeks and 86.7% of infants ELBW (<?1000 g BW) did not need mechanical ventilation.BPD was diagnosed in 26.6% of preterms enrolled (Mild 20%, Moderate 4.5%, Severe 1.5%). In subgroup analysis, BPD was diagnosed in 53.9% of newborns with GA <?29 weeks, in 53.3% of ELBW newborns and in 11.1% of small for gestational age (SGA) newborns.Neither air leaks nor nasal injury were recorded as well as no exitus occurred. LOS, IVH, ROP, NEC and PDA occurred respectively in 16.1%, 0%, 7.8%, and 1.6% of newborns.

Conclusions

According to our results, n-HFT seems to be effective as first respiratory support in preterm newborns with mild RDS. Further studies in a larger number of preterm newborns are required to confirm nHFT effectiveness in the acute phase of RDS.

     

Hotspots in <Emphasis Type="Italic">PTPN11</Emphasis> gene among Indian children with Noonan syndrome

Objectives

To test for PTPN11 mutations in clinically diagnosed cases of Noonan syndrome.

Methods

17 individuals with clinical diagnosis of Noonan syndrome were included in the study. Sanger sequencing of all the 15 exons of PTPN11 was done. A genotype-phenotype correlation was attempted.

Results

Mutation in PTPN11 was detected in 11 out of 17 (64.7 %) patients with Noonan syndrome; 72% had mutation in exon 3 and 27 % had mutation in exon 13.

Conclusion

PTPN11 mutation accounts for 64.7% of cases with clinical features of Noonan syndrome in India. Majority of the mutations are in exon 3 and exon 13 of PTPN11, making them the hotspots in Indian population.

     

Polymorphism of 3′ UTR of MAMLD1 gene is also associated with increased risk of isolated hypospadias in Indian children: a preliminary report

Objective

To study MAMLD1 gene polymorphisms, serum LH and testosterone levels amongst Indian children with isolated hypospadias (IH) and controls.

Materials and methods

Screening of the MAMLD1 gene was performed by PCR sequencing method in 100 Indian children aged 0–12 years presenting with IH and 100 controls. LH and testosterone hormone levels were also assessed (categorized in four age-wise groups).

Results

IH subjects had significantly higher incidence of MAMLD1 polymorphism as compared to controls (33 vs 15 %, p = 0.01). Of various genomic variants identified in this study, the noteworthy novel ones were missense mutation P299A and single nucleotide polymorphism c.2960C>T in 3′ UTR of Exon 7. While p 299A was found to cause protein structural instability consequent to amino acid change, eighty percent subjects with c.2960C>T in 3′ UTR of Exon 7 (corresponding to newly discovered currently non-validated exon 11) were found to have lower testosterone levels when compared with their age group mean. IH showed statistically higher incidence of c.2960C>T in comparison to controls (22 vs 10 %, p value 0.046) and about 2.5-folds higher risk of this anomaly.

Conclusion

Occurrence of MAMDL1 gene polymorphisms, specially of c.2960C>T in 3′ UTR of its exon 7 is associated with a higher risk of IH in Indian children, probably by lowering androgenic levels.