POU class 1 homeobox 1 gene polymorphisms associated with growth traits in Korean native chicken.

OBJECTIVE: POU class 1 homeobox 1 (POU1F1) mediates growth hormone expression and activity by altering transcription, eventually resulting in growth rate variations. Therefore, we aimed to identify chicken POU1F1 polymorphisms and evaluate the association between single nucleotide polymorphisms (SNPs) and growth-related traits, and logistic growth curve parameter traits (α, ß, and γ). METHODS: Three SNPs (M_1 to M_3) were used to genotype 585 F1 and 88 F0 birds from five Korean native chicken lines using a polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: Single marker analyses and traits association analyses showed that M_2 was significantly associated with body weight at two weeks, weight gain from hatch to 2 weeks, and weight gain from 16 to 18 weeks (p<0.05). M_3 was significantly associated with weight gain from 14 to 16 weeks and from 16 to 18 weeks, and asymptotic body weight (α) (p<0.05). No traits were associated with M_1. The POU1F1 haplogroups were significantly associated with weight gain from 14 to 16 weeks (p = 0.020). Linkage disequilibrium test and Haploview analysis shown one main haploblock between M_2 and M_3 SNP. CONCLUSION: Thus, POU1F1 significantly affects the growth of Korean native chickens and their growth curve traits.

A Novel Splice-Site Deletion in the POU1F1 Gene Causes Combined Pituitary Hormone Deficiency in Multiple Sudanese Pedigrees.

Pathogenic variants within the gene encoding the pituitary-specific transcription factor, POU class 1 homeobox 1 (POU1F1), are associated with combined pituitary hormone deficiency (CPHD), including growth hormone, prolactin, and thyrotropin stimulating hormone deficiencies. The aim of the study was to identify genetic aetiology in 10 subjects with CPHD from four consanguineous Sudanese families. Medical history, as well as hormonal and radiological information, was obtained from participants' medical records. Targeted genetic analysis of the POU1F1 gene was performed in two pedigrees with a typical combination of pituitary deficiencies, using Sanger sequencing, and whole-exome sequencing was performed in the other two pedigrees, where hypocortisolism and additional neurologic phenotypes were also initially diagnosed. In POU1F1 gene (NM_001122757.2) a novel homozygous splice-site deletion-namely, c.744-5_749del-was identified in all 10 tested affected family members as a cause of CPHD. Apart from typical pituitary hormonal deficiencies, most patients had delayed but spontaneous puberty; however, one female had precocious puberty. Severe post-meningitis neurologic impairment was observed in three patients, of whom two siblings had Dyke-Davidoff-Masson syndrome, and an additional distantly related patient suffered from cerebral infarction. Our report adds to the previously reported POU1F1 gene variants causing CPHD and emphasises the importance of genetic testing in countries with high rates of consanguineous marriage such as Sudan. Genetic diagnostics elucidated that the aetiologies of hypopituitarism and brain abnormalities, identified in a subset of affected members, were separate. Additionally, as central hypocortisolism is not characteristic of POU1F1 deficiency, hydrocortisone replacement therapy could be discontinued. Elucidation of a genetic cause, therefore, contributed to the more rational clinical management of hypopituitarism in affected family members.

Extreme Short Stature and Severe Neurological Impairment in a 17-Year-Old Male With Untreated Combined Pituitary Hormone Deficiency Due to POU1F1 Mutation.

Background: POU1F1 is an essential transcription factor for the differentiation, proliferation and survival of somatotrophs, lactotrophs, and thyrotrophs. Mutations in the POU1F1 gene are characterized by growth hormone (GH), thyrotropin, and prolactin deficiencies, commonly presenting with growth retardation and central hypothyroidism. Since the first report in 1992, more than 25 mutations have been identified in POU1F1. Case Description: We describe a 17-year-old male who presented to our Pediatric Endocrinology clinic with extreme short stature (height 81.7 cm, -9.3 SD), cognitive impairment, deaf-mutism, and neurological disabilities. L-thyroxine supplemental therapy, which had been initiated at the age of 6 months but ceased due to non-compliance, was reintroduced at presentation. GH therapy was initiated at 19 years of age, resulting in 42 cm linear growth, to a final height of 124 cm. Sequencing of POU1F1 revealed a previously described homozygous insertion mutation-c.580_581insT, p (Thr194Ilefs*7)-in exon 4 causing a frameshift that introduces a stop codon 7 amino acids downstream, leading to a severely truncated protein lacking the homeodomain. Conclusion: This case report sheds light on the natural history of untreated patients with POU1F1 mutations and raises awareness for early diagnosis and adequate treatment of central congenital hypothyroidism and GH deficiency.

