Polymorphisms of MAMLD1 gene in hypospadias

Kalfa, Nicolas; Cassorla, Fernando; Audran, Françoise; Abdennabi, I. Oulad; Philibert, Pascal; Béroud, Christophe; Guys, Jean Michel; Reynaud, Rachel; Alessandrini, P.; Wagner, K. H.; Bréaud, Jean; Valla, Jean Stéphane; Lacombe, G. Morisson; Daurès, Jean‐Pierre; Baskin, Laurence S.; Fukami, Maki; Ogata, Tsutomu; Sultan, Charles

doi:10.1016/j.jpurol.2011.09.005

Cited by 36 publications

(46 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Chen et al (8) showed a weak link between p.N589S and hypospadias. Kalfa showed a higher incidence of p.N589S in a large sample experiment among Caucasians, but this rate was not statistically significant (9). In the present study, statistical analyses on SNP showed that the p.N589S mutation rate was not statistically different from that of hypo spadias among a Chinese population (P>0.05).…”

Section: Discussioncontrasting

confidence: 76%

“…A study recently reported that the MAMLD1 gene mutation was related to the occurrence of hypospadias in a Caucasian population (8,9). To verify its mutation significance in a Chinese population, direct sequencing of polymerase chain reaction (PCR) products was performed in 150 sporadic cases of hypospadias for exploring the diagnostic values of MAMLD1 gene mutation and its relationship with the incidence of hypospadias.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

MAMLD1 Gene Mutation in the Incidence of Hypospadias in the Chinese Population

Zhuang¹,

Bai²,

Zhou³

et al. 2014

Journal of Medical Biochemistry

View full text Add to dashboard Cite

Summary Background: This study aimed to investigate the significance of MAMLD1 mutations in the incidence of hypospa-dias in a Chinese population. Methods: The experimental group consisted of 150 domestic children with hypospadias, aged 0.5 to six years and living in different provinces. A total of 120 normal children, aged two to six years, served as the control group. DNA was extracted for the direct sequencing of MAMLD1 genes. Results: Twelve cases (8.0%) of the missense mutation p.N589S were found in the experimental group, whereas four cases (3.0%) of the same mutation were found in the control group. No significant difference was observed in the mutation rate between the two groups (P>0.05). Four cases (2.7%) had a new missense mutation p.P567S in the experimental group, and three cases (2.5%) possessed the same mutation in the control group. No significant difference was observed between the two groups (P>0.05). Conclusions: In this study, the importance of repeated experiments in mutation-related studies was confirmed, which revealed the difference in predisposing genes among different populations. Although the mutation of the MAMLD1 gene had no apparent connection with the incidence of hypospadias in a Chinese population, a new mutation site of the MAMLD1 gene was discovered, which could provide new research topics for future studies.

show abstract

Section: Discussioncontrasting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

MAMLD1 Gene Mutation in the Incidence of Hypospadias in the Chinese Population

Zhuang¹,

Bai²,

Zhou³

et al. 2014

Journal of Medical Biochemistry

View full text Add to dashboard Cite

show abstract

“…In particular, recent observations by Coutant et al (37), as well as our own experience (38), suggest that an SF1 gene mutation may be associated in newborn/infant males with PAIS-like phenotype. In addition, we recently identified two mutations of MAMLD1 responsible for severe hypospadias and micropenis in male children with PAIS-like phenotype (39). Accordingly, we investigated the 28 patients with PAIS-like phenotype for SF1 and MAMLD1 gene mutations, but none was identified.…”

Section: Discussionmentioning

confidence: 99%

‘Idiopathic’ partial androgen insensitivity syndrome in 28 newborn and infant males: impact of prenatal exposure to environmental endocrine disruptor chemicals?