Precocious or early puberty in patients with combined pituitary hormone deficiency due to POU1F1 gene mutation: case report and review of possible mechanisms.

Central precocious puberty (CPP) or early puberty (EP) is a rare entity in combined pituitary hormone deficiency (CPHD), the latter caused by mutations in pituitary transcription factor genes. The early onset of puberty in two patients with CPHD with POU1F1 gene mutation was evaluated. A 3-month-old boy was diagnosed with central hypothyroidism, and L-thyroxine was commenced. He was referred for the evaluation of short stature at 20 months of age. Anthropometric evaluation revealed severe short stature (- 6.1 SDS), and growth hormone (GH) and prolactin deficiencies were diagnosed. Homozygous POU1F1 gene mutation (c.731T>G, p. I244S) was also detected. Testicular enlargement and high luteinizing hormone (LH) levels were observed at 7 years and 9 months of age while he was on GH and L-thyroxine treatment. Due to rapid progression of puberty, gonadotropin-releasing hormone analogue (GnRHa) was initiated at 11.3 years of age. This patient recently turned 19.2 years old, and his final height was - 2.3 SDS. The second patient, a 6-month-old boy, was also referred for growth retardation. His height was - 2.7 SDS, and GH and thyroid-stimulating hormone (TSH) deficiencies were diagnosed. He also had homozygous (c.10C>T, p.Q4*) POU1F1 gene mutation. Onset of puberty was relatively early, at 10 years, with advanced bone age. He was on GnRHa treatment between 11.5 and 12.5 years of age. Recent evaluation of the patient was at 13.6 years of age, and he is still on levothyroxine and GH treatment. The relationship between the POU1F1 genotype and CPP or EP has not as yet been firmly established in humans. Animal studies have revealed that the Pou1f1 gene has a major effect on regulation of GnRH receptor function and the Gata2 gene. It has also been demonstrated that this gene controls gonadotrope evolution and prevents excess gonadotropin levels. Further studies are, however, needed to elucidate the relation between POU1F1 function and CPP.

Polymorphism of sheep POU1F1 gene exon 6 and 3'UTR region and their association with milk production traits.

The purpose of the study was to detect the AluI and DdeI polymorphisms within POU1F1 gene exon 6 and 3'UTR region in Turkish sheep breeds, and their association with milk productive traits. Jugular blood samples were collected from 50 Sakiz, 50 White Karaman, and 50 Awassi sheep using EDTA as an anticoagulant. PCR-RFLP and sequencing analysis were performed to investigate possible polymorphisms in the exon 6 and 3' flanking region of the sheep POU1F1 gene. The PCR products were digested with restriction endonuclease AluI and DdeI, and biallelic polymorphism was found with restriction endonuclease AluI and two genotypes (TT (296 bp and 173 bp) and CC (235 bp, 173 bp and 61 bp)) were detected. White Karaman and Awassi breeds did not show polymorphisms for AluI restriction sites. No polymorphism at the DdeI cleavage sites was detected in the three sheep breeds. Significant statistical results were found in milk yield ((***)P0.001), fat ((***)P0.001) and lactose ((*)P0.05) values with TT and CC genotypes, however no significant association of TT and CC genotypes with protein values was detected (P>0.05) and individuals with genotype TT had a superior milk yield in Sakiz sheep breeds. As sequence results, seven variation points were determined for exon 6 (g.185T>C) and 3'UTR (g.220G>A, g.229C>T, g.248C>T, g.250A>T, g.255T>C, g.258C>T) of the sheep POU1F1 gene. We have reported here for the first time single nucleotide polymorphisms of the POU1F1 gene for both exon 6 and 3'UTR and its effects on milk traits in Turkish sheep breeds were evaluated.