Gaspari

Paris

Philibert

et al. 2011

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: 46,XY disorders of sex differentiation (46,XY DSD) can be due to a testis determination defect, an androgen biosynthesis defect, or androgen resistance (complete or partial androgen insensitivity syndrome (PAIS), or 5a reductase deficiency). We aimed to evaluate the impact of a prenatal contamination by environmental xenoestrogens in 'idiopathic' PAIS-like phenotype. Subjects: We investigated 28 newborn/infant males with 46,XY DSD, normal androgen production, and no androgen receptor or steroid-5aR type II enzyme (SRD5A2) gene mutations. Methods: To exclude other genetic defects, we sequenced the steroidogenic factor 1 (SF1) and mastermind-like domain-containing 1 (MAMLD1) genes, which were recently found to be associated with the PAIS-like phenotype. Parents were interviewed about their environmental/occupational exposure to endocrine disrupting chemicals (EDCs) before/during the patients' fetal life. Total estrogenic bioactivity of patient serum was analyzed by ultrasensitive bioassay. Results: All the patients had normal SF1 sequence and one patient showed a double polymorphism of MAMLD1. Eleven (39.3%) of the 28 patients had reported parental fetal exposure to EDCs. The mean estrogenic bioactivity in these 11 patients with fetal EDC exposure (6.65G8.07 pg/ml) versus 17 cases without contamination (1.27G0.34 pg/ml) and controls (1.06G0.44 pg/ml; P!0.05) was elevated. Conclusions: Our results indicate that the 'idiopathic' PAIS-like phenotype may in some cases be related to EDC contamination during fetal life.

show abstract

“…To date, no correlation has been found between the severity of the phenotype and complete or partial loss of transactivation activity ( table 2 ; fig. 4 ) [Fukami et al, 2006;Kalfa et al, 2008Kalfa et al, , 2011.…”

Section: Discussionmentioning

confidence: 99%

“…Since this first description, MAMLD1 mutations have been described in several patients with hypospadias [Fukami et al, 2006;Kalfa et al, 2008Kalfa et al, , 2012Chen et al, 2010]. Moreover, the S-S haplotype, which entails the presence of a double MAMLD1 gene polymorphism (p.P359S and p.N662S), has been found to be more frequent in patients with hypospadias than in controls [Chen et al, 2010;Kalfa et al, 2011;van der Zanden et al, 2012].…”

mentioning

confidence: 99%

A Novel Hemizygous Mutation of <b><i>MAMLD1</i></b> in a Patient with 46,XY Complete Gonadal Dysgenesis

Ruiz-Arana¹,

Hübner²,

Cetingdag³

et al. 2015

Sex Dev

View full text Add to dashboard Cite

MAMLD1 is suggested to play a role in the development of 46,XY disorders of sexual development (46,XY DSD). So far, mutations in this gene have been detected in several cases of hypospadias with normal testosterone levels at birth. From in vitro studies it was concluded that Mamld1 might transiently affect testosterone synthesis during genital development. We describe the first MAMLD1 mutation in a 46,XY patient with complete gonadal dysgenesis. The novel MAMLD1 missense mutation (p.P677L) results in a severely reduced transactivation in vitro of the promoter of the MAMLD1 target gene HES3/Hes3. However, as knowledge about the functional role of MAMLD1 in gonadal development is limited, we suggest that additional factors (digenic or oligogenic cause) play a role in the development of complete gonadal dysgenesis in this patient.

show abstract

Polymorphisms of MAMLD1 gene in hypospadias

Cited by 36 publications

References 31 publications

MAMLD1 Gene Mutation in the Incidence of Hypospadias in the Chinese Population

MAMLD1 Gene Mutation in the Incidence of Hypospadias in the Chinese Population

‘Idiopathic’ partial androgen insensitivity syndrome in 28 newborn and infant males: impact of prenatal exposure to environmental endocrine disruptor chemicals?

A Novel Hemizygous Mutation of <b><i>MAMLD1</i></b> in a Patient with 46,XY Complete Gonadal Dysgenesis

Contact Info

Product

Resources

About